Bag-1 modulates lung ischemia-reperfusion injury by regulating BCL-2 family proteins and IP3R-mediated calcium release

Lung ischemia-reperfusion injury (LIRI) involves dysregulated apoptosis and calcium overload. This study explored the role of molecular chaperone BCL-2-associated athanogene 1 (Bag-1) -1 in LIRI pathogenesis. Using an A549 cell model of glucose deprivation/hypoxia-reoxygenation, Bag-1 was silenced via SiRNA, and the IP3R inhibitor Xestospongin C (XSC) was applied. Bag-1 knockdown downregulated anti-apoptotic BCL-xL, and MCL-1, while upregulating cleaved Caspase-3, and phosphorylated IP3R, inducing calcium overload and impairing ATPase activities. Co-treatment with XSC reversed these effects, restoring anti-apoptotic protein levels, reducing apoptosis, normalizing calcium, and improving ATPase function. This study identifies Bag-1 modulates LIRI by regulating BCL-2 family and IP3R-mediated calcium release, however the proposed sequential pathway remains correlative rather than causative, Time-series intervention and rescue experiments are warranted to definitively establish the directionality of these molecular events.