Fluvastatin inhibits Rab5-mediated IKs internalization caused by chronic Ca²⁺-dependent PKC activation.

ABSTRACT: Statins, in addition to their cholesterol lowering effects, can prevent isoprenylation of Rab GTPase proteins, a key protein family for the regulation of protein trafficking. Rab-GTPases have been shown to be involved in the control of membrane expression level of ion channels, including one of the major cardiac repolarizing channels, IKs. Decreased IKs function has been observed in a number of disease states and associated with increased propensity for arrhythmias, but the mechanism underlying IKs decrease remains elusive. Ca²⁺-dependent PKC isoforms (cPKC) are chronically activated in variety of human diseases and have been suggested to acutely regulate IKs function. We hypothesize that chronic cPKC stimulation leads to Rab-mediated decrease in IKs membrane expression, and tha

SUBMITTER: Parks XX 

PROVIDER: S-EPMC6645917 | biostudies-literature | 2019 Apr

REPOSITORIES: biostudies-literature