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• W2897526367 endingPage "F53" @default.
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• W2897526367 abstract "Identifying pathways related to renal cold storage (CS) that lead to renal damage after transplantation (Tx) will help us design novel pathway-specific therapies to improve graft outcome. Our recent report showed that mitochondrial function was compromised after CS alone, and this was exacerbated when CS was combined with Tx (CS/Tx). The goal of this study was to determine whether the proteasome exacerbates mitochondrial dysfunction after CS/Tx. We exposed the kidneys of male Lewis rats (in vivo) and rat renal proximal tubular (NRK) cells (in vitro) to CS/Tx or rewarming (CS/RW), respectively. To compare CS-induced effects, in vivo kidney Tx without CS exposure (autotransplantation; ATx) was also used. Our study provides the first evidence that the chymotrypsin-like (ChT-L) peptidase activity of the proteasome declined only after CS/Tx or CS/RW, but not after CS or ATx. Interestingly, key mitochondrial proteins involved with respiration [succinate dehydrogenase complex, subunit A (SDHA), a complex II subunit, and ATP5B, an ATP synthase/complex V subunit] were detected in the detergent-insoluble fraction after CS/Tx or CS/RW, with compromised complex V activity. Pharmacological inhibition of ChT-L activity in NRK cells decreased the activity of mitochondrial complexes I, II, and V and also increased the levels of SDHA and ATP5B in the insoluble fraction. On the other hand, inhibiting mitochondrial respiration in NRK cells with antimycin A compromised ChT-L function and increased the amounts of SDHA and ATP5B in the insoluble fraction. Our results suggest that mitochondrial respiratory dysfunction during CS precedes compromised ChT-L function after CS/Tx and proteasome dysfunction further alters mitochondrial protein homeostasis and decreases respiration in the kidneys after CS/Tx. Therefore, therapeutics that preserve mitochondrial and proteasome function during CS may provide beneficial outcomes following transplantation." @default.
• W2897526367 created "2018-10-26" @default.
• W2897526367 creator A5018323619 @default.
• W2897526367 creator A5021164517 @default.
• W2897526367 creator A5034170524 @default.
• W2897526367 date "2019-01-01" @default.
• W2897526367 modified "2023-10-13" @default.
• W2897526367 title "Renal cold storage followed by transplantation impairs proteasome function and mitochondrial protein homeostasis" @default.
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• W2897526367 doi "https://doi.org/10.1152/ajprenal.00316.2018" @default.
• W2897526367 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/6383197" @default.
• W2897526367 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/30303714" @default.
• W2897526367 hasPublicationYear "2019" @default.
• W2897526367 type Work @default.

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