Endotoxemia Engages the XXXX Kinase Pathway to Impair Cardiac Function By Altering Cytoskeleton, Mitochondrial Fission, and Autophagy.

@entity1 @entity32 @entity8232 @entity5694 @entity558 @entity12386 @entity296 @entity295 @entity19 @entity25490 @entity3547 @entity299 @entity2383
AIMS: The @entity3547 /ROCK pathway controls crucial biological processes involved in cardiovascular pathophysiology, such as cytoskeleton dynamics, vascular smooth muscle contraction, and @entity32 . In this work, we tested whether Rho kinase inhibition would beneficially impact cardiac cytoskeleton organization, bioenergetics, and autophagy in experimental @entity5694 induced by lipopolysaccharides (LPSs) in @entity19 . RESULTS: @entity8232 , a potent ROCK inhibitor, prevented @entity558 -induced @entity299 , oxidative stress, cytoskeleton disarray, and @entity2383 . ROCK inhibition prevented phosphorylation of @entity12386 and @entity25490 , which promotes stabilization-polymerization of F-actin and mediates mitochondrial fission, respectively. Pyr1, which exclusively alters actin dynamics, prevented @entity558 -induced @entity296 , suggesting that beneficial impact of ROCK inhibition was not mainly related to pleiotropic effects of @entity8232 on @entity299 and oxidative stress. @entity8232 reduced mitochondrial fragmentation, stimulated initiation of autophagy, and elicited cardioprotection in @entity558 heart. Mdivi-1, a potent mitochondria fission inhibitor, converted cardioprotective autophagy to an inefficient form due to cargo loading failure in which autophagic vacuoles fail to trap cytosolic cargo, despite their formation at enhanced rates and lysosomal elimination. INNOVATION: In experimental @entity5694 , cardioprotection by @entity3547 /ROCK inhibition may be related to changes in actin cytoskeleton reorganization and mitochondrial homeostasis. Improvement of @entity558 -induced @entity2383 by @entity8232 was attributed to inhibition of ROCK-dependent @entity25490 phosphorylation and activation of autophagic processes that can limit mitochondrial fragmentation and enhance degradation of damaged mitochondria, respectively. CONCLUSION: @entity8232 prevented @entity558 -induced heart oxidative stress, abnormal F-actin distribution, and oxidative phosphorylation, which concur to improve cardiac contractile and bioenergetic function. We suggest that @entity8232 may represent a valuable therapy for @entity1 with @entity295 . Antioxid. Redox Signal. 00, 000-000.
