Qvit 2022 Pharmaceuticals (Basel)

From Bioblast
Publications in the MiPMap
Qvit N, Lin AJ, Elezaby A, Ostberg NP, Campos JC, Ferreira JCB, Mochly-Rosen D (2022) A selective inhibitor of cardiac troponin I phosphorylation by delta protein kinase C (Ξ΄PKC) as a treatment for ischemia-reperfusion injury. https://doi.org/10.3390/ph15030271

Β» Pharmaceuticals (Basel) 15:271. PMID: 35337069 Open Access

Qvit Nir,  Lin Amanda J,  Elezaby Aly,  Ostberg Nicolai P,  Campos Juliane C,  Ferreira Julio CB,  Mochly-Rosen Daria (2022) Pharmaceuticals (Basel)

Abstract: 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 (Ξ΄PKC) with a pan-inhibitor (Ξ΄V1-1) 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 Ξ΄PKC during reperfusion. Here, we describe a rationally-designed, selective, high-affinity, eight amino acid peptide that inhibits cTnI's interaction with, and phosphorylation by, Ξ΄PKC (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 Ξ΄PKC phosphorylation of cTnI is critical in IR injury, and that a cTnI/Ξ΄PKC interaction inhibitor should be considered as a therapeutic target to reduce cardiac injury after myocardial infarction. β€’ Keywords: Cardiac ischemia-reperfusion injury, Cardiac troponin I, Peptides β€’ Bioblast editor: Plangger M

Labels: MiParea: Respiration, Pharmacology;toxicology 

Stress:Ischemia-reperfusion  Organism: Rat  Tissue;cell: Heart  Preparation: Isolated mitochondria 

Coupling state: LEAK, OXPHOS  Pathway: NS  HRR: Oxygraph-2k, O2k-Fluorometer 

2022-12, AmR 

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