Preconditioning with endoplasmic reticulum stress alleviated heart ischemia/reperfusion injury via modulating IRE1/ATF6/RACK1/PERK and PGC-1α in diabetes mellitus

Yan, Bing; Liu, Suhuan; Li, Xuejun; Zhong, Yi; Tong, Fei; Yang, Shuyu

doi:10.1016/j.biopha.2019.109407

Cited by 27 publications

(18 citation statements)

References 31 publications

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“…Recent research has proposed that PPAR-γ agonists have a protective function when given in IRI, and the cardioprotective effects of PPAR-γ activation have been suggested to be due to an inhibition of the surge in oxidative molecules and inhibition of apoptosis as well as amelioration of inflammatory response. [23,24] The beneficial pharmacological effects of PPAR-γ ligands have been mainly attributed to their antiinflammatory property as past studies revealed that natural and synthetic PPAR-γ ligands have anti-inflammatory potentials. [2] One of the mechanisms by which PPAR-γ activation reduces inflammation is by decreasing the synthesis of NF-κB, which is a pivotal inflammatory transcription factor.…”

Section: Discussionmentioning

confidence: 99%

Cardioprotective effects of azilsartan compared with that of telmisartan on an in vivo model of myocardial ischemia‐reperfusion injury

Garg

Khan

Malhotra

et al. 2021

J Biochem & Molecular Tox

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Azilsartan is found to be more potent than other angiotensin receptor blockers in reducing blood pressure. However, its effect on the heart following myocardial infarction remains to be established. For the first time, we investigated the peroxisome proliferator-activated receptor-γ (PPAR-γ) agonistic and cardioprotective properties of azilsartan. Computational modeling studies of interactions between azilsartan and PPAR-γ revealed azilsartan as an agonist of PPAR-γ and showed the mechanism of azilsartan in cardioprotection. Our study compared the cardioprotective potential of telmisartan to that of azilsartan in a murine model of myocardial ischemia-reperfusion injury by comparing their antioxidant, ant apoptotic, antiinflammatory, mitogen-activated protein kinase (MAPK)-modulating ability, and PPAR-γ agonistic activity. Male Wistar rats were grouped into four to receive vehicle (dimethyl sulfoxide [0.05%] 2 ml/kg) telmisartan (10 mg/kg p.o.), azilsartan (10 mg/kg p.o.) or azilsartan with specific PPAR-γ blocker, GW 9662 for 28 days.Ischemia was induced for 45 min on the 29th day followed by 60 min of reperfusion.Telmisartan and azilsartan pretreatment significantly nearly normalized cardiac parameters and preserved structural changes. Both drugs inhibited oxidative burst, inflammation, as well as cell death by modulating apoptotic protein expression along with reduction in 4′,6-diamidino-2-phenylindole/terminal deoxynucleotidyl transferase dUTP nick end labeling-positive cells. An increment in pro-survival kinase ERK paralleled with a reduction in p38 and JNK was also revealed by MAPK pathway studies, after administration of these drugs. Interestingly, the aforementioned changes induced by both drugs were reversed by administration of the specific PPAR-γ antagonist, GW9662. However, we found that azilsartan upregulated PPAR-γ to a lesser extent as compared to telmisartan and the latter may be preferred in hypertensive patients at risk of myocardial infarction.

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Section: Discussionmentioning

confidence: 99%

Cardioprotective effects of azilsartan compared with that of telmisartan on an in vivo model of myocardial ischemia‐reperfusion injury

Garg

Khan

Malhotra

et al. 2021

J Biochem & Molecular Tox

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“…Both cTn-T and cK-MB are biomarkers of myocardial injury, and upregulation of these biomarkers is indicative of aggravated myocardial injury (36). It is well established that LVEF, FS, LVSP, LVEdP and ±dp/dtmax can be used to evaluate myocardial injury (37,38). Our study revealed that MALAT1 was highly expressed in HF patients and rats, and suppression of MALAT1 reduced the myocardial injury of HF rats.…”

Section: Discussionmentioning

confidence: 59%

Mechanism of long non‑coding RNA metastasis‑associated lung adenocarcinoma transcript 1 in lipid metabolism and inflammation in heart failure

et al. 2020

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“…CCl 4 is a well-documented hepatotoxin that induces acute liver injury by oxidative damage via its free radical metabolites [44][45][46]. TM can impede the glycosylation modification of newly synthesized proteins; therefore, it can cause damage to the ER function and induce ER stress in vivo and in vitro [47,48]. In agreement, CCl 4 induced ER ATF6 is critical for the adaptive response of ER stress, and it is associated with the pathogenesis of various liver conditions [49].…”

Section: Discussionmentioning

confidence: 95%

Downregulation of RIP3 Improves the Protective Effect of ATF6 in an Acute Liver Injury Model

Huang

Wan

Deng

et al. 2021

BioMed Research International

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Background. Activating transcription factor 6 (ATF6) and receptor-interacting protein 3 (RIP3) are important signaling proteins in endoplasmic reticulum (ER) stress and necroptosis, respectively. However, their regulatory relationship and clinical significance are unknown. We investigate the impact of ATF6 on RIP3 expression, and its role in hepatocyte necroptosis in an acute liver injury model. Methods. In vivo and in vitro experiments were carried out. LO2 cells were treated with thapsigargin (TG). In vivo, male BALB/c mice were treated with carbon tetrachloride (CCl4, 1 mL/kg) or tunicamycin (TM, 2 mg/kg). Then, the impact of ATF6 or RIP3 silencing on liver injury, hepatocyte necroptosis, and ER stress-related protein expression was examined. Results. TG induced ER stress and necroptosis and ATF6 and RIP3 expression in LO2 cells. The knockdown of ATF6 significantly decreased RIP3 expression ( p < 0.05 ) and increased ER stress and necroptosis. The downregulation of RIP3 significantly reduced necroptosis and ER stress ( p < 0.05 ). Similar results were observed in CCl4 or the TM-induced mouse model. The knockdown of ATF6 significantly decreased CCl4-induced RIP3 expression and increased liver injury, necroptosis, and ER stress in mice livers ( p < 0.05 ). In contrast, the downregulation of RIP3 significantly reduced liver injury, hepatocyte necroptosis, and ER stress. Conclusions. Hepatocyte ATF6 has multiple roles in acute liver injury. It reduces hepatocyte necroptosis via negative feedback regulation of ER stress. In addition, ATF6 can upregulate the expression of RIP3, which is not helpful to the recovery process. However, downregulating RIP3 reduces hepatocyte necroptosis by promoting the alleviation of ER stress. The findings suggest that RIP3 could be a plausible target for the treatment of liver injury.

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Preconditioning with endoplasmic reticulum stress alleviated heart ischemia/reperfusion injury via modulating IRE1/ATF6/RACK1/PERK and PGC-1α in diabetes mellitus

Cited by 27 publications

References 31 publications

Cardioprotective effects of azilsartan compared with that of telmisartan on an in vivo model of myocardial ischemia‐reperfusion injury

Cardioprotective effects of azilsartan compared with that of telmisartan on an in vivo model of myocardial ischemia‐reperfusion injury

Mechanism of long non‑coding RNA metastasis‑associated lung adenocarcinoma transcript 1 in lipid metabolism and inflammation in heart failure

Downregulation of RIP3 Improves the Protective Effect of ATF6 in an Acute Liver Injury Model

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