Intestinal ischemia reperfusion (I/R) is a common clinical pathological process. We previously reported that pharmacological inhibition of protein kinase C (PKC) βII with a specific inhibitor attenuated gut I/R injury. However, the endogenous regulatory mechanism of PKCβII inactivation is still unclear. Here, we explored the critical role of caveolin-1 (Cav1) in protecting against intestinal I/R injury by regulating PKCβII inactivation. PKCβII translocated to caveolae and bound with Cav1 after intestinal I/R. Cav1 was highly expressed in the intestine of mice with I/R and IEC-6 cells stimulated with hypoxia/reoxygenation (H/R). Cav1-knockout (KO) mice suffered from worse intestinal injury after I/R than wild-type (WT) mice and showed extremely low survival due to exacerbated systemic inflammatory response syndrome (SIRS) and remote organ (lung and liver) injury. Cav1 deficiency resulted in excessive PKCβII activation and increased oxidative stress and apoptosis after intestinal I/R. Full-length Cav1 scaffolding domain peptide (CSP) suppressed excessive PKCβII activation and protected the gut against oxidative stress and apoptosis due to I/R injury. In summary, Cav1 could regulate PKCβII endogenous inactivation to alleviate intestinal I/R injury. This finding may represent a novel therapeutic strategy for the prevention and treatment of intestinal I/R injury.
Keywords: Cav1; Cav1 scaffolding domain peptide; Intestinal ischemia reperfusion; Oxidative stress; PKCβII.
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