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• W2893553693 abstract "Abstract Background and Purpose Double‐stranded RNA‐dependent protein kinase (PKR) is a critical regulator of apoptosis, oxidative stress, and inflammation under hyperlipidemic and insulin resistance conditions. Saturated free fatty acids, such as palmitic acid (PA), are known inducers of apoptosis in numerous cell types. However, the underlying molecular mechanism is not fully understood. The aim of the present study was to examine the effect of PA on cultured rat H9C2 cardiac myocytes cells and to investigate the PKR mediated harmful effects of PA in vitro in cultured cardiomyocytes. Experimental Approach PKR expression was determined by immunofluorescence and immunoblotting. Oxidative stress and apoptosis were determined by flow cytometry and assay kits. The expression of different gene markers of apoptosis, oxidative stress, and inflammation were measured by Western blot analysis and reverse transcription polymerase chain reaction. Key Results PKR expression, reactive oxygen species levels as well as apoptosis were increased in PA‐treated cultured H9C2 cardiomyocytes. The harmful effects of PA were attenuated by a selective PKR inhibitor, C16. Moreover, we observed that upregulation of c‐Jun N‐terminal kinase (JNK), nuclear factor‐kB (NF‐kB) and NACHT, LRR and PYD domains‐containing protein 3 (NLRP3) pathways is associated with increased expression of interleukin 6 and tumor necrosis factor‐α in PA‐treated cardiomyocytes and attenuation by a selective PKR inhibitor. Conclusion and Implications Our study reports, for the first time, that PKR‐mediated harmful effects of PA in cultured cardiomyocytes via activation of JNK, NF‐kB, and NLRP3 pathways. Inhibition of PKR is one of the possible mechanistic approaches to inhibit inflammation, oxidative stress, and apoptosis in lipotoxicity‐induced cardiomyocyte damage." @default.
• W2893553693 created "2018-10-05" @default.
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• W2893553693 date "2018-09-27" @default.
• W2893553693 modified "2023-10-02" @default.
• W2893553693 title "Inhibition of protein kinase R protects against palmitic acid–induced inflammation, oxidative stress, and apoptosis through the JNK/NF‐kB/NLRP3 pathway in cultured H9C2 cardiomyocytes" @default.
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• W2893553693 doi "https://doi.org/10.1002/jcb.27643" @default.
• W2893553693 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/30259999" @default.
• W2893553693 hasPublicationYear "2018" @default.
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