| First Author | Chen Z | Year | 2022 |
| Journal | Free Radic Biol Med | Volume | 194 |
| Pages | 62-70 | PubMed ID | 36410585 |
| Mgi Jnum | J:331933 | Mgi Id | MGI:7407852 |
| Doi | 10.1016/j.freeradbiomed.2022.11.030 | Citation | Chen Z, et al. (2022) Critical role of caveolin-1 in intestinal ischemia reperfusion by inhibiting protein kinase C betaII. Free Radic Biol Med 194:62-70 |
| abstractText | Intestinal ischemia reperfusion (I/R) is a common clinical pathological process. We previously reported that pharmacological inhibition of protein kinase C (PKC) betaII with a specific inhibitor attenuated gut I/R injury. However, the endogenous regulatory mechanism of PKCbetaII inactivation is still unclear. Here, we explored the critical role of caveolin-1 (Cav1) in protecting against intestinal I/R injury by regulating PKCbetaII inactivation. PKCbetaII 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 PKCbetaII activation and increased oxidative stress and apoptosis after intestinal I/R. Full-length Cav1 scaffolding domain peptide (CSP) suppressed excessive PKCbetaII activation and protected the gut against oxidative stress and apoptosis due to I/R injury. In summary, Cav1 could regulate PKCbetaII 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. |
