IndraLab

Statements

Probucol decreases the amount of KCNH2. 10 / 10
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"Probucol, a cholesterol lowering drug, induces LQTs by inhibiting the expression of the hERG channel."
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"To demonstrate further whether CCh impeded probucol induced reduction of 155 kDa hERG expression was the result of alteration of p-Nedd4-2, we detected the p-Nedd4-2 expression level under equivalent conditions."
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"Recent in vitro studies have indicated that probucol reduces hERG expression in the plasma membrane and does not directly block human ether-a-go-go-related gene (hERG) channels."
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"Our data are consistent with the report that probucol, also a cholesterol lowering drug, decreases hERG expression through accelerating cav-1 degradation."
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"In the present study, we confirmed that Nedd4-2 is involved in the process of probucol disrupted hERG surface expression."
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"In summary, the present study provides evidence that probucol does not block the hERG channel, but accelerates degradation of the mature hERG channel and inhibit hERG current by decreasing SGK1 expression level and eventually enhancing the ubiquitination of the hERG channel through the E3 ubiquitin ligase Nedd4-2, whereas CCh can rescue probucol disrupted hERG surface expression by enhancing the phosphorylation level of Nedd4-2 as an alternative to SGK1."
26229434
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"The study showed that probucol may induce QTc interval prolongation through decreasing the plasma-membrane hERG protein expression (57), as the decline of hERG channel is assumed to be a likely mechanism for the prolongation of QTc interval (44, 47)."
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"Although probucol is reported to reduce hERG expression in the plasma membrane without directly blocking hERG channel (Shi et al., 2015) and to prolong QT and cause TdPs in patients and in animal studies (Nogawa et al., 2013), the prolongation of the QT interval is not as evident as after treatment with other drugs, such as from arsenic trioxide and/or pentamidine."
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"Thus, probucol reduces hERG expression through accelerating Cav1 turnover."
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"cardiac glycosides, arsenic trioxide, pentamidine, probucol and ketoconazole) ( Wang et al., 2007; Ficker et al., 2004; Kuryshev et al., 2005; Guo et al., 2007; Takemasa et al., 2008 ) reduce hERG sur[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
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