scholarly journals Roles of the Exogenous H2S-Mediated SR-A Signaling Pathway in Renal Ischemia/ Reperfusion Injury in Regulating Endoplasmic Reticulum Stress-Induced Autophagy in a Rat Model

2017 ◽  
Vol 41 (6) ◽  
pp. 2461-2474 ◽  
Author(s):  
Qing Ling ◽  
Xiao Yu ◽  
Tao Wang ◽  
Shao-Gang Wang ◽  
Zhang-Qun Ye ◽  
...  
Keyword(s):  
Protein Expression ◽  
Er Stress ◽  
Signaling Pathway ◽  
Cell Apoptosis ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Urine Volume ◽  
Urinary Protein ◽  
Apoptosis Index ◽  
Mrna And Protein Expression

Objective: This study aims to explore the effects of the exogenous hydrogen sulfide (H2S)-mediated scavenger receptor A (SR-A) signaling pathway on renal ischemia/reperfusion injury (IRI) by regulating endoplasmic reticulum (ER) stress-induced autophagy in rats. Methods: A total of 48 normal Sprague-Dawley (SD) rats and SR-A knockout rats were selected and divided into six groups (n = 8): wild-type (WT) + sham, WT + ischemia-reperfusion (I/R), WT + I/R + NaHS, SR-A-/- + sham, SR-A-/- + I/R and SR-A-/- + I/R + NaHS. The concentrations of urinary protein, blood urea nitrogen (BUN), serum creatinine (SCR), malondialdehyde (MDA) and H2S in renal tissue were detected. qRT-PCR and Western blotting were used to detect the mRNA and protein levels of IL-6, TGF-β, SR-A, LC3I, LC3II, P62, PERK, ATF6 and IRE1 pathway-related genes. A TUNEL assay was used to detect cell apoptosis. Electron microscopy was applied to observe the structure of renal autophagosomes. Results: Compared with the WT + sham group, in the rates of the WT + I/R group, the urine volume, urinary protein, BUN, SCR and MDA concentrations, the mRNA and protein expression of IL-6, TGF-β, LC3II/I, and ER stress pathway-related genes, the cell apoptosis index, and the number of autophagosomes were significantly increased 24 h after I/R, while P62 and SR-A protein expression and SOD and H2S concentrations were significantly decreased (all P < 0.05). The levels of renal injury, autophagy and ER stress pathway-related genes were decreased in the WT + I/R + NaHS group but were increased in the SR-A-/- + I/R group relative to the WT + I/R group. No significant differences were observed in the urine volume; the concentrations of urinary protein, BUN, SCR and MDA; the SOD activity; the mRNA and protein expression of IL-6, TGF-β, SR-A, GRP78, SR-A, GPR94, ATF4, IRE1, XBP1, ATF6, and eIF2α; the cell apoptosis index; or the number of autophagosomes in rats of the SR-A-/- + I/R and SR-A-/- + I/R + NaHS groups (all P > 0.05). Conclusion: These results demonstrate that the exogenous H2S-mediated SR-A signaling pathway reduces renal IRI injury by up-regulating ER stress-induced autophagy in rats.

scholarly journals Anthocyanin attenuates oxygen-glucose deprivation/reperfusion-induced apoptosis of PC12 cells via inactivation of ASK1/JNK/p38 signaling pathway

2021 ◽  
Vol 18 (10) ◽  
pp. 2037-2043
Author(s):  
Hong Zhu ◽  
Dan Ren ◽  
Lan Xiao ◽  
Ting Zhang ◽  
Ruomeng Li ◽  
...  
Keyword(s):  
Cell Viability ◽  
Signaling Pathway ◽  
Pc12 Cells ◽  
Cell Apoptosis ◽  
Cell Injury ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Glucose Deprivation ◽  
Oxygen Glucose Deprivation ◽  
Induced Apoptosis

Purpose: To investigate whether the cytoprotective effect of anthocyanin (Anc) on oxygen-glucose deprivation/reperfusion (OGD/R)-induced cell injury is related to apoptosis signal-regulating kinase 1 (ASK1)/c-Jun N-terminal kinase (JNK)/p38 signaling pathway. Methods: PC12 cells were pre-treated with various concentrations of Anc (10, 50, and 100 μg/mL) in OGD/R-induced cell injury model. The 3-(4, 5)-dimethylthiahiazo (-z-y1)-3, 5-di-phenytetrazoliumromide (MTT) assay was used to assess cell viability. Cell apoptosis was measured by lactic acid dehydrogenase (LDH) release assay and flow cytometry. Western blot was employed to determine the protein expressions of BCL-2, BAX, caspase-3, p-ASK1 (Thr845), p-JNK, and p-p38. Results: The results indicate that Anc increased the viability of PC12 cells after OGD/R exposure (p < 0.05), and also efficiently rescued OGD/R-induced apoptosis (p < 0.05). Mechanistic studies showed that these protective roles of Anc are related to the inhibition of ASK1/JNK/p38 signaling pathway. Conclusion: The results indicate Anc protects against OGD/R-induced cell injury by enhancing cell viability and inhibiting cell apoptosis. The underlying mechanism of action is partly via inactivation of ASK1/JNK/p38 signaling pathway. Thus, Anc has promise as a potential natural agent to prevent and treat cerebral ischemia-reperfusion injury.

scholarly journals Downregulating Serine Hydroxymethyltransferase 2 Deteriorates Hepatic Ischemia-Reperfusion Injury through ROS/JNK/P53 Signaling in Mice

2019 ◽  
Vol 2019 ◽  
pp. 1-9
Author(s):  
Hao Wu ◽  
He Bai ◽  
Shigang Duan ◽  
Fangchao Yuan
Keyword(s):  
Signaling Pathway ◽  
Cell Apoptosis ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Liver Weight ◽  
Serine Hydroxymethyltransferase ◽  
Hepatic Ischemia ◽  
P53 Signaling ◽  
Hepatic Ischemia Reperfusion ◽  
P53 Signaling Pathway

Background. Serine hydroxymethyltransferase 2 (SHMT2) activity ensures that cells have a survival advantage in ischemic conditions and regulates redox homeostasis. In this study, we aimed to investigate the role of SHMT2 after hepatic ischemia-reperfusion (IR), which involves hypoxia, ischemic conditions, and cell apoptosis. Methods. A 70% IR model was established in C57BL/6J mice with or without SHMT2 knockdown. H&E staining, liver weight/body weight, serum alanine aminotransferase (ALT), and aspartate aminotransferase (AST) levels and cell apoptosis were tested to analyze liver damage and function. Then, the related cellular signals were probed. Results. The level of SHMT2 protein was significantly increased at 24 h and 48 h after IR (p<0.001). Mice in the shSHMT2 group showed more necrotic areas and histological damage at 24 h (p<0.01) after IR and higher levels of serum ALT and AST (p<0.05) compared with those of mice in the scramble group. After IR for 24 h, the expression of TUNEL in the shSHMT2 group was significantly higher than that in the scramble group, as shown by histological analysis (p<0.01). Mechanistically, the JNK/P53 signaling pathway was activated by IR, and knockdown of SHMT2 exacerbated hepatocyte apoptosis. Conclusions. Knockdown of SHMT2 worsens IR injury through the ROS/JNK/P53 signaling pathway. Our discovery expands the understanding of both molecular and metabolic mechanisms involved in IR. SHMT2 is a possible therapeutic target to improve the prognosis of liver transplantation (LT) and subtotal hepatectomy.

scholarly journals Proanthocyanidins Antagonize Arsenic-Induced Oxidative Damage and Promote Arsenic Methylation through Activation of the Nrf2 Signaling Pathway

2019 ◽  
Vol 2019 ◽  
pp. 1-19 ◽  
Author(s):  
Mengchuan Xu ◽  
Qiang Niu ◽  
Yunhua Hu ◽  
Gangling Feng ◽  
Haixia Wang ◽  
...  
Keyword(s):  
Oxidative Damage ◽  
Protein Expression ◽  
Signaling Pathway ◽  
Cell Apoptosis ◽  
Oxidative Stress Marker ◽  
Average Growth ◽  
Methylation Index ◽  
Arsenic Methylation ◽  
Nrf2 Signaling Pathway ◽  
Mrna And Protein Expression

Purpose. To investigate the effects of grape seed proanthocyanidin extract (GSPE) on oxidative damage and arsenic (As) methylation and to clarify the role of Nrf2 in the process. Methods. L-02 cells were treated with arsenic (25 μM) and GSPE (10, 25, and 50 mg/L) for 24 h. Cell viability was analyzed by MTT assay. Cell apoptosis and ROS fluorescence were detected by flow cytometry. Oxidative stress marker levels were measured using commercial kits. mRNA and protein expression were detected by qRT-PCR and western blotting. The cellular concentrations of methylation products were measured by HPLC-HGAFS. Arsenic methylation ability of cells was determined. Results. Cell survival rate was significantly lower in the As group than in the control group (P<0.05), while cell apoptosis increased and the number of apoptotic cells decreased gradually after GSPE intervention. Superoxide dismutase, glutathione, and sulfhydryl levels in the intervention group were significantly higher (P<0.05), while MDA and ROS levels were significantly lower (P<0.05) than those in the As group. The mRNA and protein expression of Nrf2, HO-1, NQO1, and glutathione-S-transferase increased in the As + GSPE group compared with that in the As group (P<0.05). GSPE significantly increased methylated As level, primary methylation index, secondary methylation index, average growth rate of methylation, and average methylation speed compared with the GSPE untreated group (P<0.05). After Nrf2 inhibition, the effect of GSPE decreased significantly. Conclusion. GSPE activates the Nrf2 signaling pathway to antagonize As-induced oxidative damage and to promote As methylation metabolism. Therefore, GSPE may be a potential agent for relieving As-induced hepatotoxicity.

scholarly journals Luteolin Treatment Protects against Renal Ischemia-Reperfusion Injury in Rats

2017 ◽  
Vol 2017 ◽  
pp. 1-10 ◽  
Author(s):  
Xin Hong ◽  
Xiaojing Zhao ◽  
Gang Wang ◽  
Zhengliang Zhang ◽  
Honghong Pei ◽  
...  
Keyword(s):  
Er Stress ◽  
Cell Apoptosis ◽  
Renal Cell ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Neutrophil Infiltration ◽  
Renal Ischemia ◽  
Intragastric Administration ◽  
Sprague Dawley ◽  
Luteolin Treatment

Renal ischemia-reperfusion (I/R) injury is a common but severe scientific problem. Luteolin has great anti-inflammatory and antioxidant effects. In this study, we studied the effect of luteolin on renal I/R injury in rats. Intragastric administration of luteolin or saline was performed in Sprague-Dawley rats before (40 mg/kg for three days) and after (one day) renal I/R modeling. Kidney and blood samples were harvested to detect the severity of renal injury 24 hours after operation. The results showed that luteolin-treated rats exhibited milder histomorphological changes with lower scores of renal histological lesions; lower blood urea nitrogen and creatinine levels; lower renal malondialdehyde (MDA), 8-oxo-deoxyguanosine (8-OHdG), and myeloperoxidase (MPO) levels; and higher superoxide dismutase (SOD) and catalase (CAT) activities in the kidney. Luteolin attenuated the increased levels of serum and renal tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and IL-6, renal high mobility group box-1 (HMGB1), and nuclear factor kappaβ(NF-κB) expression levels in I/R rats. Furthermore, luteolin treatment significantly reduced renal cell apoptosis and endoplasmic reticulum (ER) stress caused by renal I/R injury. In conclusion, luteolin improved renal function in I/R rats by reducing oxidative stress, neutrophil infiltration, inflammation, renal cell apoptosis, and expression of HMGB1 and NF-κB, and ER stress.

scholarly journals Morphine post-conditioning-induced up-regulation of lncRNA TINCR protects cardiomyocytes from ischemia–reperfusion injury via inhibiting degradation and ubiquitination of FGF1

QJM ◽  
2020 ◽  
Vol 113 (12) ◽  
pp. 859-869
Author(s):  
M Wang ◽  
S Liu ◽  
H Wang ◽  
R Tang ◽  
Z Chen
Keyword(s):  
Cytochrome C ◽  
Cell Viability ◽  
Signaling Pathway ◽  
Cell Apoptosis ◽  
Mitochondrial Permeability Transition ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Cell Counting ◽  
Cytochrome C Release ◽  
Mptp Opening

Abstract Background Our previous study has demonstrated that morphine post-conditioning (MpostC) protects cardiomyocytes from ischemia/reperfusion (I/R) injury partly through activating protein kinase-epsilon (PKCε) signaling pathway and subsequently inhibiting mitochondrial permeability transition pore (mPTP) opening. Aim In this study, we aim to investigate the relationship between long non-coding RNA TINCR and PKCε in cardiomyocytes under MpostC-treated I/R injury. Design The myocardial I/R rat model was established by the ligation of lower anterior descending coronary artery for 45 min followed by the reperfusion for 1 h, and MpostC was performed before the reperfusion. Method H/R and MpostC were performed in the rat cardiomyocyte cell line (H9C2), and the Cytochrome-c release in cytosol and mPTP opening were determined. Cell viability was detected by using Cell Counting Kit-8, and cell apoptosis was determined by using flow cytometry or TUNEL assay. Results The results indicated that MpostC restored the expression of TINCR in I/R rat myocardial tissues. In cardiomyocytes, the therapeutic effect of MpostC, including reduced mPTP opening, reduced Cytochrome-c expression, increased cell viability and reduced cell apoptosis, was dramatically negated by interfering TINCR. The expression of fibroblast growth factor 1 (FGF1), a protein that activates PKCε signaling pathway, was positively correlated with TINCR. The RNA immunoprecipitation and RNA pull-down assay further confirmed the binding between FGF1 and TINCR. Furthermore, TINCR was demonstrated to inhibit the degradation and ubiquitination of FGF1 in cardiomyocytes using the cycloheximide experiment and the ubiquitination assay. The TINCR/FGF1/PKCε axis was revealed to mediate the protective effect of MpostC against hypoxia/reoxygenation injury both in vitro and in vivo. Conclusion In conclusion, our findings demonstrated that MpostC-induced up-regulation of TINCR protects cardiomyocytes from I/R injury via inhibiting degradation and ubiquitination of FGF1, and subsequently activating PKCε signaling pathway, which provides a novel insight in the mechanism of TINCR and PKCε during MpostC treatment of I/R injury.

scholarly journals Sestrin2 as a Potential Target for Regulating Metabolic-Related Diseases

2021 ◽  
Vol 12 ◽  
Author(s):  
Linan Gong ◽  
Zanzan Wang ◽  
Zhenggui Wang ◽  
Zhiguo Zhang
Keyword(s):  
Er Stress ◽  
Signaling Pathway ◽  
Metabolic Diseases ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Mammalian Target Of Rapamycin ◽  
Mtor Signaling ◽  
Mtor Signaling Pathway ◽  
Regulatory Relationship ◽  
Alcoholic Fatty Liver

Sestrin2 is a highly conserved protein that can be induced under a variety of stress conditions, including DNA damage, oxidative stress, endoplasmic reticulum (ER) stress, and metabolic stress. Numerous studies have shown that the AMP-activated protein kinase (AMPK)/mammalian target of rapamycin (mTOR) signaling pathway has a crucial role in the regulation of metabolism. Sestrin2 regulates metabolism via a number of pathways, including activation of AMPK, inhibition of the mTOR complex 1 (mTORC1), activation of mTOR complex 2 (mTORC2), inhibition of ER stress, and promotion of autophagy. Therefore, modulation of Sestrin2 activity may provide a potential therapeutic target for the prevention of metabolic diseases such as insulin resistance, diabetes, obesity, non-alcoholic fatty liver disease, and myocardial ischemia/reperfusion injury. In this review, we examined the regulatory relationship between Sestrin2 and the AMPK/mTOR signaling pathway and the effects of Sestrin2 on energy metabolism.

scholarly journals Sesamin Protects against and Ameliorates Rat Intestinal Ischemia/Reperfusion Injury with Involvement of Activating Nrf2/HO-1/NQO1 Signaling Pathway

2021 ◽  
Vol 2021 ◽  
pp. 1-15
Author(s):  
Yilin Wang ◽  
Jin Wen ◽  
Marwan Almoiliqy ◽  
Yaojia Wang ◽  
Zhihao Liu ◽  
...  
Keyword(s):  
Protein Expression ◽  
Signaling Pathway ◽  
Intestinal Ischemia ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Epithelial Cell Line ◽  
Tissue Cell ◽  
Nrf2 Signaling Pathway ◽  
Anti Inflammatory ◽  
Intestinal Ischemia Reperfusion

Intestinal ischemia-reperfusion (I/R) may induce cell/tissue injuries, leading to multiple organ failure. Based on our preexperiments, we proposed that sesamin could protect against and ameliorate intestinal I/R injuries and related disorders with involvement of activating Nrf2 signaling pathway. This proposal was evaluated using SD intestinal I/R injury rats in vivo and hypoxia/reoxygenation- (H/R-) injured rat small intestinal crypt epithelial cell line (IEC-6 cells) in vitro. Sesamin significantly alleviated I/R-induced intestinal histopathological injuries and significantly reduced serum biochemical indicators ALT and AST, alleviating I/R-induced intestinal injury in rats. Sesamin also significantly reversed I/R-increased TNF-α, IL-6, IL-1β, and MPO activity in serum and MDA in tissues and I/R-decreased GSH in tissues and SOD in both tissues and IEC-6 cells, indicating its anti-inflammatory and antioxidative stress effects. Further, sesamin significantly decreased TUNEL-positive cells, downregulated the increased Bax and caspase-3 protein expression, upregulated the decreased protein expression of Bcl-2 in I/R-injured intestinal tissues, and significantly reversed H/R-reduced IEC-6 cell viability as well as reduced the number of apoptotic cells among H/R-injured IEC-6 cell, showing antiapoptotic effects. Activation of Nrf2 is known to ameliorate tissue/cell injuries. Consistent with sesamin-induced ameliorations of both intestinal I/R injuries and H/R injuries, transfection of Nrf2 cDNA significantly upregulated the expression of Nrf2, HO-1, and NQO1, respectively. On the contrary, either Nrf2 inhibitor (ML385) or Nrf2 siRNA transfection significantly decreased the expression of these proteins. Our results suggest that activation of the Nrf2/HO-1/NQO1 signaling pathway is involved in sesamin-induced anti-inflammatory, antioxidative, and antiapoptotic effects in protection against and amelioration of intestinal I/R injuries.

scholarly journals Cardiomyocyte-derived adiponectin is biologically active in protecting against myocardial ischemia-reperfusion injury

2010 ◽  
Vol 298 (3) ◽  
pp. E663-E670 ◽  
Author(s):  
Yajing Wang ◽  
Wayne Bond Lau ◽  
Erhe Gao ◽  
Ling Tao ◽  
Yuexing Yuan ◽  
...  
Keyword(s):  
Protein Expression ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Biologically Active ◽  
Vehicle Group ◽  
Protective Effects ◽  
Nitrative Stress ◽  
Pharmacological Significance ◽  
Mrna And Protein Expression ◽  
Ldh Release

Adiponectin (APN) has traditionally been viewed as an adipocyte-specific endocrine molecule with cardioprotective effects. Recent studies suggest that APN is also expressed in cardiomyocytes. However, biological significances of this locally produced APN remain completely unknown. The aim of this study was to investigate the pathological and pharmacological significance of cardiac-derived APN in cardiomyocyte pathology. Adult cardiomyocytes from wild-type littermates (WT) or gene-deficient mice were pretreated with vehicle (V) or rosiglitazone (RSG) for 6 h followed by simulated ischemia-reperfusion (SI/R, 3 h/12 h). Compared with WT cardiomyocytes, myocytes from APN knockout (APN-KO) mice sustained greater SI/R injury, evidenced by greater oxidative/nitrative stress, caspase-3 activity, and lactate dehydrogenase (LDH) release ( P < 0.05). Myocytes from adiponectin receptor 1 knockdown (AdipoR1-KD) or AdipoR1-KD/AdipoR2-KO mice had slightly increased SI/R injury, but the difference was not statistically significant. RSG significantly ( P < 0.01) increased APN mRNA and protein expression, upregulated AdipoR1/AdipoR2 expression, reduced SI/R-induced apoptosis, and decreased LDH release in WT cardiomyocytes. However, the anti-oxidative/anti-nitrative and cell protective effects of RSG were completely lost in APN-KO cardiomyocytes ( P > 0.05 vs. vehicle group), although a comparable degree of AdipoR1/AdipoR2 upregulation was observed. The upregulatory effect of RSG on APN mRNA and protein expression was significantly potentiated in AdipoR1-KD/AdipoR2-KO cardiomyocytes. However, the cellular protective effects of RSG were significantly blunted, although not completely lost, in these cells. These results demonstrated that cardiomyocyte APN is biologically active in protecting cells against SI/R injury. Moreover, this locally produced APN achieves its protective effect primarily through paracrine/autocrine activation of APN receptors.

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