HSF1 Expression Research Articles

Heat shock transcription factor 1 facilitates liver cancer progression by driving super-enhancer-mediated transcription of MYCN.

Heat shock transcription factors (HSFs) play crucial roles in the development of malignancies. However, the specific roles of HSFs in hepatocellular carcinoma (HCC) have yet to be fully elucidated. To explore the involvement of the HSF family, particularly HSF1, in the progression and prognosis of HCC. We conducted a thorough analysis of HSF expression and copy number variations across various cancer datasets. Specifically focusing on HSF1, we examined its expression levels and prognostic implications in HCC. Invitro and invivo experiments were carried out to evaluate the impact of HSF1 on liver cancer cell proliferation. Additionally, we utilized CUT&Tag, H3K27 acetylation enrichment, and RNA sequencing (RNA-seq) to investigate the super-enhancer (SE) regulatory landscapes of HSF1 in liver cancer cell lines. HSF1 expression is elevated in HCC and is linked to poor prognosis in several datasets. HSF1 stimulates liver cancer cell proliferation both invitro and invivo, partly through modulation of H3K27ac levels, influencing enhancer distribution. Mechanistically, our findings demonstrate that HSF1 transcriptionally activates MYCN expression by binding to its promoter and SE elements, thereby promoting liver cancer cell proliferation. Moreover, increased MYCN expression was detected in HCC tumors and correlated with unfavorable patient outcomes. Our study sheds light on previously unexplored aspects of HSF1 biology, identifying it as a transcription factor capable of shaping the epigenetic landscape in the context of HCC. Given HSF1's potential as an epigenetic regulator, targeting the HSF1-MYCN axis could open up new therapeutic possibilities for HCC treatment. The HSF1-MYCN axis constitutes a transcription-dependent regulatory mechanism that may function as both a prognostic indicator and a promising therapeutic target in liver cancer. Further exploration of this axis could yield valuable insights into novel treatment strategies for HCC.

Comparative assessment of climate resilient potential in four poultry genotypes reared in hot-humid tropical environment: a preliminary evaluation.

The general objective of this study is to comparatively assess the climate-resilient potential of four different poultry genotypes-Giriraja (n = 8), Country chicken (n = 8), Naked neck (n = 8), and Kadaknath (n = 8)-reared in a hot-humid tropical environment. Birds from all genotypes had ad libitum access to feed and water and were exposed to identical environmental temperatures in the experimental shed. Diurnal meteorological data were recorded inside and outside the shed daily. Blood biochemical, hormonal, and endocrine variables were monitored monthly until the birds reached 12 weeks of age. Significant variations (P < 0.01) were observed at different intervals in variables, including total protein, albumin, globulin, triglycerides, and cholesterol. Genotype-specific differences were noted in triglycerides (P < 0.01), albumin (P < 0.01), total protein (P < 0.05), and cholesterol (P < 0.05). Inter-genotype variations (P < 0.05) were also observed in serum cortisol, T3, and T4 levels. Distinct variations (P < 0.05) were also observed during specific intervals, particularly in cortisol and T3 levels. The study of hepatic mRNA expression of HSPs and HSF-1 revealed a significant breed difference (P < 0.05) in the expression pattern of HSP60, HSP70, HSP90, and HSP110, while no difference was observed between genotypes for HSP40 and HSF-1. The study highlights the Naked Neck breed as an exemplar of resilience, showcasing its distinctive ability to maintain homeostasis under heat stress compared to other genotypes. The genetic and physiological insights gained from this investigation offer prospective pathways for aligning sustainable poultry farming with environmental exigencies.

Modulating responses of indicator genes in cellular homeostasis, immune defense and apoptotic process in the Macrophthalmus japonicus exposed to di(2-ethylhexyl) phthalate as a plastic additive

Di(2-ethylhexyl) phthalate (DEHP), have been increasingly used as plasticizers to manufacture soft and flexible materials and ubiquitously found in water and sediments in the aquatic ecosystem. The aim of the present study was to evaluate the effect of DEHP exposure on cellular homeostasis (HSF1 and seven HSPs), immune responses (ILF), and apoptotic responses (p53, BAX, Bcl-2). DEHP exposure upregulated the expression of HSF1 and ILF. Moreover, it altered the expression levels of HSPs (upregulation of HSP70, HSP90, HSP40, HSP83, and HSP67B2 and downregulation of HSP60 and HSP21) in conjunction with HSF1 and ILF in the gills and hepatopancreas of M. japonicus exposed to DEHP. At the protein level, DEHP exposure changed apoptotic signals in both tissues of M. japonicus. These findings indicate that chronic exposures to several DEHP concentrations could disturb cellular balance, damage the inflammatory and immune systems, and induce apoptotic cell death, thereby affecting the survival of M. japonicus.

Comprehensive analysis of human tissues reveals unique expression and localization patterns of HSF1 and HSF2.

Heat shock factors (HSFs) are the main transcriptional regulators of the evolutionarily conserved heat shock response. Beyond cell stress, several studies have demonstrated that HSFs also contribute to a vast variety of human pathologies, ranging from metabolic diseases to cancer and neurodegeneration. Despite their evident role in mitigating cellular perturbations, the functions of HSF1 and HSF2 in physiological proteostasis have remained inconclusive. Here, we analyzed a comprehensive selection of paraffin-embedded human tissue samples with immunohistochemistry. We demonstrate that both HSF1 and HSF2 display distinct expression and subcellular localization patterns in benign tissues. HSF1 localizes to the nucleus in all epithelial cell types, whereas nuclear expression of HSF2 was limited to only a few cell types, especially the spermatogonia and the urothelial umbrella cells. We observed a consistent and robust cytoplasmic expression of HSF2 across all studied smooth muscle and endothelial cells, including the smooth muscle cells surrounding the vasculature and the high endothelial venules in lymph nodes. Outstandingly, HSF2 localized specifically at cell-cell adhesion sites in a broad selection of tissue types, such as the cardiac muscle, liver, and epididymis. To the best of our knowledge, this is the first study to systematically describe the expression and localization patterns of HSF1 and HSF2 in benign human tissues. Thus, our work expands the biological landscape of these factors and creates the foundation for the identification of specific roles of HSF1 and HSF2 in normal physiological processes.

Glutamine Modulates Heat Shock Proteins, Endoplasmic Reticulum Stress and Cell Death in Rats with Thioacetamide-Induced Severe Acute Liver Failure

Severe Acute Liver Failure (SALF) is characterized by sudden dysfunction of liver cells in previously healthy persons without known underlying liver disease. Effective therapeutic approaches are necessary in an attempt to minimize the damage resulting from liver failure. Glutamine is considered to be an amino acid that plays many essential metabolic functions. This study was designed to evaluate the action of glutamine in protecting against cellular disturbances resulting from Thioacetamide (TAA)-induced SALF in rats. Two doses of thioacetamide (400 mg/kg) and 3 doses of glutamine (25 mg/kg) (ip) were administered. The experiment lasted 48 hours. Glutamine reduced blood levels of AST and ALT in TAA-treated rats. Histological evaluation indicated that glutamine acted in tissue protection by reducing the inflammatory infiltrate, ballooning and centrilobular necrosis induced by SALF, consequently restoring the hepatic parenchyma. Glutamine increased total protein levels and decreased carbonylated protein levels in the liver of SALF animals. Glutamine also acted by modulating HSF-1 and heat shock proteins expression, as well as by decreasing the expression of proteins involved in endoplasmic reticulum stress (GRP78, ATF6 and CHOP), and modifying the expression of apoptosis-related (Bcl -2, Bax and caspase 3) and autophagy-related (mTOR, Beclin1 and LC3α/β) proteins. These effects related to changes in PI3K, Akt and FOXO3a expression. Data obtained support a potential hepatoprotective role of glutamine in SALF.

Calycosin Enhances Heat Shock Related-Proteins in H9c2 Cells to Modulate Survival and Apoptosis against Heat Shock.

Heat shock proteins (HSPs), which function as chaperones, are activated in response to various environmental stressors. In addition to their role in diverse aspects of protein production, HSPs protect against harmful protein-related stressors. Calycosin exhibits numerous beneficial properties. This study aims to explore the protective effects of calycosin in the heart under heat shock and determine its underlying mechanism. H9c2 cells, western blot, TUNEL staining, flow cytometry, and immunofluorescence staining were used. The time-dependent effects of heat shock analyzed using western blot revealed increased HSP expression for up to 2[Formula: see text]h, followed by protein degradation after 4[Formula: see text]h. Hence, a heat shock damage duration of 4[Formula: see text]h was chosen for subsequent investigations. Calycosin administered post-heat shock demonstrated dose-dependent recovery of cell viability. Under heat shock conditions, calycosin prevented the apoptosis of H9c2 cells by upregulating HSPs, suppressing p-JNK, enhancing Bcl-2 activation, and inhibiting cleaved caspase 3. Calycosin also inhibited Fas/FasL expression and activated cell survival markers (p-PI3K, p-ERK, p-Akt), indicating their cytoprotective properties through PI3K/Akt activation and JNK inhibition. TUNEL staining and flow cytometry confirmed that calycosin reduced apoptosis. Moreover, calycosin reversed the inhibitory effects of quercetin on HSF1 and Hsp70 expression, illustrating its role in enhancing Hsp70 expression through HSF1 activation during heat shock. Immunofluorescence staining demonstrated HSF1 translocation to the nucleus following calycosin treatment, emphasizing its cytoprotective effects. In conclusion, calycosin exhibits pronounced protective effects against heat shock-induced damages by modulating HSP expression and regulating key signaling pathways to promote cell survival in H9c2 cells.

The beneficial effect of nanomethionine supplementation on growth performance, gene expression profile, and histopathology of heat-stressed broiler chicken

This study investigated the effects of nanomethionine (nano-meth) on performance, antioxidants, and gene expression of HSP70, HSP90 and Heat Shock factor-1 (HSF-1) from the liver, and TLR4 from the jejunum, of broiler chickens reared under normal temperatures or under heat stress. Three hundred 1-day-old chicks were randomly assigned to 5 treatment groups. Group 1 served as control. Under normal temperature, birds in group 2 received nano-meth (10 mL/L of drinking water) from d1 until the experiment ended. Group 3 birds were heat-stressed (HS) and did not receive any supplementation. Group 4 received nano-meth in the same dose from d1 old until experiment ended, and the birds were exposed to HS. Group 5 birds were HS and received supplementation of nano-meth during the HS period only. Nano-meth improved (P < 0.0001) final body weight, weight gain, feed conversion ratio, and also decreased (P < 0.0001) the effect of HS on growth performance. Reduction (P < 0.0001) in malondialdehyde and changes in antioxidant enzymes GPX and CAT activity indicated the antioxidant effect of nano-meth. Nano-meth supplementation caused an increase in the expression of HSP70 , HSP90 and HSF1, and a downregulation of TLR4 gene expression. Additionally, nano-meth-supplemented groups showed marked improvement in the histological liver structure, intestinal morphology and villus height compared to control or HS groups.

An Increase in HSF1 Expression Directs Human Mammary Epithelial Cells toward a Mesenchymal Phenotype.

HSF1 is a well-known heat shock protein expression regulator in response to stress. It also regulates processes important for growth, development or tumorigenesis. We studied the HSF1 influence on the phenotype of non-tumorigenic human mammary epithelial (MCF10A and MCF12A) and several triple-negative breast cancer cell lines. MCF10A and MCF12A differ in terms of HSF1 levels, morphology, growth in Matrigel, expression of epithelial (CDH1) and mesenchymal (VIM) markers (MCF10A are epithelial cells; MCF12A resemble mesenchymal cells). HSF1 down-regulation led to a reduced proliferation rate and spheroid formation in Matrigel by MCF10A cells. However, it did not affect MCF12A proliferation but led to CDH1 up-regulation and the formation of better organized spheroids. HSF1 overexpression in MCF10A resulted in reduced CDH1 and increased VIM expression and the acquisition of elongated fibroblast-like morphology. The above-mentioned results suggest that elevated levels of HSF1 may direct mammary epithelial cells toward a mesenchymal phenotype, while a lowering of HSF1 could reverse the mesenchymal phenotype to an epithelial one. Therefore, HSF1 may be involved in the remodeling of mammary gland architecture over the female lifetime. Moreover, HSF1 levels positively correlated with the invasive phenotype of triple-negative breast cancer cells, and their growth was inhibited by the HSF1 inhibitor DTHIB.

Involvement of the heat shock response (HSR) regulatory pathway in cadmium-elicited cerebral damage.

The heat shock response (HSR) is a cellular protective mechanism that is characterized by the induction of heat shock transcription factors (HSFs) and heat shock proteins (HSPs) in response to diverse cellular and environmental stressors, including cadmium (Cd). However, little is known about the relationship between the damaging effects of Cd and the HSR pathway in the chicken cerebrum following Cd exposure. To explore whether Cd exposure elicits cerebral damage and triggers the HSR pathway, chicks were exposed to Cd in the daily diet at different concentrations (35, 70, or 140mg/kg feed) for 90days, while a control group was fed the standard diet without Cd. Histopathological examination of cerebral tissue from Cd-exposed chickens showed neuronal damage, as evidenced by swelling and degeneration of neurons, loss of neurons, and capillary damage. Cd exposure significantly increased mRNA expression of HSF1, HSF2, and HSF3, and mRNA and protein expression of three major stress-inducible HSPs (HSP60, HSP70, and HSP90). Moreover, Cd exposure differentially modulated mRNA expression of small HSP (sHSPs), most notably reducing expression of HSP27 (HSPB1). Furthermore, Cd exposure increased TUNEL-positive neuronal apoptotic cells and up-regulated protein expression of caspase-1, caspase-8, caspase-3, and p53, leading to apoptosis. Taken together, these data demonstrate that activation of the HSR and apoptotic pathways by Cd exposure is involved in Cd-elicited cerebral damage in the chicken. Synopsis for the graphical abstract Cadmium (Cd)-induced neuronal damage triggers the heat shock response (HSR) by activating heat shock transcription factors (HSFs) and subsequent induction of major heat shock proteins (notably, HSP60, HSP70, and HSP90). Moreover, Cd exposure activates caspase-1, caspase-8, caspase-3, and p53 protein, thereby resulting in neuronal apoptosis in the chicken brain.

D-pinitol ameliorated H2O2-induced oxidative damage in PC12 cells and prolonged the lifespan by IIS pathway in Caenorhabditis elegans

D-pinitol (DP) has been extensively regarded as the main active component of legumes for anti-aging. In this study, we intended to explore the anti-aging mechanism of DP, utilizing computer modeling techniques. The results demonstrated that DP significantly delayed H2O2-induced cellular senescence. Model PC12 cells treated with DP exhibited increased cell viability, increased antioxidant enzyme activity (SOD, CAT), and reduced ROS and MDA levels. Furthermore, DP was discovered to have a positive effect on healthy longevity. In C. elegans, DP treatment enhanced lifespan, stress capacity, antioxidant capacity (T-SOD/CAT/GSH-Px/MDA/ROS), and altered aging-related indicators of lipofuscin accumulation, pharyngeal pump rate, motility, and reproduction. Moreover, DP could reduce the toxicity Aβ in transgenic C. elegans CL4176, CL2355, and CL2331. Further mechanistic studies indicated DP increased transcription factor (daf-16, skn-1, hsf-1) expression of insulin/insulin-like growth factor-1 signaling (IIS) pathway. As expected, DP also extended the downstream target genes of the three transcription factors (sod-3, ctl-1, ctl-2, gst-4, hsp-16.1, and hsp-16.2). Further mutant lifespan experiments, network pharmacology, and molecular docking revealed that DP might be life-extending through the IIS pathway. DP deserves extensive investigation and development as a potential anti-aging drug in the future.

HSF-1/miR-145-5p transcriptional axis enhances hyperthermic intraperitoneal chemotherapy efficacy on peritoneal ovarian carcinosis

Hyperthermic intraperitoneal administration of chemotherapy (HIPEC) increases local drug concentrations and reduces systemic side effects associated with prolonged adjuvant intraperitoneal exposure in patients affected by either peritoneal malignancies or metastatic diseases originating from gastric, colon, kidney, and ovarian primary tumors. Mechanistically, the anticancer effects of HIPEC have been poorly explored. Herein we documented that HIPEC treatment promoted miR-145-5p expression paired with a significant downregulation of its oncogenic target genes c-MYC, EGFR, OCT4, and MUC1 in a pilot cohort of patients with ovarian peritoneal metastatic lesions. RNA sequencing analyses of ovarian peritoneal metastatic nodules from HIPEC treated patients unveils HSF-1 as a transcriptional regulator factor of miR-145-5p expression. Notably, either depletion of HSF-1 expression or chemical inhibition of its transcriptional activity impaired miR-145-5p tumor suppressor activity and the response to cisplatin in ovarian cancer cell lines incubated at 42 °C. In aggregate, our findings highlight a novel transcriptional network involving HSF-1, miR145-5p, MYC, EGFR, MUC1, and OCT4 whose proper activity contributes to HIPEC anticancer efficacy in the treatment of ovarian metastatic peritoneal lesions.

Molecular, enzymatic responses and in vitro embryonic developmental competency of heat-shocked buffalo embryos co-cultured with granulosa cells monolayer

The present study was designed to establish a suitable alternative approach to mitigate the adverse effect of high culture temperature on in vitro embryo development and the related molecular response in buffalo. Pre-cultured granulosa cells (GCs) were used as a monolayer during in vitro embryo culture until day 8 (day of fertilization = D0). Post fertilization, presumptive embryos were randomly assigned into two culture conditions: embryos cultured in the presence of GCs monolayer under normal culture temperature (N: 38.5 °C; GEN group) or heat shock (H: 40.5 °C; GEH group) and their counterpart groups of embryos cultured without GCs (EN and EH groups). Additionally, two groups of GCs monolayer were cultured without embryos up to day 8 under 38.5 °C (GN) or 40.5 °C (GH) for further spent culture media enzymatic analyses. Heat shock was administered for the first 2 h of culture then continued at 38.5 °C until day 8. The results indicated that under heat treatment, GCs enhanced (P ≤ 0.05) embryo cleavage and development (day 8) rates, which were comparable to the embryos cultured at 38.5 °C. On the molecular level, blastocysts of the GEH group showed similar expressions of metabolism-regulating genes (CPT2 and SlC2A1/GLUT1) and an antioxidant gene (SOD2) when compared to the blastocysts of the EN group. The relative expression of HSP90 was significantly up-regulated under heat shock and/or co-culture conditions. However, HSF1 expression was increased (P ≤ 0.05) in the GEH group. No statistical differences were observed among the study groups for the pluripotency gene NANOG, and stress resistance transcript NFE2L2. Regarding the enzymatic profile, the concentrations of SOD, total protein, and MDA were decreased (P ≤ 0.05) in the GEH group compared to the cultured GCs without embryos (GH group). In conclusion, GCs as a monolayer have a beneficial impact on alleviating heat stress at the zygote stage through the regulatory mechanisms of metabolic activity, defense system, and heat shock response genes.

Bruceine F in Brucea Javanica Regulates Cellular STK3 and CK2A2 Targets to Correct Huntington Protein Misfolding in Mammalian Huntington’s Disease

Huntington’s disease is an autosomal dominant disorder characterized by progressive central nervous system degeneration characterized by motor, cognitive, and psychiatric disorders. This disease occurs frequently and is not easy to cure. We set out to investigate the pathogenesis of The Hippo pathway mediated by Brucea javanica in Huntington’s disease (HD) by studying the critical role of Brucea javanica in the pathogenesis of Huntington’s disease (HD) to provide a basis for the study of targeted drugs for this disease. Methods: Western blotting was used to rapidly determine YAP/TAZ activity and the expression level of HSF1 in tissues. YAP/TAZ activity and the expression level of HSF1 in tissues will show us the correct transcription level in the nucleus to measure efficacy. Hypothesis: Bruceine F in Brucea Javanica could effectively act on STK3 and CK2A2 targets to increase nuclear YAP activity and HSF1 expression, thus effectively treating Huntington’s disease. Possible Results: 1: Bruceine F does not act effectively on SYK3 and CK2A2 sites. There were no significant changes in YAP activity in either the nucleus or cytoplasm, as well as in STK3 and CK2A2 for all samples,the expression of HSF1 in tissues also did not change significantly. 2: Bruceine F successfully inhibited STK3, but activated CK2A2, and YAP activity was decreased in the cytoplasm and elevated in the nucleus. , HSF1 expression levels were decreased. 3:Bruceine F activated STK3 but inhibited CK2A2, and YAP activity was elevated in the cytoplasm and decreased in the nucleus. , HSF1 expression levels were elevated. 4: Bruceine F activated STK3 and CK2A2, and YAP activity was elevated in the cytoplasm and decreased in the nucleus. , HSF1 expression levels were reduced. 5:Bruceine F inhibited STK3 and CK2A2, YAP activity was decreased in the cytoplasm and increased in the nucleus, and HSF1 expression levels were increased. 6:Bruceine F activated CK2A2 in knockout STK3 mice, and YAP activity was unchanged in the cytoplasmic nucleus with reduced HSF1 expression. 7: Bruceine F inhibited CK2A2 in knockout STK3 mice, YAP activity was unchanged in the cytoplasmic nucleus, and HSF1 expression levels were elevated. 8: Bruceine F inhibited STK3 in knockout CK2A2 mice, and YAP activity was reduced in the cytoplasm and increased in the nucleus, while HSF1 expression levels remained unchanged. 9: Bruceine F activated STK3 in knockout CK2A2 mice, and YAP activity was increased in the cytoplasm and decreased in the nucleus, while HSF1 expression levels remained unchanged.

HSF-1 enhances cardioprotective potential of stem cells via exosome biogenesis and their miRNA cargo enrichment.

Stem cell therapy provides a hope to no option heart disease patient group. Stem cells work via different mechanisms of which paracrine mechanism is reported to justify most of the effects. Therefore, identifying the control arms for paracrine cocktail production is necessary to tailor stem cell functions in disease contextual manner. In this study, we describe a novel paracrine cocktail regulatory axis, in stem cells, to enhance their cardioprotective abilities. We identified that HSF1 knockout resulted in reduced cardiac regenerative abilities of mesenchymal stem cells (MSCs) while its overexpression had opposite effects. Altered exosome biognesis and their miRNA cargo enrichment were found to be underlying these altered regenerative abilities. Decreased production of exosomes by MSCs accompanied their loss of HSF1 and vice versa. Moreover, the exosomes derived from HSF1 depleted MSCs showed significantly reduced candidate miRNA expression (miR-145, miR-146, 199-3p, 199b and miR-590) compared to those obtained from HSF1 overexpressing MSCs. We further discovered that HSF1 mediates miRNAs' enrichment into exosomes via Y binding protein 1 (YBX1) and showed, by loss and gain of function strategies, that miRNAs' enrichment in mesenchymal stem cell derived exosomes is deregulated with altered YBX1 expression. It was finally demonstrated that absence of YBX1 in MSCs, with normal HSF1 expression, resulted in significant accumulation of candidate miRNAs into the cells. Together, our data shows that HSF1 plays a critical role in determining the regenerative potential of stem cells. HSF1 does that by affecting exosome biogenesis and miRNA cargo sorting via regulation of YBX1 gene expression.

Inflammatory responses of bovine endometrial epithelial cells are increased under in vitro heat stress conditions

Cattle exposed to heat stress have reduced fertility, reduced milk production and increased incidence of postpartum uterine infection. Heat stress is suggested to alter immune function of cattle; however, the mechanisms underlying heat stress mediated uterine infection are unknown. We hypothesized that exposure of endometrial cells to heat stress would further increase expression of inflammatory mediators in response to bacterial components due to altered heat-shock protein expression. Bovine endometrial epithelial cells (BEND) were exposed to Escherichia coli lipopolysaccharide (LPS) or a synthetic triacylated lipopeptide (Pam3CSK4) under heat stress (41.0 °C) or thermoneutral (38.5 °C) conditions for 24 h. Exposure of BEND cells to LPS or Pam3CSK4 increased the expression of the proinflammatory mediators IL1B, IL6, and CXCL8 compared to control medium. However, exposure of BEND cells to heat stress increased LPS and Pam3CSK4 induced expression of IL1B compared to cells exposed to thermoneutral conditions, and expression of LPS induced IL6 was also increased when BEND cells were exposed to heat stress. To determine if heat shock proteins increased BEND cell expression of inflammatory mediators, HSP1A1 and HSF1 were targeted by siRNA knock down. Expression of HSP1A1 and HSF1 were reduced following siRNA knockdown; however, knockdown of HSP1A1 or HSF1 further increased heat stress mediated increased expression of inflammatory mediators. These data suggest that heat stress increased BEND cell inflammatory responses to bacterial components, while heat shock proteins HSP1A1 and HSF1 help to restrain inflammatory responses. These mechanisms may contribute to the increased incidence of uterine infection observed in cows under heat stress conditions.

Regulation of antioxidant defense in response to heat stress in Siberian sturgeon (Acipenser baerii)

Siberian sturgeon (Acipenser baerii) is one of the most important breeding species of sturgeon in the world. The objective of the present study was to assess the effect of short-term gradual heating up (1 °C/8 h) and recovery changes on antioxidant defense systems in the liver, kidneys, gills, and serum of the Siberian sturgeon, and to examine related gene expression levels and histological changes in the liver and gills. When the water temperature reached to 33 °C (about 88 h), LOE (loss of equilibrium) appeared in individuals. Heat stress affected the metabolic mode and oxidative stress parameters in a tissue-dependent manner. Expression of HSP family genes such as heat shock cognate 70 (hsc70), heat shock protein 70 (hsp70), and heat shock protein 90 (hsp90) were elevated in the liver and gills of two heating groups, and these returned to normal levels after 24 h of recovery. Hsf1 expression was not significantly different between the control and heating groups, but was lower in the liver and higher in the gills after 24 h recovery. Heat stress resulted in clear histological changes in the liver, including the hepatic lobules, showing vacuolization and loss of cell boundaries and asymmetric shapes; the gills showing increasing numbers of vacuoles, thinning of basal cells, epithelial cell denaturation, degeneration, and necrosis. After 24 h of recovery, the liver and gills in the active group recovered better than those in the LOE group. Of four antioxidant enzymes (superoxidase dismutase (SOD), catalase (CAT), lactate dehydrogenase (LDH), glutathione peroxidase (GPX)), only LDH activity varied significantly, decreasing in the liver, increasing in the kidneys of heating groups, and recovering to control levels after 24 h. Total antioxidant capacity (T-AOC) also did not change significantly in the three tissues. Both plasma cortisol and lactate were significantly influenced by thermal stress, and returned to control levels within 24 h. MDA (malondialdehyde) remained at a relatively stable level after heat stress and recovery. Rapid cooling after enduring heat stress allowed the Siberian sturgeon to recover quickly. After 24 h of recovery, nine LOE and eleven active recovery individuals were alive and able to feed, accounting for 32.7% and 36.5% of the experimental groups, respectively. These results indicate that Siberian sturgeon not only has a strong antioxidant system and adaptive capacity to short-term gradual heating, but also has the capacity to quickly recover from heat stress, with physiological parameters returning to pre-stress levels after 24 h.

수온 스트레스에 의한 명태의 Heat Shock Factor 1의 분자생물학적 특성과 Heat Shock Protein 70의 단백질 발현 패턴

This study evaluated the levels of mRNA expression of HSF1 and HSP70 expression patterns in walleye pollock, Gasus chalcogrammus according to water temperature. Walleye pollack HSF1, which has not been reported, was used as a Rapid Amplification of cDNA Ends (RACE)-PCR strategy. The HSF1 amino acid sequence of walleye pollack showed 93% identification with the Atlantic cod. On the other hand, it showed relatively low identification with 50% in zebrafish. However, in the phylogenetic analysis, fish HSF1 formed a single clade group. The relative mRNA expression of HSF1 in the liver, intestine, gill, kidney, and heart of juveniles and immatures was investigated. The tissues in juvenile and immature, HSF1 mRNA expression was the highest at 14℃, and HSF1 mRNA levels increased significantly from 11℃ compared to 5 and 8℃. The mRNA levels of HSF1 were particularly high in the gill both juveniles and immatures. The expression of HSP70 was also evident in 11℃ and 14℃. These results indicate that water temperature of 11°C or higher is exposed to stressed-condition in walleye pollock. Therefore, HSF1 and HSP70 can be considered as important indicator for water temperature stress in walleye pollock.

The effect of progressive endurance training and extract of black winter truffle on proteins levels and expression of hippocampus α-synuclein and HSF1 in the healthy and diabetic rats

AimThe research aimed to investigate the effect of endurance running and T. Brumale extract on α-Syn and HSF1 in the brain and serum of healthy and diabetic rats. MethodsA total of 40 Wistar rats were randomly divided into eight groups: Control (C), Exercise (E), Control-Tuber (T), Exercise-Tuber (ET), Control-Diabetes (D), Exercise-Diabetes (ED), Control-Diabetes-Tuber (CDT), and Exercise-Diabetes-Tuber (EDT). The endurance running was carried out five times per week for five weeks. The hippocampus and the serum α-Syn and HSF1 were measured using an enzyme-linked immunosorbent assay method. ResultsThe brain α-Syn levels were higher in diabetic groups than in the healthy groups, but insignificantly (P ≤ 0.05). The brain α-Syn level significantly increased in the EDT group compared to the T group (P ≤ 0.05). The serum level of α-Syn in the ED group was significantly higher than in the E and D groups (P ≤ 0.05). The brain HSF1 level was significantly higher in the ED group compared to the D group (P ≤ 0.05). The gene expression of hsf1 was significantly reduced in the E group compared to the other groups and the EDT group compared to ED and CDT groups (P ≤ 0.05). Furthermore, the serum HSF1 level significantly increased in the ED group compared to the D group (P ≤ 0.05). ConclusionThe results of this study suggest that progressive endurance running may improve neuroprotective conditions in diabetic patients by increasing HSF1 in the brain.

Acute effects of a single moderate-intensity exercise bout performed in fast or fed states on cell metabolism and signaling: Comparison between lean and obese rats

AimsAlthough the benefits of exercise can be potentiated by fasting in healthy subjects, few studies evaluated the effects of this intervention on the metabolism of obese subjects. This study investigated the immediate effects of a single moderate-intensity exercise bout performed in fast or fed states on the metabolism of gastrocnemius and soleus of lean and obese rats. Main methodsMale rats received a high-fat diet (HFD) for twelve weeks to induce obesity or were fed standard diet (SD). After this period, the animals were subdivided in groups: fed and rest (FER), fed and exercise (30 min treadmill, FEE), 8 h fasted and rest (FAR) and fasted and exercise (FAE). Muscle samples were used to investigate the oxidative capacity and gene expression of AMPK, PGC1α, SIRT1, HSF1 and HSP70. Key findingsIn relation to lean animals, obese animals' gastrocnemius glycogen decreased 60 %, triglycerides increased 31 %; glucose and alanine oxidation decreased 26 % and 38 %, respectively; in soleus, triglycerides reduced 46 % and glucose oxidation decreased 37 %. Exercise and fasting induced different effects in glycolytic and oxidative muscles of obese rats. In soleus, fasting exercise spared glycogen and increased palmitate oxidation, while in gastrocnemius, glucose oxidation increased. In obese animals' gastrocnemius, AMPK expression decreased 29 % and SIRT1 increased 28 % in relation to lean. The AMPK response was more sensitive to exercise and fasting in lean than obese rats. SignificanceExercise and fasting induced different effects on the metabolism of glycolytic and oxidative muscles of obese rats that can promote health benefits in these animals.

L-Theanine attenuates heat stress-induced proteotoxicity and alterations in carbohydrate and lipid metabolism via heat shock factor 1.

Extreme heat caused by global warming accelerated the frequency of heat stress (HS). Proteotoxic stress induced by the aggregation of misfolded proteins and metabolic stress triggered by alterations in the metabolism were observed during HS. The activation of heat shock factor 1 (Hsf1) and its interaction with adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPK) are critical in addressing proteotoxicity and metabolic stress in heat-stressed organisms. Previous studies have shown that L-theanine (LTA) can regulate nutrient metabolism through the AMPK pathway and can alleviate HS. Therefore, we hypothesize that LTA may help in restoring homeostasis by regulating nutrient metabolism under HS. Here, we investigated the effects of LTA on nutrient metabolism in heat-stressed rats and characterized the underlying mechanisms using RNA sequencing and metabonomics. The results showed that LTA alleviated HS-induced liver damage, promoted body weight gain, decreased serum cortisol and enhanced the total protein content. Besides, it regulated the expression of genes related to carbohydrate, lipid and amino acid metabolism and altered metabolite levels. Moreover, LTA inhibited the expression of Hsf1 and heat shock protein 70 (Hsp70), promoted AMPK phosphorylation and the expression of glucose-6-phosphatase catalytic subunit 1 (G6pc), and inhibited the phosphorylation of acetyl-CoA carboxylase 1 (ACC1) in heat-stressed rats. Mechanistically, LTA alleviated HS-induced proteotoxic stress by acting on Hsf1/Hsp70; simultaneously, it promoted AMPK phosphorylation by suppressing Hsf1 expression, which in turn inhibited fatty acid synthesis and hepatic gluconeogenesis, thus alleviating HS-induced metabolic stress. These results suggest that LTA regulates nutrient metabolism through Hsf1/AMPK and alleviates HS-induced proteotoxicity via Hsf1/Hsp70.