IndraLab

Statements

Nitric oxide inhibits USP5. 11 / 16
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"NO inhibits isopeptidase T activity in a concentration dependent manner."
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"Furthermore, it is possible that NO may prevent protein breakdown by affecting the activity of isopeptidase T through S nitrosylation of active site cysteines."
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"To determine if NO inhibits isopeptidase T activity via modification of cysteine thiol groups, DTT (5 mmol/L) was added to the activity assay before SNAP (1000 mumol/L)."
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"This correlation between the effect of NO on isopeptidase T activity and the presence of S nitrosylated isopeptidase T is further strengthened by evidence that NO inhibits isopeptidase T activity in a concentration dependent fashion in vitro."
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"NO inhibited recombinant isopeptidase T activity by 82.8% (t = 60 minutes, P <.001 vs control)."
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"We demonstrate here that NO inhibits the activity, but not levels, of isopeptidase T in VSMC in vitro, while decreasing its levels and increasing ubiquitinated proteins in the vasculature in vivo."
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"We investigated the effects of NO on isopeptidase T and showed that NO inhibits recombinant isopeptidase T activity, increases S nitrosylated isopeptidase T levels in vascular smooth muscle cells, and, after balloon injury in vivo, decreases isopeptidase T levels and increases ubiquitinated proteins."
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"We show, for the first time, that NO inhibits isopeptidase T activity in the vasculature, most likely by S nitrosylation of a critical cysteine residue, a common mechanism by which NO regulates the activity of cysteine proteases."
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"As NO can cause S nitrosylation of active-site cysteines, we hypothesize that NO inhibits isopeptidase T activity through S nitrosylation."
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"We expect that these experiments would indicate that NO decreases isopeptidase T activity in vivo, which would lead to ubiquitin-proteasome pathway inhibition as a result of accumulation of proteins with unprocessed K48 linked polyubiquitin chains."
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"Dithiothreitol and glutathione (5 mmol/L) both significantly reversed NO mediated inhibition of isopeptidase T activity (P <.001)."
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