Inhibition of Phosphoglycerate Mutase 5 Reduces Necroptosis in Rat Hearts Following Ischemia/Reperfusion Through Suppression of Dynamin-Related Protein 1

She, Lang; Tu, Hua; Zhang, Yin Zhuang; Tang, Li; Li, Nian Sheng; Lin, Qingshan; Liu, Bin; Li, Qingjie; Luo, Xiaohua; Peng, Jun

doi:10.1007/s10557-018-06848-8

Cited by 49 publications

(46 citation statements)

References 27 publications

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“…Thirdly, activity of DRP1 is regulated by phosphorylation at different sites on serine. There are at least three phosphorylation sites on Ser616, Ser637 and Ser656 of DRP1 with different (even opposing) effects to regulate mitochondrial functions . However, the effect of NaHS on phosphorylation of DRP1 was unknown in the present study.…”

Section: Discussionmentioning

confidence: 67%

Exogenous hydrogen sulphide supplement accelerates skin wound healing via oxidative stress inhibition and vascular endothelial growth factor enhancement

Hua

et al. 2019

Experimental Dermatology

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Hydrogen sulphide (H2S) is an important gasotransmitter with several physiological functions. However, the roles and the detailed mechanisms of H2S on skin wound healing are not known well. In the present study, 129S1/SvImJ mice were intraperitoneally injected with NaHS (50 μmol/kg/d) for 2 weeks. Then, a round wound of 6 mm diameter with depth into the dermis was made. The skin wound area, blood perfusion, superoxide production, malondialdehyde (MDA) levels, total antioxidant capacity (T‐AOC), expression of vascular endothelial growth factor (VEGF), dynamin‐related protein 1 (DRP1) and optic atrophy 1 (OPA1) were measured. After NaHS (50 μmol/L) pre‐administration for 4 hours, cell migration rate, DRP1, OPA1 and α–smooth muscle actin (α‐SMA) expression, superoxide production and mitochondrial membrane potential in primary skin fibroblasts were measured. Tube formation in human umbilical vein endothelial cells (HUVECs) and cell migration in human keratinocytes were also measured. The results showed that NaHS pretreatment significantly accelerated wound healing and improved blood flow in the wound after operation. NaHS increased VEGF expression in the wound and promoted tube formation in HUVECs. Meanwhile, NaHS attenuated reactive oxygen species (ROS) production, suppressed MDA level but restored T‐AOC in the wound. NaHS also promoted skin fibroblasts migration and α‐SMA expression after scratch. Moreover, NaHS alleviated ROS, increased mitochondrial membrane potential, decreased DRP1 but enhanced OPA1 expression in skin fibroblasts after scratch. NaHS also accelerated human keratinocytes migration after scratch. Taken together, exogenous H2S supplementary accelerated the skin wound healing, which might be related to oxidative stress inhibition and VEGF enhancement.

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Section: Discussionmentioning

confidence: 67%

Exogenous hydrogen sulphide supplement accelerates skin wound healing via oxidative stress inhibition and vascular endothelial growth factor enhancement

Hua

et al. 2019

Experimental Dermatology

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“…RIPK3 is known to be necessary for MLKL‐mediated necroptosis, as knocking down RIPK3 prevented trimerization of MLKL 32 . In addition to the disruption of plasma membrane, RIPK3 was translocated to the mitochondrial membrane, leading to mitochondrial fission via the activation of Dynamin‐related protein 1 (Drp1) 24,26,30 . Drp1, a mitochondrial fission regulator, is phosphorylated at serine 616 and dephosphorylated at serine 637 residues as a consequence of reoxygenation/reperfusion injury, resulting in mitochondrial fragmentation 34 .…”

Section: Introductionmentioning

confidence: 99%

“…Genetic deletion of CypD rendered the mice resistant to necrotic but not apoptotic cell death 46 . Upregulation of PGAM5 was associated with increased CypD‐mediated mPTP opening 30 and Drp1‐mediated mitochondrial fragmentation 26 . The activity of PGAM5, along with subsequent RIPK3‐mediated mPTP‐driven necrosis, could be suppressed by Kelch‐like ECH‐associated protein 1 (Keap1) 39 .…”

Section: Introductionmentioning

confidence: 99%

The role of RIPK3‐regulated cell death pathways and necroptosis in the pathogenesis of cardiac ischaemia‐reperfusion injury

2020

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Despite advancements in management of acute myocardial infarction, this disease remains one of the leading causes of death. Timely reestablishment of epicardial coronary blood flow is the cornerstone of therapy; however, substantial amount of damage can occur as a consequence of cardiac ischaemia/reperfusion (I/R) injury. It has been previously proposed that the pathway leading to major cell death, apoptosis, is responsible for cardiac I/R injury. Nevertheless, there is compelling evidence to suggest that necroptosis, a programmed necrosis, contributes remarkably to both myocardial injury and microcirculatory dysfunction following cardiac I/R injury. Receptor‐interacting protein kinase 1 (RIPK1), RIPK3, and mixed‐lineage kinase domain‐like pseudokinase (MLKL) are shown as the major mediators of necroptosis. In addition to the traditional perception that RIPK1/RIPK3/MLKL‐dependent plasma membrane rupture is fundamental to this process, several RIPK3‐related pathways such as endoplasmic reticulum stress and mitochondrial fragmentation have also been implicated in cardiac I/R injury. In this review, reports from both in vitro and in vivo studies regarding the roles of necroptosis and RIPK3‐regulated necrosis in cardiac I/R injury have been collectively summarized and discussed. Furthermore, reports on potential interventions targeting these processes to attenuate cardiac I/R insults to the heart have been presented in this review. Future investigations adding to the knowledge obtained from these previous studies are needed in the pursuit of discovering the most effective pharmacological agent to improve cardiac I/R outcomes.

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“…An increase was also seen in the mitochondrial membrane protein PGAM5 (phosphoglycerate mutase family member 5), an atypical Ser/Thr phosphatase that dephosphorylates and activates the mitochondrial fission protein DRP1 . Furthermore, PGAM5 knockdown suppressed the generation of ROS and preserved ΔΨ m , implicating mitochondria in the process of necroptosis . In a similar model of H9c2 subjected to HR, siRNA targeting RIP3 was shown to prevent mitochondrial fragmentation and necroptosis, by preventing activation of DRP1, again suggesting a link between necroptosis and mitochondria …”

Section: Necroptosismentioning

confidence: 89%

“…Necroptosis has been seen to occur in both H9c2 cardiomyoblasts subjected to hypoxia/reoxygenation (HR) and in vivo rat hearts subject to IR, as evidenced by increased levels of RIP1, RIP3 and MLKL . An increase was also seen in the mitochondrial membrane protein PGAM5 (phosphoglycerate mutase family member 5), an atypical Ser/Thr phosphatase that dephosphorylates and activates the mitochondrial fission protein DRP1 . Furthermore, PGAM5 knockdown suppressed the generation of ROS and preserved ΔΨ m , implicating mitochondria in the process of necroptosis .…”

Section: Necroptosismentioning

confidence: 99%

Mitochondrial and mitochondrial‐independent pathways of myocardial cell death during ischaemia and reperfusion injury

Davidson

Adameová

Barile³

et al. 2020

J Cellular Molecular Medi

135

108

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Acute myocardial infarction causes lethal injury to cardiomyocytes during both ischaemia and reperfusion (IR). It is important to define the precise mechanisms by which they die in order to develop strategies to protect the heart from IR injury. Necrosis is known to play a major role in myocardial IR injury. There is also evidence for significant myocardial death by other pathways such as apoptosis, although this has been challenged. Mitochondria play a central role in both of these pathways of cell death, as either a causal mechanism is the case of mitochondrial permeability transition leading to necrosis, or as part of the signalling pathway in mitochondrial cytochrome c release and apoptosis. Autophagy may impact this process by removing dysfunctional proteins or even entire mitochondria through a process called mitophagy. More recently, roles for other programmed mechanisms of cell death such as necroptosis and pyroptosis have been described, and inhibitors of these pathways have been shown to be cardioprotective. In this review, we discuss both mitochondrial and mitochondrial‐independent pathways of the major modes of cell death, their role in IR injury and their potential to be targeted as part of a cardioprotective strategy. This article is part of a special Issue entitled ‘Mitochondria as targets of acute cardioprotection’ and emerged as part of the discussions of the European Union (EU)‐CARDIOPROTECTION Cooperation in Science and Technology (COST) Action, CA16225.

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Inhibition of Phosphoglycerate Mutase 5 Reduces Necroptosis in Rat Hearts Following Ischemia/Reperfusion Through Suppression of Dynamin-Related Protein 1

Cited by 49 publications

References 27 publications

Exogenous hydrogen sulphide supplement accelerates skin wound healing via oxidative stress inhibition and vascular endothelial growth factor enhancement

Exogenous hydrogen sulphide supplement accelerates skin wound healing via oxidative stress inhibition and vascular endothelial growth factor enhancement

The role of RIPK3‐regulated cell death pathways and necroptosis in the pathogenesis of cardiac ischaemia‐reperfusion injury

Mitochondrial and mitochondrial‐independent pathways of myocardial cell death during ischaemia and reperfusion injury

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