Levels Of Heat Shock Protein Research Articles

P2Y6 receptor-mediated signaling amplifies TLR-induced pro-inflammatory responses in microglia.

TLR-induced signaling initiates inflammatory responses in cells of the innate immune system. These responses are amongst others characterized by the secretion of high levels of pro-inflammatory cytokines, which are tightly regulated and adapted to the microenvironment. Purinergic receptors are powerful modulators of TLR-induced responses, and we here characterized the effects of P2Y6 receptor (P2RY6)-mediated signaling on TLR responses of rhesus macaque primary bone marrow-derived macrophages (BMDM) and microglia, using the selective P2RY6 antagonist MRS2578. We demonstrate that P2RY6-mediated signaling enhances the levels of TLR-induced pro-inflammatory cytokines in microglia in particular. TLR1, 2, 4, 5 and 8-induced responses were all enhanced in microglia, whereas such effects were much less pronounced in BMDM from the same donors. Transcriptome analysis revealed that the overall contribution of P2RY6-mediated signaling to TLR-induced responses in microglia leads to an amplification of pro-inflammatory responses. Detailed target gene analysis predicts that P2RY6-mediated signaling regulates the expression of these genes via modulation of the activity of transcription factors NFAT, IRF and NF-κB. Interestingly, we found that the expression levels of heat shock proteins were strongly induced by inhibition of P2RY6-mediated signaling, both under homeostatic conditions as well as after TLR engagement. Together, our results shed new lights on the specific pro-inflammatory contribution of P2RY6-mediated signaling in neuroinflammation, which might open novel avenues to control brain inflammatory responses.

Prenatal thermal stress affects acute-phase proteins, heat shock protein 70, and circulating corticosterone in developing broiler embryos and neonates

Higher or lower incubation temperature may impose some degree of stress on developing poultry embryos. This study was designed to delineate the effects of prenatal thermal stress on serum levels of acute-phase proteins (APPs), namely ceruloplasmin (CPN) and alpha-1-acid glycoprotein (AGP), the regulation of brain mRNA levels of heat shock protein (Hsp) 70, and serum levels of corticosterone (CORT) in embryos and neonatal chicks. Hatching eggs were subjected to three thermal treatments; (i) standard optimum temperature throughout (SS: 37.8 °C and 56 % RH), (ii) heat stress for 12 h daily (HS: 40.0 °C and 56 % RH), and (iii) cold stress for 12 h daily 18 (CS: 30.2 °C and 56 % RH). The heat and cold stress treatments were imposed from the 10th to the 18th day of incubation (ED). Results showed that thermal stress had a negligible effect on hatchability rate and body temperatures of neonatal chicks. The CS treatment was detrimental to embryonic growth. The HS treatment elevated AGP (ED 16, ED 18, and post-hatch day 1), CPN (on post-hatch day 1), and CORT (ED 14). On the contrary, the CS embryos had reduced AGP (ED14, ED16, ED18, and post-hatch day 1), CPN (ED 16), and CORT (ED 14, ED 16, ED 18). The brain mRNA levels of Hsp70 were upregulated throughout the experimental period in both the HS and CS embryos and chicks. Based on these modifications, AGP, together with Hsp70 mRNA expression, could be considered effective biomarkers useful to evaluate the magnitude and the time response of embryos and neonatal chicks to prenatal thermal stress. It is concluded that developing chicken embryos have the ability to evoke APPs, Hsp70 and CORT reactions which are important to cope with thermal stress.

Exercise-induced FKBP8-mediated Mitophagy Via AMPK Activation In Soleus Muscle Of Rats

Scientific Abstract PURPOSE: To investigate the effects of downhill running on mitochondrial structure/function and expression levels of mitophagy-related proteins in rat skeletal muscle, and whether AMP-activated protein kinase (AMPK) plays a regulatory role in this context. METHODS: Male Sprague-Dawley rats were divided into a control (C, n = 8) or an exercise (E, n = 56) group. Rats in the E group were exercised on a treadmill down a 16° incline at 16 m/min for 90 min, and were further divided into 0 h (E0), 12 h (E12), 24 h (E24), 48 h (E48) and 72 h (E72) post-exercise sub-groups. Rats in the E0 and E12 sub-groups received acute AMPK agonist AICAR treatment (500 mg/kg via I.P.) or saline (n = 8 each) 30 min before exercise. At each time point the soleus muscle was collected under full anesthesia. Mitochondrial ultrastructural changes in skeletal muscle were observed by using a transmission electron microscope. Protein expression levels of skeletal muscle p-AMPKα1/2(T172), total AMPKα, heat shock protein 60 (HSP60), cyclophilin D (CypD), mitochondrial FK506 binding protein 8 (FKBP8/FKBP38), microtubule-associated protein 1 light chain 3 (LC3) and cytosolic cytochrome C (Cyt C) were determined by using Western blot. LC3 co-localizations with mitochondria and FKBP8 were measured by the immunofluorescence technique. One-way and two-way ANOVAs were used for data analysis. RESULTS: After downhill running, skeletal muscle mitochondrial structure appeared to be abnormal and contained a large number of mitophagosomes; the expression levels of AMPK phosphorylation (E12 = 1.81 ± 0.54), FKBP8 (E12 = 3.11 ± 0.26), LC3 (E12 = 1.80 ± 0.12), CypD (E0 = 1.41 ± 0.26) and Cyt C (E0 = 2.31 ± 0.68) and the co-localization of FKBP8 and LC3 were significantly higher, whereas the expression levels of mitochondrial quantitative protein HSP60 (E12 = 0.62 ± 0.09) were significantly lower than those in the C group (p < 0.05 to p < 0.01). AICAR treatment enhanced AMPK phosphorylation in exercised muscle and the expression levels of mitochondrial FKBP8 and LC3 involved in mitophagy. CONCLUSION: A session of downhill running activated the AMPK phosphorylation and LC3 co-localizations with mitochondria and FKBP8, and induced mitophagy and mitochondrial damage within rat skeletal muscle. (Supported by Natural Science Foundation of China grant 31900842).

Profile of Serum Heat Shock Protein-27 Level in Patients with Salivary Gland Tumor.

Heat shock protein 27 (HSP27) plays important roles in many cellular processes and has been implicated in different types of diseases such as cancers. This study aimed to evaluate the serum level of HSP27 in patients with salivary gland tumors and to determine its possible correlation with the prognosis of the disease. This cross-sectional study was performed on 60 patients with sali-vary gland tumor including 16 pleomorphic adenoma, 33 adenoid cystic carcinoma, 6 mu-coepidermoid carcinoma, 5 acinic cell carcinoma, and 28 healthy control subjects. The con-trol cases were healthy blood donors who matched the study group in age and sex. Serum samples were obtained from the clotted blood and HSP27concentrations were measured with sandwich enzyme-linked immunosorbent assay (ELISA). Statistical analysis was performed by using one-way ANOVA, post Hoc test, independent sample t-test, and ROC analysis. A p value of less than 0.05 was considered as significant. The mean serum level of HSP27 was 3956.1±3830.1 (pg/ml) in patients with malig-nant salivary gland tumor, which was significantly higher than that in benign salivary gland tumor (752.2±485.6) and healthy controls (602.3±575.8) (p <0.001). However, there was no significant difference in the HSP27 serum levels between the patients with benign salivary gland tumors and healthy controls (p= 0.2). No association was detected between the mean serum levels of HSP27 and clinicopathologic factors such as age, sex, stage and nodal metas-tasis (p > 0.05), except for the tumor size (p= 0.04). The HSP27 concentration increased in patients with malignant salivary gland tumors. Moreover, the HSP27 level was correlated with tumor growth, invasiveness, and diagnosability. Yet, larger clinical studies are required to explore its prognostic value.

A chromosome-level genome assembly provides insights into the environmental adaptability and outbreaks of Chlorops oryzae

Chlorops oryzae is a pest of rice that has caused severe damage to crops in major rice-growing areas in recent years. We generated a 447.60 Mb high-quality chromosome-level genome with contig and scaffold N50 values of 1.17 Mb and 117.57 Mb, respectively. Hi-C analysis anchored 93.22% scaffolds to 4 chromosomes. The relatively high expression level of Heat Shock Proteins (HSPs) and antioxidant genes in response to thermal stress suggests these genes may play a role in the environmental adaptability of C. oryzae. The identification of multiple pathways that regulate reproductive development (juvenile hormone, 20-hydroxyecdsone, and insulin signaling pathways) provides evidence that these pathways also play an important role in vitellogenesis and thus insect population maintenance. These findings identify possible reasons for the increased frequency of outbreaks of C. oryzae in recent years. Our chromosome-level genome assembly may provide a basis for further genetic studies of C. oryzae, and promote the development of novel, sustainable strategies to control this pest.

Effect of chilling rate on heat shock proteins abundance, myofibrils degradation and caspase‐3 activity in postmortem muscles

SummaryThe objective of this study was to investigate the effect of chilling rate on heat shock proteins (HSP) abundance, myofibrillar proteins degradation and caspase‐3 activity of lamb muscle in postmortem. Eighteen longissimus dorsi (LD) muscles from lamb were treated under three different chilling rates—very fast chilling I (VFC‐I, 22.2 °C h−1), very fast chilling II (VFC‐II, 32.4 °C h−1) and control (1.44 °C h−1)—and stored at −1 °C, −1 °C and 4 °C for 120 h postmortem, respectively. The results showed that myofibril fragmentation index (MFI), the abundance of αβ‐crystallin and HSP20, as well as the degradation of HSP27, HSP70, troponin‐T and desmin under the VFC‐I and VFC‐II groups were higher than control. Notably, HSP90 abundance may not be affected by the chilling rate in the late postmortem aging. Additionally, with increasing of chilling rate for postmortem muscle could inhibit caspase‐3 activity. Overall, results indicated that chilling rate may affect the process of meat tenderization by changing the abundance levels of heat shock proteins, myofibrillar degradation and apoptotic pathway.

Heat Shock Protein 70 Mediates the Protective Effect of Naringenin on High-Glucose-Induced Alterations of Endothelial Function.

Endothelial dysfunction plays a pivotal role in the development and progression of diabetic vascular complications. Naringenin (Nar) is a flavanone bioactive isolated from citrus fruits known to have in vitro and in vivo antidiabetic properties. However, whether Nar affects endothelial function remains unclear in diabetes or under high-glucose (HG) condition. Using an in vitro model of hyperglycemia in human umbilical vein endothelial cells (HUVECs), we found that Nar administration markedly attenuated HG-induced alterations of endothelial function, evidenced by the mitigation of oxidative stress and inflammation, the reduction of cell adhesion molecular expressions, and the improvement of insulin resistance. We also found that HG exposure significantly reduced the levels of intracellular heat shock protein 70 (iHSP70 or iHSPA1A) and the release of HSP70 from HUVECs. HSP70 depletion mimicked and clearly diminished the protective effects of Nar on HG-induced alterations of endothelial function. In addition, Nar treatment significantly enhanced iHSP70 protein levels through a transcription-dependent manner. These results demonstrated that Nar could protect HUVECs against HG-induced alterations of endothelial function through upregulating iHSP70 protein levels. These findings are also helpful in providing new therapeutic strategies that are promising in the clinical use of Nar for the treatment of diabetes and diabetic complications.

Vitamin C (Ascorbic acid) protects from neuropathy caused by cisplatin, through enhanced heat shock protein-70 and reduced oxidant effect

SUMMARYOBJECTIVE:We aimed to determine whether vitamin C has a protective effect on cisplatin-induced neuropathy in rats.METHODS:In total, 24 rats were included in the study of which 8 rats (no drug administered) were categorized as the control group. The remaining 16 rats were given a total dose of 20 mg/kg cisplatin to induce neuropathy. These drug-administered rats (16 rats) were randomly divided into two groups, namely, group-1 (n=8): cisplatin+saline and group-2 (n=8): cisplatin+vitamin C (500 mg/kg/day). All rats were tested for motor function and electromyographic activity 3 days after cisplatin. Motor performance was evaluated by an inclined-plane test. Compound muscle action potential was evaluated. Plasma malondialdehyde, glutathione, tumor necrosis factor-α, interleukin 6, and sciatic nerve HSP 70 levels were measured. Axon diameter and nerve growth factor expression levels were analyzed.RESULTS:Plasma malondialdehyde, tumor necrosis factor-α, and interleukin 6 levels were higher in the cisplatin+saline group than control group (p<0.001). But vitamin C significantly reduced malondialdehyde and inflammatory cytokine levels when compared with the cisplatin+saline group (p<0.001). Glutathione levels were lower in both cisplatin+saline and cisplatin+vitamin C groups than control group, but vitamin C significantly ameliorated the glutathione levels (p<0.05). Sciatic heat shock protein-70 levels were significantly higher in the cisplatin+vitamin C group than cisplatin+saline group. Compound muscle action potential amplitude and inclined plane test scores were significantly improved in the vitamin C group (p<0.05). Axon diameter and nerve growth factor expression ameliorated with vitamin C (p<0.05).CONCLUSIONS:We demonstrated the ameliorated effects of vitamin C on cisplatin-induced neuropathy through increased heat shock protein-70, nerve growth factor levels, and reduced inflammatory and oxidant effects. The results are promising to improve the neurotoxic effects of cisplatin in cancer patients.

Acute ammonia stress-induced oxidative and heat shock responses modulated by transcription factors in Litopenaeus vannamei

The present study aimed to examine the effects of short-term exposure to ammonia on stress and oxidative responses in shrimp (Litopenaeus vannamei) and to determine whether the antioxidant system related to the regulatory role of transcription factors and stress proteins was activated. Shrimp were exposed ammonia-N at four concentrations: 0 (control), 5, 10, and 15 mg/L, for 48 h. The hepatopancreas was sampled to measure the levels of glutathione (GSH), malondialdehyde (MDA), nitric oxide (NO); the activities of superoxide dismutase (SOD), catalase (CAT), nitric oxide synthase (NOS); and the expression levels of GSH-px (encoding glutathione peroxidase), GST (encoding glutathione-S-transferase), HSP70 (encoding heat shock protein 70), HSP90 (encoding heat shock protein 90), p53, RELISH, and AKIRIN. We observed that exposure to a high ammonia content increased the abundance of oxidative factors (MDA, CAT, SOD, NOS, and NO), reduced the levels of GSH, and upregulated the mRNA expression levels of antioxidant genes (GSH-px and GST), stress-related genes (HSP70 and HSP90), and transcription factor genes (p53, RELISH, and AKIRIN). These results indicated that ammonia induced oxidative stress and inflammation. Both enzymatic and nonenzymatic antioxidant defense systems are involved, which might be regulated by HSPs, as well as certain transcription factors, such as p53 and nuclear factor kappa B (NF-κB), thus mounting an adaptive response to help rebalance redox homoeostasis.

The Effect of Global Warming on Complex Disorders (Mental Disorders, Primary Hypertension, and Type 2 Diabetes).

Multiple studies imply a strong relationship between global warming (GW) and complex disorders. This review summarizes such reports concentrating on three disorders—mental disorders (MD), primary hypertension, and type 2 diabetes (T2D). We also attempt to point at potential mechanisms mediating the effect of GW on these disorders. Concerning mental disorders, immediate candidates are brain levels of heat-shock proteins (HSPs). In addition, given that heat stress increases reactive oxygen species (ROS) levels which may lead to blood–brain barrier (BBB) breakdown and, hence, enhanced protein extravasation in the brain, this might finally cause, or exacerbate mental health. As for hypertension, since its causes are incompletely understood, the mechanism(s) by which heat exposure affects blood pressure (BP) is an open question. Since the kidneys participate in regulating blood volume and BP they are considered as a site of heat-associated disease, hence, we discuss hyperosmolarity as a potential mediator. In addition, we relate to autoimmunity, inflammation, sodium excretion, and HSP70 as risk factors that might play a role in the effect of heat on hypertension. In the case of T2D, we raise two potential mediators of the effect of exposure to ambient hot environment on the disease’s incidence—brown adipose tissue metabolism and HSPs.

The circulating 70 kDa heat shock protein (HSPA1A) level is a potential biomarker for breast carcinoma and its progression

The early diagnosis of breast cancer can improve treatment and prognosis. We sought to evaluate whether the serum concentration of the 70 kDa heat shock protein (HSPA1A) was elevated in Brazilian women with breast cancer, and if levels correlated with tumor characteristics. This was a cross-sectional, analytical, case–control exploratory study performed at The University of São Paulo School of Medicine. From September 2017 to December 2018, 68 women with breast cancer and 59 controls were recruited. The HSPA1A concentration in serum samples was determined by ELISA by individuals blinded to the clinical data. The mean ages in the study and control groups were 54.9 and 52.0 years, respectively. The median serum levels of HSPA1A were elevated in women with breast cancer (1037 pg/ml) compared with controls (300 pg/ml) (p < 0.001). Elevated HSPA1A levels were associated with advanced histological tumor grade (p < 0.001) and with the cell proliferation index (KI67) (p = 0.0418). The HSPA1A concentration was similar in women with different histological subtypes, nuclear grade, hormone receptor expression, HER2 status and the presence or absence of angiolymphatic invasion. Elevated serum HSPA1A in Brazilian women with advanced histological grade and proliferation index breast cancer supports the potential value of additional investigation on larger and more varied populations to verify the value of HSPA1A detection as a component of breast cancer diagnosis and progression.

Sustained high body temperature exacerbates cognitive function and Alzheimer’s disease-related pathologies

Global warming is a serious public health threat to people worldwide. High body temperature is one of the important risk factors for Alzheimer’s disease (AD), and the body temperature of AD patients has been found to be significantly higher than that of elderly control subjects. However, the effects of high body temperature on cognitive function and AD pathologies have not been completely elucidated. We report here that Tg2576 mice housed at a high ambient temperature of 30 °C for 13 months showed an increase in the body temperature, which is accompanied by memory impairment and an enhancement of amyloid-β peptides (Aβ) generation through the upregulation of β-site APP cleaving enzyme 1 (BACE1) level and decrease in the level of an Aβ-degrading enzyme, neprilysin (NEP) in the brain, compared with those of Tg2576 mice at 23 °C. High body temperature also increased the levels of heat shock proteins (HSPs), stress-stimulated kinases such as JNK, and total tau, leading to the enhancement of tau phosphorylation at 30 °C. Taken together, our findings suggest that high body temperature exacerbates cognitive function and AD pathologies, which provides a mechanistic insight for its prevention.

Inducible Heat Shock Protein 70 Levels in Patients and the mdx Mouse Affirm Regulation during Skeletal Muscle Regeneration in Muscular Dystrophy.

Stress-inducible heat shock protein 70 (HSP70) is both a protective chaperone involved in protein homeostasis and an immune regulator. In both capacities, HSP70 has been implicated in muscle disorders, yet with fragmented and differing results. In this study we aimed to compare results obtained in the mouse model for the severest form of muscular dystrophy (MD) equivalent to Duchenne MD, termed the mdx mouse, with results obtained in human MD. Skeletal muscle and serum samples were obtained from 11 healthy controls, 11 fully characterized patients diagnosed with Becker MD and limb girdle MD (LGMD), and six muscle disease controls. In addition, muscle extracts were prepared from tibialis anterior of mdx and control mice at ages 4, 8 and 12 weeks. The HSP70 levels were quantified using RT-PCR, western blotting and protein arrays, and localized in muscle tissue sections using double immunofluorescence. We found selective and significant 2.2-fold upregulation of HSP70 protein in mdx tibialis muscle at the earliest disease phase only. In LGMD and Becker MD patients, HSP70 protein levels were not significantly different from those of healthy muscle and serum. HSP70 was localized to regenerating muscle fibers both in mouse and human MD skeletal muscle tissues. Toll-like receptor (TLR) 2 and TLR4 expression was moderately increased on the sarcolemma in MD muscle, yet protein levels were not significantly different from normal controls. HSP70 upregulation in MD appears disease stage-dependent, marking the phase of most active muscle regeneration in the mdx mouse. We postulate that well-timed supportive therapeutic interventions with HSP70 agonists could potentially improve muscle tissue's regenerative capacities in MD, attenuating loss of muscle mass while we await gene therapies to become more widely available.

7-aminocephalosporanic acid, a novel HSP90β inhibitor, attenuates HFD-induced hepatic steatosis

Hepatic steatosis is one of the most important causes of liver disease worldwide. Heat shock protein 90 (HSP90) is essential for numerous client proteins. Recently, more attention was focused on increased HSP90 levels in hepatic steatosis, especially HSP90β. Thus, great efforts have been made to develop HSP90β inhibitors, and most natural inhibitors are derived from microorganisms. In this study, using microarray chips and surface pasmon resonance (SPR) technology, we screened 189 antibiotics in order to obtain an inhibitor directly binding to the non-N-terminal domain of HSP90β. Finally, we discovered an antibiotic, 7-aminocephalosporanic acid (7ACA), with a KD value of 6.201 μM between 7ACA and non-N-terminal domain of HSP90β. Besides, 7ACA was predicted to interact with the middle domain (MD) of HSP90β. In HepG2 cells, we found that 7ACA reduced cellular total cholesterol (TC) and triglyceride (TG) by decreasing sterol regulatory element-binding proteins (SREBPs). In HFD fed mice, administration of 7ACA (5, 10, and 25 mg kg−1 d−1, ig, for 12 weeks) dose-dependently decreased serum TC and TG and played an important role in protecting liver and adipose tissue from lipid accumulation. In conclusion, our study demonstrated that antibiotic 7ACA, as an HSP90β middle domain inhibitor, was promising for the development of lipid-lowering drugs.

The oxidized cellooligosaccharides confer thermotolerance in Arabidopsis by priming ethylene via heat shock factor A2.

Global climate change, especially heatwaves and aridity, is a major threat to agricultural production and food security. This requires common efforts from the scientific community to find effective solutions to better understand and protect the plant's vulnerabilities to high temperatures. The current study demonstrates the potential of cellooligosaccharides (COS), which are native and oxidized signaling molecules released by lytic polysaccharide monooxygenases (LPMO) enzymes during cell wall degradation by microbial pathogens. The extracellular perception of COS leads to the activation of damage-triggered immunity, often protecting the plant against biotic stress. However, how these signaling molecules affect abiotic stress tolerance is poorly understood. Here, we show that native COS and oxidized COS (oxiCOS) perception increase the transcript levels of several HEAT SHOCK FACTORS (HSFs) and HEAT SHOCK PROTEINS (HSPs) genes in Arabidopsis plants. However, only oxiCOS treatment triggers ethylene priming and increases thermotolerance. Furthermore, the function of the transcription factor HSFA2 is required for these processes. Altogether, our results indicate that the perception of Damage-Associated Molecular Patterns (DAMPs) may improve tolerance to adverse abiotic conditions, like exposure to high temperatures.

Gossypin'in farklı kanser hücre dizilerinde HSP60 ve HSP70'in gen ekspresyonu üzerindeki etkisi

Purpose: The aim of this study is to evaluate the impact of gossypin on the expression level of heat shock proteins (HSPs) genes in different cancer cells.&#x0D; Materials and Methods: Cells were grown under standard culture conditions. Cancer cells were treated with different concentrations (5-100 µg/ml) of gossypin and cisplatin (50 µM) as positive control. Cell viability and effective dose range (5-100 µg/ml) of gossypin were determined by MTT at 24, 48 and 72 hours. After RNA isolation and cDNA synthesis, HSP60 and HSP70 gene expression levels were analyzed using RT-PCR. For gene expression analysis, the 2-∆∆ct method was used.&#x0D; Results: According to the MTT results, 25-50-100 µg/ml of gossypin doses were found effective on HSP60 and HSP70 gene expression levels in the cancer cell lines. Gossypin affected with dose-dependently the expression of HSP60 and HSP70 in the three cell lines. In the three cell lines, 50 µg/ml and 100 µg/ml of gossypin doses significantly reduced the expression of HSP60 and HSP70 compared to control group.&#x0D; Conclusion: Our results strongly supported the anticarcinogenic effect of gossypin at various doses in different cell lines. However, we believe that further in vivo research and human studies are needed. Our findings suggest that gossypin could be suitable candidate agent for further investigation to develop new strategies for the prevention and/or treatment of different cancer types.

Assessment of Serum Levels of Oxidative Stress Markers and Heat Shock Proteins in Myocardial Infraction Patients

Introduction: Heat stress proteins also known as shock proteins are the molecular chaperones due to various stimuli response to heat and ischemic injury to the cells. They are important in folding and degradation of other proteins involved in genesis of cardiovascular pathologies. Objectives: The main aim is to upgrade the role of oxidative markers and these stress proteins not only in development but also in evolution related to heart disease. Material and methods: Subjects were selected as diagnosed myocardial infarction in Faisalabad institute of cardiology, Faisalabad Division, Punjab. All subjects were further categorized as risk group and non-risk group on the basis of their risk factors history using ACC/AHC 2017 guided criteria for detection of myocardial infarction included chest pain, ECG finding and cardiac enzymes. Results: Data clearly depicts the demographical and hematological profile i-e complete blood picture of patients with diagnosed myocardial infraction and control subject. Hemoglobin as a highly advanced allosteric protein present in the form of HbA with two α and two β chains while globin chains are synthesized in erythrocytes cytosol. Conclusion: Despite of increasing evidence from the recent data, it is recommended that functions of these heat shock proteins related to guard cells against programmed apoptosis from stressful aspects e.g. infection, mechanical stress, oxidized low density lipoprotein and oxidants are also known as stress proteins. Keywords: Stress Proteins, Atherosclerosis, Apoptosis, Myocardial Infarction, Oxidative Markers

Exercise‐induced histone H3 trimethylation at lysine 27 facilitates the adaptation of skeletal muscle to exercise in mice

Histone H3 trimethylation at lysine 27 (H3K27me3) is known to act as a transcriptionally repressive histone modification via heterochromatin formation. In skeletal muscle, it was also reported that H3K27me3 was enriched at the sites transcriptionally activated by exercise, although the role of H3K27me3 in adaptation to exercise is unknown. In this study, using mouse tibialis anterior muscle, we initially determined the genome-wide enrichment of RNA polymeraseII and histone H3 trimethylation at lysine4 (H3K4me3) and H3K27me3 using chromatin immunoprecipitation, followed by sequencing analysis. The loci that were transcriptionally upregulated by a single bout of running exercise were marked by both H3K27me3 and H3K4me3, which were also correlated with the distribution of RNA polymeraseII. The genes that were not responsive to exercise exhibited high H3K4me3 occupancy, similar to the upregulated genes but with less H3K27me3. Next, we tested the effects of GSK343, a specific inhibitor of enhancer of zeste homologue2 (EZH2). Unexpectedly, GSK343 administration enhanced the H3K27me3 occupancy at the target loci, leading to the upregulation of gene responses to acute exercise. Administration of GSK343 also facilitated the phenotypic transformation of typeIIb to typeIIa fibres and the upregulation of AMPK phosphorylation and levels of heat shock protein70, pyruvate dehydrogenase kinase4, peroxisome proliferator-activated receptorγ coactivator-1α and muscle RING finger1. Furthermore, in contrast to the accelerated adaptation to exercise by GSK343, administration of the EZH1/2 dual inhibitor valemetostat prevented the changes in the aforementioned parameters after exercise training. These results indicate that exercise-induced H3K27me3 plays a key role in inducing exercise-related effects in the skeletal muscle. KEY POINTS: Exercise mediates histone H3 trimethylation at lysine 27 (H3K27me3) at transcriptionally upregulated loci in skeletal muscle, but the role of H3K27me3 in the adaptation of skeletal muscle to exercise training is unclear. Chromatin immunoprecipitation followed by sequencing analysis demonstrated that H3K27me3, in addition to H3K4me3 modifications, is the hallmark of sites showing higher responses to acute exercise. GSK343, a selective inhibitor of the enhancer of zeste homologue2 (EZH2), enhanced the gene responses to a single bout of exercise and accelerated the adaptive changes during exercise training in association with myonuclear H3K27me3 accumulation. Administration of valemetostat, an EZH1/2 dual inhibitor, repressed myonuclear H3K27me3 accumulation during training and caused a failure of adaptive changes. Exercise-induced H3K27me3 might play a key role in inducing exercise-related effects in skeletal muscle.

Fenofibrate Improves Cognitive Impairment Induced by High-Fat High-Fructose Diet: A Possible Role of Irisin and Heat Shock Proteins.

A high-fat, high-fructose diet (HFFD) impairs cognitive functions and increases susceptibility to neurodegenerative disorders. Irisin and heat shock protein 70 (HSP70) are well known for their role in neuroprotection. The possible neuroprotective effects of fenofibrate on HFFD-induced cognitive dysfunction and the involvement of irisin and HSP70 in these effects were investigated in this study. Rats were divided into normal control, HFFD, dimethylsulfoxide+HFFD, and fenofibrate+HFFD groups. At the end of the experiment, fenofibrate treatment restored hippocampus histological characteristics to almost normal and improved HFFD-induced cognitive deficit. It reduced body weight gain and had hypolipidemic effects by significantly lowering total cholesterol, triglycerides, and low-density lipoprotein cholesterol levels while increasing high-density lipoprotein cholesterol levels. It has antioxidant and anti-inflammatory effects as it significantly reduced the hippocampal malondialdehyde, interleukin-6, and tumor necrosis factor-alpha levels, while significantly increasing the reduced glutathione level. It prevented HFFD-induced hypoxia by significantly lowering hippocampal vascular endothelial growth factor and hypoxia-inducible factor-1 alpha levels. It significantly activated the hippocampal peroxisome proliferator-activated receptor-gamma coactivator-1 alpha (PGC-1α)/irisin/brain-derived neurotrophic factor pathway. It significantly increased hippocampal HSP70 while decreasing the HSP90 levels. It enhanced synaptic plasticity by significantly upregulating the hippocampal relative GluR1 gene expression. Furthermore, hippocampal irisin levels in the HFFD group were found to be positively correlated with cognitive function, hippocampal HSP70, and relative GluR1 gene expression levels, while negatively correlated with hippocampal HSP90 and HIF1α levels. Therefore, fenofibrate may be used as a potential medication to treat HFFD-induced neurodegenerative disorders.

Identification of Distinct Inflammatory Programs and Biomarkers in Systemic Juvenile Idiopathic Arthritis and Related Lung Disease by Serum Proteome Analysis.

Recent observations in systemic juvenile idiopathic arthritis (JIA) suggest an increasing incidence of high-mortality interstitial lung disease often characterized by a variant of pulmonary alveolar proteinosis (PAP). Co-occurrence of macrophage activation syndrome (MAS) and PAP in systemic JIA suggests a shared pathology, but patients with lung disease associated with systemic JIA (designated SJIA-LD) also commonly experience features of drug reaction such as atypical rashes and eosinophilia. This study was undertaken to investigate immunopathology and identify biomarkers in systemic JIA, MAS, and SJIA-LD. We used SOMAscan to measure ~1,300 analytes in sera from healthy controls and patients with systemic JIA, MAS, SJIA-LD, or other related diseases. We verified selected findings by enzyme-linked immunosorbent assay and lung immunostaining. Because the proteome of a sample may reflect multiple states (systemic JIA, MAS, or SJIA-LD), we used regression modeling to identify subsets of altered proteins associated with each state. We tested key findings in a validation cohort. Proteome alterations in active systemic JIA and MAS overlapped substantially, including known systemic JIA biomarkers such as serum amyloid A and S100A9, and novel elevations in the levels of heat-shock proteins and glycolytic enzymes. Interleukin-18 levels were elevated in all systemic JIA groups, particularly MAS and SJIA-LD. We also identified an MAS-independent SJIA-LD signature notable for elevated levels of intercellular adhesion molecule 5 (ICAM-5), matrix metalloproteinase 7 (MMP-7), and allergic/eosinophilic chemokines, which have been previously associated with lung damage. Immunohistochemistry localized ICAM-5 and MMP-7 in the lungs of patients with SJIA-LD. The ability of ICAM-5 to distinguish SJIA-LD from systemic JIA/MAS was independently validated. Serum proteins support a systemic JIA-to-MAS continuum; help distinguish systemic JIA, systemic JIA/MAS, and SJIA-LD; and suggest etiologic hypotheses. Select biomarkers, such as ICAM-5, could aid in early detection and management of SJIA-LD.