Propofol Provides Cardiac Protection by Suppressing the Proteasome Degradation of Caveolin-3 in Ischemic/Reperfused Rat Hearts

Afang Zhu, Xin Wei, Yali Zhang, Tao You, Shanglong Yao, Shiying Yuan, Haodong Xu, Faqian Li, Weike Mao

Research output: Contribution to journalArticlepeer-review

12 Scopus citations

Abstract

The mechanisms underlying propofol's cardioprotective role remain elusive. Caveolin-3 (Cav-3) has been shown to mediate both opioids-and volatile anesthetics-induced cardioprotection against ischemia/reperfusion (I/R) injury. We hypothesize that the cardioprotective role of propofol is mediated through Cav-3 and its regulation of PI3K/Akt/GSK3β signal pathway. Rats or H9c2 cardiomyocytes were exposed to propofol before I/R or simulated ischemia/reperfusion (SI/R). Propofol pretreatment significantly decreased left ventricle infarct size in vivo (P < 0.05) and terminal deoxynucleotidyl transferase nick-end labeling-positive cells both in vivo and in vitro (P < 0.05), along with an increased Cav-3 protein expression and binding of Cav-3 to p85-subunit of PI3K. No significant change in Cav-3 mRNA expression in left ventricle tissues was found in either I/R or propofol-treated groups. Methyl-β-cyclodextrin or Cav-3 siRNA was used to knockdown Cav-3 expression in vitro, which virtually abolished propofol-induced cardiac protection and PI3K/Akt/GSK3β pathway activation. In contrast, MG132, a proteasome inhibitor, could significantly restore SI/R-induced Cav-3 decrease. It is concluded that Cav-3 mediates propofol-induced cardioprotection against I/R injury and the relevant PI3K/Akt/GSK3β activation. The downregulation of Cav-3 under SI/R may be caused by proteasome degradation, and this process can be prevented by propofol.

Original languageEnglish (US)
Pages (from-to)170-177
Number of pages8
JournalJournal of Cardiovascular Pharmacology
Volume69
Issue number3
DOIs
StatePublished - Mar 1 2017

Bibliographical note

Publisher Copyright:
© 2016 Wolters Kluwer Health, Inc.

Keywords

  • Degradation
  • PI3K/Akt/GSK3β
  • caveolin-3
  • ischemia/reperfusion
  • propofol

Fingerprint

Dive into the research topics of 'Propofol Provides Cardiac Protection by Suppressing the Proteasome Degradation of Caveolin-3 in Ischemic/Reperfused Rat Hearts'. Together they form a unique fingerprint.

Cite this