Matches in SemOpenAlex for { <https://semopenalex.org/work/W2896751904> ?p ?o ?g. }
- W2896751904 abstract "Connexin 43 (Cx43), a product of the GJA1 gene, is a gap junction protein facilitating intercellular communication between cardiomyocytes. Cx43 protects the heart from ischemic injury by mechanisms that are not well understood. GJA1 mRNA can undergo alternative translation, generating smaller isoforms in the heart, with GJA1-20k being the most abundant. Here, we report that ischemic and ischemia/reperfusion (I/R) injuries upregulate endogenous GJA1-20k protein in the heart, which targets to cardiac mitochondria and associates with the outer mitochondrial membrane. Exploring the functional consequence of increased GJA1-20k, we found that AAV9-mediated gene transfer of GJA1-20k in mouse hearts increases mitochondrial biogenesis while reducing mitochondrial membrane potential, respiration, and ROS production. By doing so, GJA1-20k promotes a protective mitochondrial phenotype, as seen with ischemic preconditioning (IPC), which also increases endogenous GJA1-20k in heart lysates and mitochondrial fractions. As a result, AAV9-GJA1-20k pretreatment reduces myocardial infarct size in mouse hearts subjected to in vivo ischemic injury or ex vivo I/R injury, similar to an IPC-induced cardioprotective effect. In conclusion, GJA1-20k is an endogenous stress response protein that induces mitochondrial biogenesis and metabolic hibernation, preconditioning the heart against I/R insults. Introduction of exogenous GJA1-20k is a putative therapeutic strategy for patients undergoing anticipated ischemic injury." @default.
- W2896751904 created "2018-10-26" @default.
- W2896751904 creator A5000482575 @default.
- W2896751904 creator A5004429108 @default.
- W2896751904 creator A5017223962 @default.
- W2896751904 creator A5030586659 @default.
- W2896751904 creator A5036486164 @default.
- W2896751904 creator A5041945728 @default.
- W2896751904 creator A5055364923 @default.
- W2896751904 creator A5068666913 @default.
- W2896751904 creator A5070202742 @default.
- W2896751904 date "2018-10-18" @default.
- W2896751904 modified "2023-10-11" @default.
- W2896751904 title "Stress response protein GJA1-20k promotes mitochondrial biogenesis, metabolic quiescence, and cardioprotection against ischemia/reperfusion injury" @default.
- W2896751904 cites W1559427936 @default.
- W2896751904 cites W1978451664 @default.
- W2896751904 cites W1979047809 @default.
- W2896751904 cites W1980177930 @default.
- W2896751904 cites W1980756616 @default.
- W2896751904 cites W1986649427 @default.
- W2896751904 cites W1987230422 @default.
- W2896751904 cites W1991649249 @default.
- W2896751904 cites W1995917550 @default.
- W2896751904 cites W1999526484 @default.
- W2896751904 cites W2019488837 @default.
- W2896751904 cites W2022135851 @default.
- W2896751904 cites W2026731864 @default.
- W2896751904 cites W2031426329 @default.
- W2896751904 cites W2035390870 @default.
- W2896751904 cites W2035968737 @default.
- W2896751904 cites W2036933116 @default.
- W2896751904 cites W2046967306 @default.
- W2896751904 cites W2049111653 @default.
- W2896751904 cites W2051273609 @default.
- W2896751904 cites W2052311383 @default.
- W2896751904 cites W2053281611 @default.
- W2896751904 cites W2054526264 @default.
- W2896751904 cites W2055820092 @default.
- W2896751904 cites W2068007378 @default.
- W2896751904 cites W2068048197 @default.
- W2896751904 cites W2068603783 @default.
- W2896751904 cites W2071179641 @default.
- W2896751904 cites W2076543078 @default.
- W2896751904 cites W2077660651 @default.
- W2896751904 cites W2085367705 @default.
- W2896751904 cites W2091296592 @default.
- W2896751904 cites W2111715328 @default.
- W2896751904 cites W2112944877 @default.
- W2896751904 cites W2119073166 @default.
- W2896751904 cites W2121077787 @default.
- W2896751904 cites W2125302529 @default.
- W2896751904 cites W2126337135 @default.
- W2896751904 cites W2127430952 @default.
- W2896751904 cites W2133272735 @default.
- W2896751904 cites W2135515146 @default.
- W2896751904 cites W2136290454 @default.
- W2896751904 cites W2142508159 @default.
- W2896751904 cites W2144719264 @default.
- W2896751904 cites W2146217294 @default.
- W2896751904 cites W2146818927 @default.
- W2896751904 cites W2148425490 @default.
- W2896751904 cites W2148546947 @default.
- W2896751904 cites W2153762721 @default.
- W2896751904 cites W2155347215 @default.
- W2896751904 cites W2155643523 @default.
- W2896751904 cites W2155698194 @default.
- W2896751904 cites W2158363851 @default.
- W2896751904 cites W2160490742 @default.
- W2896751904 cites W2164721799 @default.
- W2896751904 cites W2167309123 @default.
- W2896751904 cites W2168079862 @default.
- W2896751904 cites W2168165271 @default.
- W2896751904 cites W2170347547 @default.
- W2896751904 cites W2175371769 @default.
- W2896751904 cites W2190642228 @default.
- W2896751904 cites W2252627291 @default.
- W2896751904 cites W2275210540 @default.
- W2896751904 cites W2365330985 @default.
- W2896751904 cites W2558901399 @default.
- W2896751904 cites W2680776698 @default.
- W2896751904 cites W2739882984 @default.
- W2896751904 cites W2740802860 @default.
- W2896751904 cites W2763961597 @default.
- W2896751904 cites W2767344017 @default.
- W2896751904 cites W2784192559 @default.
- W2896751904 cites W2789860518 @default.
- W2896751904 cites W2792845052 @default.
- W2896751904 cites W2893248496 @default.
- W2896751904 cites W82234966 @default.
- W2896751904 doi "https://doi.org/10.1172/jci.insight.121900" @default.
- W2896751904 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/6237442" @default.
- W2896751904 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/30333316" @default.
- W2896751904 hasPublicationYear "2018" @default.
- W2896751904 type Work @default.
- W2896751904 sameAs 2896751904 @default.
- W2896751904 citedByCount "58" @default.
- W2896751904 countsByYear W28967519042018 @default.
- W2896751904 countsByYear W28967519042019 @default.
- W2896751904 countsByYear W28967519042020 @default.
- W2896751904 countsByYear W28967519042021 @default.