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 (Tid1), a chaperone protein and response to regulate number of signaling molecules in the mitochondria or cytosol. Tid1 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 Tid1 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 Tid1 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, Tid1S over-expression activated survival proteins p-AKTser473 and decreased caspase-3 and cytochrome c expression. We also found that overexpression of Tid1 enhanced CHIP expression, and induced CHIP to ubiquitinate Gαs, resulting in increased Gαs degradation. Our study showed that Gαs is a novel substrate of CHIP, and we also found that the Tid1-CHIP complex plays an essential role in inhibiting ISO induced cardiomyoblast hypertrophy and apoptosis.
This study investigates the cardio-protective effect of Nos. 1 and 5 extracts from Taiwan Mingjian Oolong Tea on H9c2 cardiomyoblast cells treated with isoproterenol (ISO). Treatment with Nos. 1 and 5 extracts increased cell viability and blocked apoptosis in ISO exposed H9c2 cells. Moreover, Nos. 1 and 5 extracts blocked hypertrophy markers like G[Formula: see text]s, calcineurin, NFATc3, and BNP, thereby increasing cell proliferation markers -PI3K and AKT in a dose dependent manner. In contrast, apoptotic proteins, such as caspase-3 and cytochrome c were decreased in H9c2 cells treated with Nos. 1 and 5 extracts. We confirmed that the protective effect of No. 1 extract was partially mediated through the expression of ERK and p38, however, the No. 5 extract showed a protective effect via the ERK, JNK, and p38 pathways. This evidence provides new insights into the pharmacological role and therapeutic mechanism of Taiwan Mingjian Oolong Tea in heart diseases.
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