Catestatin (CST) is a catecholamine release-inhibitory peptide secreted from the adrenergic neurons and the adrenal glands. It regulates the cardiovascular functions and it is associated with cardiovascular diseases. Though its mechanisms of actions are not known, there are evidences of cross-talk between the adrenergic and CST signaling. We hypothesized that CST moderates the adrenergic overdrive and studied its effects on norepinephrine-mediated hypertrophic responses in H9c2 cardiac myoblasts. CST alone regulated the expression of a number of fetal genes that are induced during hypertrophy. When cells were pre-treated CST, it blunted the modulation of those genes by norepinephrine. Norepinephrine (2 µM) treatment also increased cell size and enhanced the level of Troponin T in the sarcomere. These effects were attenuated by the treatment with CST. CST attenuated the immediate generation of ROS and the increase in glutathione peroxidase activity induced by norepinephrine treatment. Expression of fosB and AP-1 promoter-reporter constructs was used as the endpoint readout for the interaction between the CST and adrenergic signals at the gene level. It showed that CST largely attenuates the stimulatory effects of norepinephrine and other mitogenic signals through the modulation of the gene regulatory modules in a characteristic manner. Depending upon the dose, the signaling by CST appears to be disparate, and at 10-25 nM doses, it primarily moderated the signaling by the β1/2-adrenoceptors. This study, for the first time, provides insights into the modulation of adrenergic signaling in the heart by CST.

中文翻译：

---

Catestatin通过调节肾上腺素能信号转导去甲肾上腺素对H9c2心肌成肌细胞的肥大作用。

Catestatin（CST）是一种从肾上腺素能神经元和肾上腺分泌的儿茶酚胺释放抑制肽。它调节心血管功能，并与心血管疾病有关。尽管其作用机理尚不清楚，但有证据表明肾上腺素能和CST信号传导之间存在串扰。我们假设CST可以减轻肾上腺素的过度驱动，并研究其对去甲肾上腺素介导的H9c2心肌成肌细胞肥大反应的影响。单独的CST调节肥大过程中诱导的许多胎儿基因的表达。当细胞经过预处理的CST时，它会减弱去甲肾上腺素对那些基因的调节作用。去甲肾上腺素（2 µM）处理还增加了细胞大小，并增强了肌小节中肌钙蛋白T的水平。通过CST的治疗减弱了这些作用。CST减弱了去甲肾上腺素治疗诱导的ROS的立即生成和谷胱甘肽过氧化物酶活性的增加。fosB和AP-1启动子-报告子构建体的表达被用作在基因水平上CST和肾上腺素能信号之间相互作用的终点读数。结果表明，CST通过以特定方式调节基因调节模块，大大减弱了去甲肾上腺素和其他有丝分裂信号的刺激作用。取决于剂量，CST的信号传导似乎是完全不同的，并且在10-25 nM剂量下，它主要通过β1/ 2-肾上腺素能受体缓和了信号传导。这项研究首次提供了有关CST调节心脏中肾上腺素信号传导的见解。CST减弱了去甲肾上腺素治疗诱导的ROS的立即生成和谷胱甘肽过氧化物酶活性的增加。fosB和AP-1启动子-报告子构建体的表达被用作在基因水平上CST和肾上腺素能信号之间相互作用的终点读数。结果表明，CST通过以特定方式调节基因调节模块，大大减弱了去甲肾上腺素和其他有丝分裂信号的刺激作用。取决于剂量，CST的信号传导似乎是完全不同的，并且在10-25 nM剂量下，它主要通过β1/ 2-肾上腺素能受体缓和了信号传导。这项研究首次提供了有关CST调节心脏中肾上腺素信号传导的见解。CST减弱了去甲肾上腺素治疗诱导的ROS的立即生成和谷胱甘肽过氧化物酶活性的增加。fosB和AP-1启动子-报告子构建体的表达被用作在基因水平上CST和肾上腺素能信号之间相互作用的终点读数。结果表明，CST通过以特定方式调节基因调节模块，大大减弱了去甲肾上腺素和其他有丝分裂信号的刺激作用。取决于剂量，CST的信号传导似乎是完全不同的，并且在10-25 nM剂量下，它主要通过β1/ 2-肾上腺素能受体缓和了信号传导。这项研究首次提供了有关CST调节心脏中肾上腺素信号传导的见解。