Tumorous Imaginal Disc 1 (Tid1) Inhibits Isoproterenol-Induced Cardiac Hypertrophy And Apoptosis By Regulating C-Terminus Of Hsc70-Interacting Protein (Chip) Mediated Degradation Of G Alpha S

Dilated cardiomyopathy (DCM) is the most common form of non-ischemic cardiomyopathy. It is characterized by ventricular chamber dilation, and myocyte hypertrophy. Human tumorous imaginal disc 1 (Tid 1 ), a chaperone protein and response to regulate number of signaling molecules in the mitochondria or cytosol. Tid 1 also plays a major role in preventing DCM; however, the role of Tid1 in isoproterenol (ISO)-induced cardiac apoptosis and hypertrophy remains unclear. H9c2 cells were pretreated Tid 1 before ISO-induced hypertrophy and apoptosis and then evaluated by IHC, TUNEL assay, IFC, Co-IP, and Western blot. From the IHC experiment, we found that Tid1 proteins were increased in tissues from different stages of human myocardial infarction. Using H9c2 cardiomyoblast cells we found that Tid 1 was decreased by ISO treatment. However, over-expression of Tid1S suppressed NFATc3, BNP and calcineurin protein expression and inhibited NFATc3 nuclear translocation in ISO induced cardiomyoblast cells. On the other hand, Tid 1 S over-expression activated survival proteins p-AKT(ser473) and decreased caspase-3 and cytochrome c expression. We also found that overexpression of Tid 1 enhanced CHIP expression, and induced CHIP to ubiquitinate G alpha s, resulting in increased G alpha s degradation. Our study showed that G alpha s is a novel substrate of CHIP, and we also found that the lid 1 -CHIP complex plays an essential role in inhibiting ISO induced cardiomyoblast hypertrophy and apoptosis.