Stress-associated Proteins Research Articles

Involvement of endoplasmic reticulum stress in amyloid β (1-42)-induced Alzheimer’s like neuropathological process in rat brain

Amyloid-β (Aβ) accumulation in the brain is a pathological hallmark of Alzheimer’s disease (AD). Endoplasmic reticulum (ER) stress has been implicated in aetiology of neurodegenerative disorders. We studied the involvement of ER stress in Aβ-induced neuronal degeneration in rat brain to correlate it with cellular and molecular modifications in Aβ-induced Alzheimer’s like neuropathological process. Aβ (1-42) (5 μg) was administered by bilateral intracerebroventricular (icv) injection in the brain of adult male Wistar rats. Acetylcholinesterase (AChE) activity and histological alterations were observed in different brain regions. ER stress-associated proteins- glucose regulated protein-78 (GRP78), eukaryotic translation initiation factor-2α (eIF2α) and growth arrest and DNA damage-inducible protein-153 (GADD153), neuronal marker- microtubule associated protein-2 (MAP-2) and microglial protein- ionized calcium binding adaptor molecule-1 (Iba-1) were measured by western blot. Reduced glutathione (GSH), nitrite level and levels of caspase-12 and caspase-3 were also measured. ER stress inhibitor, salubrinal (1 mg/kg, intraperitoneally, ip) was used to assess the specific role of ER stress. Aβ (1-42)-induced increase in AChE activity, GRP78 and GADD protein levels, dephosphorylation of eIF2-α and caspase-12 and caspase-3 levels and decrease in GSH and MAP-2 levels were attenuated by salubrinal. Increase in Iba-1 protein and nitrite levels after Aβ (1-42) administration were partially attenuated by salubrinal. Aβ (1-42)-induced histological alterations were correlated with findings of ER stress. Results of present study implicate ER stress as a potential molecular mechanism in Aβ-induced Alzheimer’s like neuropathology which could serve as surrogate biomarker for study of AD progression and efficacy of therapeutic interventions for AD management.

Leech extract: A candidate cardioprotective against hypertension-induced cardiac hypertrophy and fibrosis

The prevalence of cardiovascular diseases (CVDs) has been increasing worldwide. Despite significant improvements in therapeutics and on-going developments of novel targeted-treatment regimens, cardiac diseases lack effective preventive and curative therapies with minimal side effects. Therefore, there is an urgent need to identify and propagate alternative and complementary therapies against cardiovascular diseases. Some traditional Chinese medicines can contribute to the prevention and treatment of CVDs and other chronic diseases, with few side effects. Hirudo, a medicinal leech, has been acclaimed for improving blood circulation and overcoming blood stagnation; however, the precise molecular mechanisms of leech extract treatment against pathological cardiac remodeling remain elusive. In this study, we aimed to delineate the molecular mechanisms of medicinal leech extract in the treatment of cardiac hypertrophy and fibrosis, using both in vitro and in vivo assessments. We conducted in vitro and in vivo animal experiments, including cell-viability assays, fluorescence microscopy, immunoblotting, immunohistochemistry, and Masson's trichrome staining. Pre-treatment with leech extract conferred a survival benefit to spontaneously-hypertensive rats (SHRs) and significantly reduced angiotensin II (ANG II)-induced cardiac hypertrophy and fibrosis. ANG II-stimulated cardiac hypertrophy markers were attenuated by leech extract treatment, versus controls. Translational expression of stress-associated mitogen-activated protein kinases (MAPKs) was also repressed. In vivo, leech extract treatment significantly ameliorated the cardiac hypertrophy phenotype in SHRs and diminished interstitial fibrosis, accompanied with reduced fibrosis markers. Leech extract treatment under a hypertensive condition exerted significant cardio-protective benefits by reducing the expression of cardiac hypertrophy-related transcription factors, stress-associated MAPKs, and fibrosis mediators. Our findings imply that medicinal leach extract may be effective against hypertension-induced cardiac hypertrophy and fibrosis.

Rice lectin protein r40c1 imparts drought tolerance by modulating S-adenosylmethionine synthase 2, stress-associated protein 8 and chromatin-associated proteins.

Lectin proteins play an important role in biotic and abiotic stress responses in plants. Although the rice lectin protein Osr40c1 has been reported to be regulated by drought stress, the mechanism of its drought tolerance activity has not been studied so far. In this study, it is shown that expression of the Osr40c1 gene correlates with the drought tolerance potential of various rice cultivars. Transgenic rice plants overexpressing Osr40c1 were significantly more tolerant to drought stress than the wild-type plants. Furthermore, ectopic expression of the Osr40c1 gene in tobacco yielded a similar result. Interestingly, the protein displayed a nucleo-cytoplasmic localization and was found to interact with a number of drought-responsive proteins such as S-adenosylmethionine synthase 2 (OsSAM2), stress-associated protein 8 (OsSAP8), DNA-binding protein MNB1B (OsMNB1B), and histone 4 (OsH4). Silencing of each of these protein partners led to drought sensitivity in otherwise tolerant Osr40c1-expressing transgenic tobacco lines indicating that these partners were crucial for the Osr40c1-mediated drought tolerance in planta. Moreover, the association of Osr40c1 with these partners occurred specifically under drought stress forming a multi-protein complex. Together, our findings delineate a novel role of Osr40c1 in imparting drought tolerance by regulating OsMNB1B, OsSAM2, and OsH4 proteins, which presumably enables OsSAP8 to induce downstream gene expression.

Genomic characterization and expression profiles of stress-associated proteins (SAPs) in castor bean (Ricinus communis)

Stress-associated proteins (SAPs) are known as response factors to multiple abiotic and biotic stresses in plants. However, the potential physiological and molecular functions of SAPs remain largely unclear. Castor bean (Ricinus communis L.) is one of the most economically valuable non-edible woody oilseed crops, able to be widely cultivated in marginal lands worldwide because of its broad adaptive capacity to soil and climate conditions. Whether SAPs in castor bean plays a key role in adapting diverse soil conditions and stresses remains unknown. In this study, we used the castor bean genome to identify and characterize nine castor bean SAP genes (RcSAP). Structural analysis showed that castor bean SAP gene structures and functional domain types vary greatly, differing in intron number, protein sequence, and functional domain type. Notably, the AN1-C2H2–C2H2 zinc finger domain within RcSAP9 has not been often observed in other plant families. High throughput RNA-seq data showed that castor bean SAP gene profiles varied among different tissues. In addition, castor bean SAP gene expression varied in response to different stresses, including salt, drought, heat, cold and ABA and MeJA, suggesting that the transcriptional regulation of castor bean SAP genes might operate independently of each other, and at least partially independent from ABA and MeJA signal pathways. Cis-element analyses for each castor bean SAP gene showed that no common cis-elements are shared across the nine castor bean SAP genes. Castor bean SAPs were localized to different regions of cells, including the cytoplasm, nucleus, and cytomembrane. This study provides a comprehensive profile of castor bean SAP genes that advances our understanding of their potential physiological and molecular functions in regulating growth and development and their responses to different abiotic stresses.

Identification of a Major QTL and Candidate Gene Analysis of Salt Tolerance at the Bud Burst Stage in Rice (Oryza sativa L.) Using QTL-Seq and RNA-Seq

BackgroundSalt stress is one of the main abiotic stresses that limits rice production worldwide. Rice salt tolerance at the bud burst stage directly affects the seedling survival rate and the final yield in the direct seeding cultivation model. However, the reports on quantitative trait locus (QTL) mapping and map-based cloning for salt tolerance at the bud burst stage are limited.ResultsHere, an F2:3 population derived from a cross between IR36 (salt-sensitive) and Weiguo (salt-tolerant) was used to identify salt-tolerant QTL interval at the bud burst stage using a whole-genome sequencing-based QTL-seq containing 40 extreme salt-tolerant and 40 extreme salt-sensitive individuals. A major QTL, qRSL7, related to relative shoot length (RSL) was detected on chromosome 7 using ΔSNP index algorithms and Euclidean Distance (ED) algorithms. According to single nucleotide polymorphisms (SNPs) between the parents, 25 Kompetitive allele-specific PCR (KASP) markers were developed near qRSL7, and regional QTL mapping was performed using 199 individuals from the F2:3 population. We then confirmed and narrowed down qRSL7 to a 222 kb genome interval. Additionally, RNA sequencing (RNA-seq) was performed for IR36 and Weiguo at 36 h after salt stress and control condition at the bud burst stage, and 5 differentially expressed genes (DEGs) were detected in the candidate region. The qRT-PCR results showed the same expression patterns as the RNA-seq data. Furthermore, sequence analysis revealed a 1 bp Indel difference in Os07g0569700 (OsSAP16) between IR36 and Weiguo. OsSAP16 encodes a stress-associated protein whose expression is increased under drought stress.ConclusionThese results indicate that OsSAP16 was the candidate gene of qRSL7. The results is useful for gene cloning of qRSL7 and for improving the salt tolerance of rice varieties by marker assisted selection (MAS).

MAPK Enzymes: a ROS Activated Signaling Sensors Involved in Modulating Heat Stress Response, Tolerance and Grain Stability of Wheat under Heat Stress.

Mitogen-activated protein kinase (MAPK) signaling cascade is highly conserved across the species triggering the self-adjustment of the cells by transmitting the external signals to the nucleus. The cascade consists of MAPK kinase kinases (MAPKKKs), MAPK kinases (MAPKKs) and MAPKs. These kinases are functionally interrelated through activation by sequential phosphorylation. MAPK cascade is involved in modulating the tolerance and regulating the growth and developmental processes in plants through transcriptional programming. The cascade has been well characterized in Arabidopsis, Tobacco and rice, but limited information is available in wheat due to complexity of genome. MAPK-based sensors have been reported to be highly specific for the external or intracellular stimuli activating specific TF, stress-associated genes (SAGs) and stress-associated proteins (SAPs) linked with heat-stress tolerance and other biological functions especially size, number and quality of grains. Even, MAPKs have been reported to influence the activity of ATP-binding cassette (ABC) transporter superfamily involved in stabilizing the quality of the grains under adverse conditions. Wheat has also diverse network of MAPKs involved in transcriptional reprogramming upon sensing the terminal HS and in turn protect the plants. Current review mainly focuses on the role of MAPKs as signaling sensor and modulator of defense mechanism for mitigating the effect of heat on plants with focus on wheat. It also indirectly protects the nutrient depletion from the grains under heat stress. MAPKs, lying at pivotal positions, can be utilized for manipulating the heat-stress response (HSR) of wheat to develop plant for future (P4F).

Differential impact of some metal(loid)s on oxidative stress, antioxidant system, sulfur compounds, and protein profile of Indian mustard (Brassica juncea L.).

Levels of arsenic (As), chromium (Cr), and copper (Cu) are increasing in the soils worldwide. Such contaminants cause toxicity in the plant systems which adversely affects growth and productivity. The objective of the present investigation was to elucidate individual and combined effects of As, Cr, and Cu (100μM each) stress in metal hyper-accumulator plant Indian mustard (Brassica juncea L.), exposed for a week. The highest accumulation was in the roots and in decreasing order viz. Cu > As > Cr. The magnitude of oxidative stress was maximal in combined stress, followed by As, Cr, and then Cu stress. Glutathione in conjunction with glutathione reductase, glutathione peroxidase, and glutathione S-transferase increased in all set of stress treatments, notably when exposed to Cr alone. In addition, the level of sulfur-rich compounds like cysteine, phytochelatins, and non-protein thiols increased under each stress indicating efficient coupling of the enzyme system and sulfur-containing compounds during stress conditions. The highest tolerance or growth index of plants was recorded for Cu. Protein profiling of leaf tissues showed modulation of protein patterns in each stress. Mediator of RNA polymerase II transcription subunit 1 isoform X1, RuBisCO (large subunit), and ribosomal protein S3 proteins were more abundant under Cr and Cu stress. Zinc finger A20/AN1 domain-containing stress-associated protein 5-like protein was more abundant under Cu stress. HSP (15.7kDa) and autophagy protein 5-like were in higher abundance under As and combined stress. Our results suggest that Indian mustard has a differential mode of defense against a particular stressor at the level of protein expression profile.

Characterization of a novel LmSAP gene promoter from Lobularia maritima: Tissue specificity and environmental stress responsiveness.

Halophyte Lobularia maritima LmSAP encodes an A20AN1 zinc-finger stress-associated protein which expression is up-regulated by abiotic stresses and heavy metals in transgenic tobacco. To deepen our understanding of LmSAP function, we isolated a 1,147 bp genomic fragment upstream of LmSAP coding sequence designated as PrLmSAP. In silico analyses of PrLmSAP revealed the presence of consensus CAAT and TATA boxes and cis-regulatory elements required for abiotic stress, phytohormones, pathogen, and wound responses, and also for tissue-specific expression. The PrLmSAP sequence was fused to the β-glucuronidase (gusA) reporter gene and transferred to rice. Histochemical GUS staining showed a pattern of tissue-specific expression in transgenic rice, with staining observed in roots, coleoptiles, leaves, stems and floral organs but not in seeds or in the root elongation zone. Wounding strongly stimulated GUS accumulation in leaves and stems. Interestingly, we observed a high stimulation of the promoter activity when rice seedlings were exposed to NaCl, PEG, ABA, MeJA, GA, cold, and heavy metals (Al3+, Cd2+, Cu2+ and Zn2+). These results suggest that the LmSAP promoter can be a convenient tool for stress-inducible gene expression and is a potential candidate for crop genetic engineering.

The root-knot nematode effector MiPDI1 targets a stress-associated protein (SAP) to establish disease in Solanaceae and Arabidopsis.

Large amounts of effectors are secreted by the oesophageal glands of plant-parasitic nematodes, but their molecular mode of action remains largely unknown. We characterized a Meloidogyne incognita protein disulphide isomerase (PDI)-like effector protein (MiPDI1) that facilitates nematode parasitism. In situ hybridization showed that MiPDI1 was expressed specifically in the subventral glands of M.incognita. It was significantly upregulated during parasitic stages. Immunolocalization demonstrated MiPDI1 secretion in planta during nematode migration and within the feeding cells. Host-induced silencing of the MiPDI1 gene affected the ability of the nematode to infect the host, whereas MiPDI1 expression in Arabidopsis increased susceptibility to M.incognita, providing evidence for a key role of MiPDI1 in M.incognita parasitism. Yeast two-hybrid, bimolecular fluorescence complementation and coimmunoprecipitation assays showed that MiPDI1 interacted with a tomato stress-associated protein (SlSAP12) orthologous to the redox-regulated AtSAP12, which plays an important role in plant responses to abiotic and biotic stresses. SAP12 silencing or knocking out in Nicotiana benthamiana and Arabidopsis increased susceptibility to M.incognita. Our results suggest that MiPDI1 acts as a pathogenicity factor promoting disease by fine-tuning SAP-mediated responses at the interface of redox signalling, defence and stress acclimation in Solanaceae and Arabidopsis.

Pristimerin Exacerbates Cellular Injury in Conditionally Reprogrammed Patient-Derived Lung Adenocarcinoma Cells by Aggravating Mitochondrial Impairment and Endoplasmic Reticulum Stress through EphB4/CDC42/N-WASP Signaling.

Lung cancer is the most common and lethal malignant disease for which the development of efficacious chemotherapeutic agents remains an urgent need. Pristimerin (PRIS), a natural bioactive component isolated from various plant species in the Celastraceae and Hippocrateaceae families, has been reported to exhibit outstanding antitumor effects in several types of cells. However, the underlying mechanisms involved remain poorly understood. Here, we reported the novel finding that PRIS significantly suppressed lung cancer growth in conditionally reprogrammed patient-derived lung adenocarcinoma cells (CRLCs). We demonstrated that PRIS inhibited the cell viabilities, migrative and invaded abilities, and capillary structure formation of CRLCs. Furthermore, our results clarified that PRIS induced mitochondrial dysfunction through reactive oxygen species (ROS) generation, activation of caspase-9, caspase-3, and caspase-4, and expression of endoplasmic reticulum (ER) stress-associated proteins. Inhibition of ER stress by 4-PBA (4-phenylbutyric acid, a specific ER stress inhibitor) or CHOP siRNA transfection ameliorated PRIS-induced loss of mitochondrial membrane potential and intrinsic apoptosis. The present study also provides mechanistic evidence that PRIS suppressed the EphB4/CDC42/N-WASP signaling pathway, which is required for mitochondrial-mediated intrinsic apoptosis, activation of ER stress, and stimulation of caspase-4 induced by PRIS, and consequently resulting in suppressed cell viability, migration, and angiogenesis in CRLCs. Taken together, by providing a mechanistic insight into the modulation of ER stress-induced cell death in CRLCs by PRIS, we suggest that PRIS has a strong potential of being a new antitumor therapeutic agent with applications in the fields of human lung adenocarcinoma.

Let-7b-5p is involved in the response of endoplasmic reticulum stress in acute pulmonary embolism through upregulating the expression of stress-associated endoplasmic reticulum protein 1.

The endogenous non-coding microRNA (miRNA) let-7b-5p is highly expressed in the blood of patients with acute pulmonary embolism (PE). However, the mechanism underlying the involvement of let-7b-5p in acute PE remains unclear. To address this, we investigated the role of let-7b-5p in acute PE in both in vitro and in vivo experimental models. The results showed that let-7b-5p upregulated the expression of stress-associated endoplasmic reticulum protein 1 (SERP1) at the post-transcriptional level. SERP1 activation leads to modulation of its chaperone protein SEC61B in the response of endoplasmic reticulum (ER) stress. Furthermore, our data show that the unfolded protein response was triggered and activation of unfolded proteins GRP78, PERK, RNF121, and CHOP occurred through the PERK-CHOP pathway, resulting in an inflammatory response and apoptosis of lung epithelial cells. These characteristics were promoted by the in vitro expression of a let-7b-5p mimic; conversely, transfection with a let-7b-5p inhibitor decreased the response of ER stress in acute PE. The results from this study thus provide evidence that let-7b-5p promotes protein processing during ER stress response by upregulating SERP1 expression, ultimately resulting in an inflammatory response and apoptosis of lung cells, cumulatively playing a critical role in the pathogenesis of acute PE.

Targeting NUPR1 with the small compound ZZW-115 is an efficient strategy to treat hepatocellular carcinoma

HCC is a highly lethal malignancy with Sorafenib as the only molecularly targeted drug. The multifunctional stress-associated protein, NUPR1, plays an essential role in controlling cell growth, migration, invasion and Sorafenib resistance in HCC. We report here that NUPR1 expression is absent in healthy liver and it is progressively upregulated in HCC premalignant lesions such as hepatitis and cirrhosis with a maximum expression in HCC samples, highlighting that NUPR1 is a potential drug target for HCC. We therefore assessed in this work, ZZW-115, a strong inhibitor of NUPR1, as a promising candidate for the treatment of HCC. We validated its extraordinary antitumor effect on HCC by using two HCC cell lines, HepG2-and Hep3B, both in cell based experiments and xenografted mice. We further revealed that ZZW-115 treatment induced cell death by apoptosis and necroptosis mechanisms, with a concomitant mitochondrial metabolism failure that triggers lower ATP production. Furthermore, the ATP depletion cannot be rescued by the apoptosis inhibitor Z-VAD-FMK and/or the necrosis inhibitor Necrostatin-1, indicating that ZZW-115 induces cell death through the mitochondrial failure.

Di-2-picolylamine triggers caspase-independent apoptosis by inducing oxidative stress in human liver hepatocellular carcinoma cells.

Di-2-picolylamine (DPA) is an organic compound that has been shown to possess antioxidant properties when conjugated to form a metal complex. The basis of this study was to determine the effects of DPA on the proliferation and apoptosis of human hepatocellular carcinoma cells and elucidate the possible mechanisms. The methylthiazol tetrazolium assay served to measure cell viability and generated an IC50 of 1591 µM. Luminometry was used to investigate caspase activity and ATP concentration. It was observed that the decreased cell viability was associated with reduced ATP levels. Despite increased Bax and caspase 9 activity, cell death was caspase independent as indicated by the reduction in caspase 3/7 activity. This was associated with the downregulation poly(ADP-ribose) polymerase cleavage (Western blotting). However, the Hoescht assay depicted nuclear condensation and apoptotic body formation with elevated DPA levels suggesting DNA damage in HepG2 cells. DNA damage assessed by the comet assay confirmed an increased comet tail formation. The presence of oxidative stress was investigated by quantifying reactive species (malondialdehyde and nitrates concentration) and Western blotting to confirm the expression of antioxidant proteins. The DPA increased lipid peroxidation (RNS), a marker of oxidative stress, consequently causing cell death. The accompanying upregulation of stress-associated proteins superoxide dismutase (SOD2), nuclear factor (erythroid-derived 2)-like 2 (Nrf2), and Hsp70 verifies oxidative stress.

A Lobularia maritima LmSAP protein modulates gibberellic acid homeostasis via its A20 domain under abiotic stress conditions.

Stress-associated proteins (SAPs) are favorable targets to improve stress tolerance in plants, owing to their roles in developmental processes and stress responses. However, the role of SAPs and the molecular mechanisms by which they regulate plant stress responses remain poorly understood. Previously, it was reported that LmSAP expression was upregulated by various abiotic stressors in Lobularia maritima, and that transgenic tobacco lines with constitutively expressed LmSAPΔA20 and LmSAPΔA20-ΔAN1 showed dwarf phenotypes due to the deficiency of cell elongation under salt and osmotic stresses. In this study, we examined the function of A20 domain in the GA pathway in response to abiotic stresses. Transient expression of acGFP-LmSAPΔA20 and acGFP-LmSAPΔA20-ΔAN1 in onion epidermal cells demonstrated that these fused proteins were localized in the nucleo–cytoplasm. However, the truncated form acGFP-LmSAPΔAN1 was localized in the nucleus. Moreover, comparison of native and truncated LmSAP showed dramatic structural changes caused by the deletion of the A20 domain, leading to loss of function and localization. Interestingly, overexpression LmSAP and truncated LmSAPΔAN1 led to up-regulation of GA biosynthetic genes and increased total gibberellins (GAs) content, corresponding with accelerated development in transgenic tobacco plants. Moreover, the dwarf phenotype of the transgenic lines that express LmSAPΔA20 and LmSAPΔA20-ΔAN1 under stress conditions was fully restored by the application of exogenous GA3. These findings improve our understanding of the role of LmSAP in regulating GA homeostasis, which is important for regulating plant development under abiotic stress conditions.

Pharmacological inhibition of PRMT7 links arginine monomethylation to the cellular stress response

Protein arginine methyltransferases (PRMTs) regulate diverse biological processes and are increasingly being recognized for their potential as drug targets. Here we report the discovery of a potent, selective, and cell-active chemical probe for PRMT7. SGC3027 is a cell permeable prodrug, which in cells is converted to SGC8158, a potent, SAM-competitive PRMT7 inhibitor. Inhibition or knockout of cellular PRMT7 results in drastically reduced levels of arginine monomethylated HSP70 family stress-associated proteins. Structural and biochemical analyses reveal that PRMT7-driven in vitro methylation of HSP70 at R469 requires an ATP-bound, open conformation of HSP70. In cells, SGC3027 inhibits methylation of both constitutive and inducible forms of HSP70, and leads to decreased tolerance for perturbations of proteostasis including heat shock and proteasome inhibitors. These results demonstrate a role for PRMT7 and arginine methylation in stress response.

Heavy Metal Stress-Associated Proteins in Rice and Arabidopsis: Genome-Wide Identification, Phylogenetics, Duplication, and Expression Profiles Analysis.

Heavy metal exposure is a serious environmental stress in plants. However, plants have evolved several strategies to improve their heavy metal tolerance. Heavy metal-associated proteins (HMPs) participate in heavy metal detoxification. Here, we identified 46 and 55 HMPs in rice and Arabidopsis, respectively, and named them OsHMP 1–46 and AtHMP 1–55 according to their chromosomal locations. The HMPs from both plants were divided into six clades based on the characteristics of their heavy metal-associated domains (HMA). The HMP gene structures and motifs varied greatly among the different classifications. The HMPs had high collinearity and were segmentally duplicated. A cis-element analysis revealed that the HMPs may be regulated by different transcription factors. An expression profile analysis disclosed that only eight OsHMPs were constitutive in rice tissues. Of these, the expression of OsHMP37 was far higher than that of the other seven genes while OsHMP28 was expressed exclusively in the roots. For Arabidopsis, nine AtHMPs presented with very high transcript levels in all organs. Most of the selected OsHMPs were differentially expressed in various tissues under different heavy metal stresses. Only OsHMP09, OsHMP18, and OsHMP22 showed higher expression levels in all tissues under different heavy metal stresses. In contrast, most of the selected AtHMPs had nearly constant expression levels in different tissues under various heavy metal stresses. The AtHMP20, AtHMP23, AtHMP25, AtHMP31, AtHMP35, AtHMP46 expression levels under different heavy metal stresses were higher in the leaves and roots. The foregoing discoveries elucidated HMP evolution in monocotyledonous and dicotyledonous plants and may helpful functionally characterize HMPs in the future.

Bee bread attenuates high fat diet induced renal pathology in obese rats via modulation of oxidative stress, downregulation of NF-kB mediated inflammation and Bax signalling

Context: Global prevalence of obesity is increasing. Objective: To study the effect of bee bread (BB) on serum renal function parameters, oxidative stress, inflammatory and B-cell associated protein X (Bax) in the kidneys of high fat diet (HFD) obese rats. Methods: Thirty-six male Sprague Dawley rats were used. Control: received rat diet and water (1 mL/kg); HFD group: received HFD and water (1 mL/kg): bee bread (BB) preventive or orlistat preventive: received HFD and BB (0.5 g/kg) or HFD and orlistat (10 mg/kg); BB or orlistat treatment: received BB (0.5 g/kg) or orlistat (10 mg/kg). Results: HFD group had increased body weight, Body Mass Index, Lee Obesity Indices, kidney weights, malondialdehyde, inflammatory markers, Bax; decreased glutathione peroxidase, glutathione-S-transferase, superoxide dismutase, total antioxidant activity, no differences (p > .05) in food intakes, serum creatinine, sodium, potassium, chloride, catalase compared to control. Conclusion: BB modulated most of these parameters, as corroborated by histology.

Global transcriptome analysis of novel stress associated protein (SAP) genes expression dynamism of combined abiotic stresses in Oryza sativa (L.)

Genes encoding proteins with A20/AN1 zinc-finger domains, belonging to the stress associated protein (SAP) gene family, are present in all eukaryotes and play a decisive role in plant response to diverse physiological and molecular activities particularly on biotic and abiotic stresses (AbS). In this first and foremost study, global transcriptome analysis of members of the SAP gene family was carried out in C3 model-Oryza sativa (OsSAP) aiming at the identification of OsSAP genes activated in response to unique or Combined AbS (CAbS). Based on the available spatio-temporal and phytohormonal RNA-Seq expression profile datasets, nine OsSAP genes were filtered out and identified by a differential expression signature noted in various tissues as well as plant hormones. Comparative genome ideogram of OsSAP genes confirmed the orthologous collinearity with C4 panicoid genomes. Interactome of these genes, revealed the molecular cross-talks of OsSAP. Thus, the computational expression signature of OsSAP genes led to a better understanding of gene dynamism in diverse developmental tissues/organs. Transcriptional regulation analysis of key OsSAP genes in response to stress (drought and salinity) suggested the novel role of OsSAP1, OsSAP2, OsSAP5, OsSAP7, OsSAP8 and OsSAP11 in AbS. Altogether, the study provides deeper insights on molecular characteristics of OsSAP genes, which could be deployed further to decipher their precise functional roles in AbS responses. Communicated by Ramaswamy H. Sarma

Bis(ethylmaltolato)oxidovanadium (IV) mitigates neuronal apoptosis resulted from amyloid-beta induced endoplasmic reticulum stress through activating peroxisome proliferator-activated receptor γ

Neuronal apoptosis caused by amyloid-beta (Aβ) overproduction is one of the most important pathological features in Alzheimer's disease (AD). Endoplasmic reticulum (ER) stress induced by Aβ overload plays a critical role in this process. Bis(ethylmaltolato)oxidovanadium (IV) (BEOV), a vanadium compound which had been regarded as peroxisome proliferator-activated receptor γ (PPARγ) agonist, was reported to exert an antagonistic effect on ER stress. In this study, we tested whether BEOV could ameliorate the Aβ-induced neuronal apoptosis by inhibiting ER stress. It was observed that BEOV treatment ameliorated both tunicamycin-induced and/or Aβ-induced ER stress and neurotoxicity in a dose-dependent manner through downgrading ER stress-associated and apoptosis-associated proteins in primary hippocampal neurons. Consistent with in vitro results, BEOV also reduced ER stress and inhibited neuronal apoptosis in hippocampi and cortexes of transgenic AD model mice. Moreover, by adopting GW9662 and salubrinal, the inhibitor of PPARγ and hyperphosphorylated eukaryotic translation initiation factor 2α, respectively, we further confirmed that BEOV alleviated Aβ–induced ER stress and neuronal apoptosis in primary hippocampal neurons by activating PPARγ. Taken together, these results provided scientific evidences to support the concept that BEOV ameliorates Aβ–induced ER stress and neuronal apoptosis through activating PPARγ.

Identification and Expression Analysis of Stress-Associated Proteins (SAPs) Containing A20/AN1 Zinc Finger in Cucumber.

Stress-associated proteins (SAPs) are a class of zinc finger proteins that confer tolerance to a variety of abiotic and biotic stresses in diverse plant species. However, in cucumber (Cucumis sativus L.), very little is known about the roles of SAP gene family members in regulating plant growth, development, and stress responses. In this study, a total of 12 SAP genes (named as CsSAP1-CsSAP12) were identified in the cucumber genome, which were unevenly distributed on six chromosomes. Gene duplication analysis detected one tandem duplication and two segmental duplication events. Phylogenetic analysis of SAP proteins from cucumber and other plants suggested that they could be divided into seven groups (sub-families), and proteins in the same group generally had the same arrangement of AN1 (ZnF-AN1) and A20 (ZnF-A20) domains. Most of the CsSAP genes were intronless and harbored a number of stress- and hormone-responsive cis-elements in their promoter regions. Tissue expression analysis showed that the CsSAP genes had a broad spectrum of expression in different tissues, and some of them displayed remarkable alteration in expression during fruit development. RT-qPCR results indicated that all the selected CsSAP genes displayed transcriptional responses to cold, drought, and salt stresses. These results enable the first comprehensive description of the SAP gene family in cucumber and lay a solid foundation for future research on the biological functions of CsSAP genes.