Mitophagy Regulation Following Myocardial Infarction

Turkieh, Annie; Masri, Yara El El; Pinet, Florence; Dubois‐Deruy, Emilie

doi:10.3390/cells11020199

Cited by 32 publications

(18 citation statements)

References 115 publications

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“…Mitochondrial dysfunction is a key feature of IR injury [ 16 , 17 , 18 , 19 , 20 , 21 , 22 ], and the pan-inhibition of δPKC, with δV1-1, prevents IR-induced increases in mitochondrial oxidant production, and decreases in ATP levels [ 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 ]. However, the mechanism by which δPKC causes mitochondrial dysfunction, and the protein substrate that mediates it, have not been identified.…”

Section: Resultsmentioning

confidence: 99%

A Selective Inhibitor of Cardiac Troponin I Phosphorylation by Delta Protein Kinase C (δPKC) as a Treatment for Ischemia-Reperfusion Injury

et al. 2022

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Myocardial infarction is the leading cause of cardiovascular mortality, with myocardial injury occurring during ischemia and subsequent reperfusion (IR). We previously showed that the inhibition of protein kinase C delta (δPKC) with a pan-inhibitor (δV1-1) mitigates myocardial injury and improves mitochondrial function in animal models of IR, and in humans with acute myocardial infarction, when treated at the time of opening of the occluded blood vessel, at reperfusion. Cardiac troponin I (cTnI), a key sarcomeric protein in cardiomyocyte contraction, is phosphorylated by δPKC during reperfusion. Here, we describe a rationally-designed, selective, high-affinity, eight amino acid peptide that inhibits cTnI’s interaction with, and phosphorylation by, δPKC (ψTnI), and prevents tissue injury in a Langendorff model of myocardial infarction, ex vivo. Unexpectedly, we also found that this treatment attenuates IR-induced mitochondrial dysfunction. These data suggest that δPKC phosphorylation of cTnI is critical in IR injury, and that a cTnI/δPKC interaction inhibitor should be considered as a therapeutic target to reduce cardiac injury after myocardial infarction.

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Section: Resultsmentioning

confidence: 99%

A Selective Inhibitor of Cardiac Troponin I Phosphorylation by Delta Protein Kinase C (δPKC) as a Treatment for Ischemia-Reperfusion Injury

et al. 2022

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“…As mentioned above, increasing evidence suggests that modulation of mitophagy plays a pivotal role during myocardial IRI (11), and it may become a novel target for cardioprotection. The PINK1/Parkin signaling pathway is the most recognized pathway leading to mitophagy in mammalian cells (29). PINK1, a serine/threonine kinase, is imported from the cytoplasm to the inner mitochondrial membrane in healthy mitochondria.…”

Section: Discussionmentioning

confidence: 99%

Dl-3-n-butylphthalide attenuates myocardial ischemia reperfusion injury by suppressing oxidative stress and regulating cardiac mitophagy via the PINK1/Parkin pathway in rats

Zhang¹,

Zheng²,

Fu³

et al. 2022

J Thorac Dis

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Background: Acute myocardial infarction (AMI) is one of the leading causes of mortality worldwide.Undesirable myocardial damage may occur during reperfusion of the ischemic myocardium, and this is known as "ischemic reperfusion injury" (IRI). Currently, there are few effective drugs to alleviate IRI. Dl-3-n-butylphthalide (NBP) is recommended for the treatment of acute ischemic stroke in China. This study investigated the effects of NBP on IRI and its underlying mechanisms. Methods:The left anterior descending (LAD) coronary arteries of rats were occluded for 30 minutes and reperfused for 6 hours to establish the ischemia/reperfusion (I/R) model. NBP was administered intraperitoneally 2 hours before modeling and immediately after reperfusion. At 6 hours after reperfusion, 2,3,5-triphenyltetrazolium chloride (TTC) staining, enzyme-linked immunosorbent assay (ELISA), oxidative stress index, myocardial injury index, hematoxylin and eosin (HE) staining, transmission electron microscopy (TEM), real-time polymerase chain reaction (PCR), immunofluorescence staining, and Western blot analyses were performed to investigate the protective effects of NBP against IRI.Results: In the rat I/R model, NBP remarkably reduced the myocardial infarct size, alleviated myocardial injury and oxidative stress, improved the pathological alteration of cardiomyocytes and mitochondria, and upregulated mitophagy. In addition, the study demonstrated that the protective effects of NBP against IRI involved mitophagy mediated by the PTEN-induced putative kinase protein-1 (PINK1)/Parkin signaling pathway.Conclusions: NBP was able to protect the myocardium from IRI in rats through inhibiting oxidative stress and activating mitophagy, mediated by the PINK1/Parkin pathway.

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“…Studies have shown that under normal conditions, PINK1 enters the inner membrane with the help of protein transporters and is continuously cleaved and decomposed by proteins in the inner membrane of mitochondria, and finally transported to the cytoplasm [28]. However, in dysfunctional mitochondria, the cutting process of PINK1 is stopped and accumulates in the outer membrane of mitochondria [29].…”

Section: Discussionmentioning

confidence: 99%

Transcutaneous Electrical Acupoint Stimulation Ameliorates Cognitive Function through PINK1/Parkin Mediated Mitophagy in VD Rats

Wen

et al. 2022

Evidence-Based Complementary and Alternative Medicine

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In this study, we investigated whether transcutaneous electrical acupoint stimulation (TEAS) could improve cognitive function in VD rats by regulating PINK1/Parkin-mediated mitophagy. VD rat model was prepared by modified 2-vessel occlusion (2-VO) and randomly divided into four groups: Sham group (Sham), Model group (Model), TEAS group (TEAS), and TEAS + 3-MA group (T +3 -MA). In the T +3 -MA group, autophagy inhibitor (3-MA) was injected into the lateral ventricle. After modeling, Y maze (YM), new object recognition test (NORT), Morris water maze (MWM), immunofluorescence, and Western blot were used to observe the effects of TEAS on VD rats. Behavioral experiments revealed that TEAS effectively improved the learning and memory ability of VD rats. Immunofluorescence results showed that TEAS could upregulate LC3 expression. Western blot results showed that TEAS upregulated the expression of PINK1, Parkin, and LC3-II, and downregulated the expression of LC3-I and p62 in VD rats. T +3 -MA group shows the opposite trend to TEAS group. This study demonstrates that TEAS ameliorates cognitive function through PINK1/Parkin-mediated mitophagy in VD rats.

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Mitophagy Regulation Following Myocardial Infarction

Cited by 32 publications

References 115 publications

A Selective Inhibitor of Cardiac Troponin I Phosphorylation by Delta Protein Kinase C (δPKC) as a Treatment for Ischemia-Reperfusion Injury

A Selective Inhibitor of Cardiac Troponin I Phosphorylation by Delta Protein Kinase C (δPKC) as a Treatment for Ischemia-Reperfusion Injury

Dl-3-n-butylphthalide attenuates myocardial ischemia reperfusion injury by suppressing oxidative stress and regulating cardiac mitophagy via the PINK1/Parkin pathway in rats

Transcutaneous Electrical Acupoint Stimulation Ameliorates Cognitive Function through PINK1/Parkin Mediated Mitophagy in VD Rats

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