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- W2092808306 abstract "We have previously shown increased cardiac stanniocalcin-1 (STC1) in patients with idiopathic dilated cardiomyopathy. STC1 localizes to the inner mitochondrial membrane and transgenic over-expression of STC1 is associated with increased energy utilization.We examined the hypothesis that STC1 uncouples mitochondrial oxidative phosphorylation--to suppress superoxide generation and modulate neurohormonal effects on cardiomyocytes.Compared to WT mouse heart, STC1 Tg heart displays: 2-fold higher uncoupling protein 3 (UCP3) levels, but no effect on UCP2 protein; 40% lower ATP levels; but similar activities of respiratory chain complexes I-IV. In cultured adult rat and freshly-isolated mouse cardiomyocytes, rSTC1 induces UCP3, but not UCP2. Treatment of cardiomyocytes with STC1 decreases mitochondrial membrane potential and suppresses baseline and angiotensin II (Ang II)-induced superoxide generation. Furthermore, baseline superoxide generation is higher in freshly-isolated adult UCP3(-/-) mouse cardiomyocytes compared to WT, suggesting an important role for UCP3 in regulating cardiomyocyte ROS under physiologic conditions. Treatment of UCP3(-/-) cardiomyocytes with rSTC1 failed to suppress superoxide generation, suggesting that the effects of STC1 on superoxide generation in cardiomyocytes are UCP3-dependent.STC1 activates a novel anti-oxidant pathway in cardiac myocytes through induction of UCP3, and may play an important role in suppressing ROS in the heart under normal physiologic conditions and ameliorate the deleterious effects of Ang II-mediated cardiac injury. Importantly, our data point to a critical role for the mitochondria in regulating ROS generation in response to Ang II." @default.
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- W2092808306 date "2012-05-31" @default.
- W2092808306 modified "2023-09-24" @default.
- W2092808306 title "Human Stanniocalcin-1 Suppresses Angiotensin II-Induced Superoxide Generation in Cardiomyocytes through UCP3-Mediated Anti-Oxidant Pathway" @default.
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- W2092808306 doi "https://doi.org/10.1371/journal.pone.0036994" @default.
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