Critical role of caveolin-1 in intestinal ischemia reperfusion by inhibiting protein kinase C ßII.
Free Radic Biol Med
; 194: 62-70, 2023 01.
Article
em En
| MEDLINE
| ID: mdl-36410585
ABSTRACT
Intestinal ischemia reperfusion (I/R) is a common clinical pathological process. We previously reported that pharmacological inhibition of protein kinase C (PKC) ßII with a specific inhibitor attenuated gut I/R injury. However, the endogenous regulatory mechanism of PKCßII inactivation is still unclear. Here, we explored the critical role of caveolin-1 (Cav1) in protecting against intestinal I/R injury by regulating PKCßII inactivation. PKCßII 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 PKCßII activation and increased oxidative stress and apoptosis after intestinal I/R. Full-length Cav1 scaffolding domain peptide (CSP) suppressed excessive PKCßII activation and protected the gut against oxidative stress and apoptosis due to I/R injury. In summary, Cav1 could regulate PKCßII 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.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Contexto em Saúde:
6_ODS3_enfermedades_notrasmisibles
Base de dados:
MEDLINE
Assunto principal:
Traumatismo por Reperfusão
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Caveolina 1
Limite:
Animals
Idioma:
En
Revista:
Free Radic Biol Med
Ano de publicação:
2023
Tipo de documento:
Article