pPolyHb protects myocardial H9C2 cells against ischemia-reperfusion injury by regulating the Pink1-Parkin-mediated mitochondrial autophagy pathway

Zhu, Wenjin; Liu, Fang; Wang, Li; Yang, Bo; Bai, Yujia; Huang, Yanzhi; Li, Wei; Yue-min, Yuan; Chen, Chao; Zhu, Hongli

doi:10.1080/21691401.2019.1594243

Cited by 23 publications

(12 citation statements)

References 19 publications

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“…Interestingly, BI1 reconstitution confers resistance for tubule cells to AKI-induced mitochondrial damage. Consistent with previous studies 45-48, the protective mechanisms exerted by BI1 in AKI involves elimination of cellular ROS, interruption of mitochondrial fission, and inhibition of mitochondrial apoptosis. Besides, based on our results, BI1 also plays unforeseen roles in sustaining mtDNA copy/transcription, mitochondrial respiration and mitophagy.…”

Section: Discussionsupporting

confidence: 89%

Bax inhibitor 1 preserves mitochondrial homeostasis in acute kidney injury through promoting mitochondrial retention of PHB2

Wang¹,

Zhu²,

Li³

et al. 2020

Theranostics

117

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Bax inhibitor-1 (BI1) conveys anti-apoptotic signals for mitochondria while prohibitin 2 (PHB2) is implicated in sustaining mitochondrial morphology and function. However, their regulatory roles in acute kidney injury (AKI) are largely unknown.Methods: In human patients with AKI, levels of BI1 in urine and plasma were determined using ELISA. An experimental model of AKI was established using ATP depletion-mediated metabolic stress and ischemia-reperfusion injury (IRI) in primary tubule cells and BI1 transgenic mice, respectively. Western blots, ELISA, qPCR, immunofluorescence, RNA silencing, and domain deletion assay were employed to evaluate the roles of BI1 and PHB2 in the preservation of mitochondrial integrity.Results: Levels of BI1 in urine and plasma were decreased in patients with AKI and its expression correlated inversely with renal function. However, reconstitution of BI1 in a murine AKI model was capable of alleviating renal failure, inflammation and tubular death. Further molecular scrutiny revealed that BI1 preserved mitochondrial genetic integrity, reduced mitochondrial oxidative stress, promoted mitochondrial respiration, inhibited excessive mitochondrial fission, improved mitophagy and suppressed mitochondrial apoptosis. Intriguingly, levels of the mitochondria-localized PHB2 were sustained by BI1 and knockdown of PHB2 abolished the mitochondrial- and renal- protective properties of BI1. Furthermore, BI1 promoted PHB2 retention within mitochondria through direct interaction with cytoplasmic PHB2 to facilitate its mitochondrial import. This was confirmed by the observation that the C-terminus of BI1 and the PHB domain of PHB2 were required for the BI1-PHB2 cross-linking.Conclusion: Our data have unveiled an essential role of BI1 as a master regulator of renal tubule function through sustaining mitochondrial localization of PHB2, revealing novel therapeutic promises against AKI.

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Section: Discussionsupporting

confidence: 89%

Bax inhibitor 1 preserves mitochondrial homeostasis in acute kidney injury through promoting mitochondrial retention of PHB2

Wang¹,

Zhu²,

Li³

et al. 2020

Theranostics

117

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“…58 It has been reported that moderate mitochondrial serine/threonine protein kinase Pink1 and E3 ubiquitin protein ligase Parkin could effectively remove excess ROS and abnormal mitochondria to maintain cell stability, and resist apoptosis through mitochondrial phagocytosis. 60–62 On the other hand, during the process of mitochondrial autophagy, the damaged mitochondria are encapsulated in a bilayer membrane structure to form auto phagosomes. 63 If the scavenging reaction of auto phagosomes exceeds the protective threshold under the influence of external factors, mitochondrial autophagy will continue to occur and aggravate cell damage, leading to cell apoptosis.…”

Section: Discussionmentioning

confidence: 99%

Study of the mechanism of mitochondrial division and mitochondrial autophagy in the male reproductive toxicity induced by nickel nanoparticles

Liu

Lü²,

Dong

et al. 2022

Nanoscale

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“…The contraction and functioning of the heart are mainly dependent on mitochondria to provide energy. emerging evidence has suggested that the accumulation of dysfunctional mitochondria may result in increased intracellular roS, thus leading to cardiac dysfunction (42). Mitophagy is an effective process that can remove damaged mitochondria and maintain mitochondrial function (43).…”

Section: Discussionmentioning

confidence: 99%

Salvianolic acid B alleviates myocardial ischemic injury by promoting mitophagy and inhibiting activation of the NLRP3 inflammasome

Wang

et al. 2020

Mol Med Rep

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ischemic heart disease is a major cause of mortality and disability worldwide. Salvianolic acid B (Sal B) is one of the main water-soluble components of Salvia miltiorrhiza Bge. numerous studies have demonstrated that Sal B could exert significant anti-inflammatory and cardiovascular protective effects; however, the underlying mechanisms remain unclear. To elucidate the association between myocardial ischemia and inflammation, and to develop effective protective drugs, a rat model of myocardial ischemia was induced using isoproterenol (iSo) and an inflammation model in H9c2 cells was induced with lipopolysaccharide + adenosine triphosphate. Both of these models were treated with different concentrations of Sal B (5, 10 and 15 mg/kg in vivo; 1, 5 and 25 µM in vitro). In vivo, the serum levels of creatine kinase isoenzyme MB, glutamic oxaloacetic transaminase and il-1β, the cardiac function and the mrna expression levels of nlr family pyrin domain-containing 3 (nlrP3) inflammasome components were evaluated using ELISAs, an electrocardiogram, hematoxylin and eosin staining and reverse transcription-quantitative Pcr, respectively. The results demonstrated that treatment with Sal B markedly alleviated the acute myocardial ischemic injury induced by hypodermic injection of iSo in rats. In vitro, the results of reactive oxygen species (roS) detection, Jc-1 staining, western blotting and Tunel assays showed that Sal B treatment significantly inhibited intracellular roS production, increased the mitochondrial membrane potential, regulated the expression of mitophagy-related proteins, inhibited the activation of the NLRP3 inflammasome and inhibited apoptosis in H9C2 cells. in conclusion, these findings indicated that Sal B exerted protective effects against myocardial ischemic injury by promoting mitophagy and maintaining mitochondrial function.

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pPolyHb protects myocardial H9C2 cells against ischemia-reperfusion injury by regulating the Pink1-Parkin-mediated mitochondrial autophagy pathway

Abstract: Zhu (2019) pPolyHb protects myocardial H9C2 cells against ischemia-reperfusion injury by regulating the Pink1-Parkin-mediated mitochondrial autophagy pathway,

Cited by 23 publications

References 19 publications

Bax inhibitor 1 preserves mitochondrial homeostasis in acute kidney injury through promoting mitochondrial retention of PHB2

Bax inhibitor 1 preserves mitochondrial homeostasis in acute kidney injury through promoting mitochondrial retention of PHB2

Study of the mechanism of mitochondrial division and mitochondrial autophagy in the male reproductive toxicity induced by nickel nanoparticles

Salvianolic acid B alleviates myocardial ischemic injury by promoting mitophagy and inhibiting activation of the NLRP3 inflammasome

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