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- W3010092913 abstract "Abstract A splice site mutation in the canine pyruvate dehydrogenase kinase 4 ( PDK4 ) gene has been shown to be associated with the development of dilated cardiomyopathy (DCM) in Doberman Pinchers (DPs). Subsequent studies have successfully demonstrated the use of dermal fibroblasts isolated from DPs as models for PDK4 deficiency and have shown activation of the intrinsic (mitochondrial mediated) apoptosis pathway in these cells under starvation conditions. For this study, we sought to further explore the functional consequences of PDK4 deficiency in DP fibroblasts representing PDK4 wt/wt , PDK4 wt/del , and PDK4 del/del genotypes. Our results show that starvation conditions cause increased perinuclear localization of mitochondria and decreased cell proliferation, altered expression levels of pyruvate dehydrogenase phosphatase (PDP) and pyruvate dehydrogenase (PDH), dramatically increased PDH activity, and an impaired response to mitochondrial stress in affected cells. In sum, these results show the broad impact of PDK4 deficiency and reveal mechanistic pathways used by these cells in an attempt to compensate for the condition. Our data help to elucidate the mechanisms at play in this extremely prevalent DP disorder and provide further support demonstrating the general importance of metabolic flexibility in cell health." @default.
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- W3010092913 date "2020-03-03" @default.
- W3010092913 modified "2023-10-10" @default.
- W3010092913 title "Functional Consequences of PDK4 Deficiency in Doberman Pinscher Fibroblasts" @default.
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- W3010092913 doi "https://doi.org/10.1038/s41598-020-60879-6" @default.
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