Role of a new-type polypeptide in regulation of oxidative stress in cardiac hypertrophy through ox-CaMK Ⅱ

作者：ZHENG Xi; LI Jing-yuan; WANG Si-qi; ZHANG Chen-yang; HU Cong; TONG Xin; TIAN Xing; GU Li-xian; CHANG Xin-yi; HAO Li-ying

来源：中国药理学与毒理学杂志, 2019, 33(10): 806-807.

OBJECTIVE Oxidative stress is the imbalance between the production and removal of reactive oxygen species(ROS), leading to cel and tissue damage.There is growing evidence that excessive ROS is induced in cardiac hypertrophy and heart failure. Over accumulation of ROS subsequently activates ROS-sensitive downstream signaling pathways associated with pathological myocardial hypertrophy. Angiotensin Ⅱ(Ang Ⅱ)increases ROS in ventricular myocardium by acting on oxidized CaMK Ⅱ(ox-CaMK Ⅱ). This study will explore the role of a new polypeptide targeting on CaMKⅡ in the regulation of oxidative stress in cardiac hypertrophy through ox-CaMKⅡ, and provide a new target and a new way for the treatment of cardiac hypertrophy. METHODS H9c2 cells were divided into three groups. The control group was given complete medium. The cardiac hypertrophy group was administered by 100 nmol·L-1 AngⅡ. After 24 h of administration of Ang Ⅱ, the polypeptide group was given a new type polypeptide, 5 μg· m L-1. Oxidative stress was estimated in vivo by measuring ROS level,ox-CaMK Ⅱ expression and superoxide dismutase(SOD)activity. RESULTS Compared with that of the control group, the SOD activity in the cardiac hypertrophy group was decreased, while the new polypeptide could significantly improve the SOD activity. Among the three groups, the expression of ox-CaMK Ⅱ in the cardiac hypertrophy group was the highest, demonstrating that this novel polypeptide could reduce ox-CaMKⅡ expression. CONCLUSION In conclusion, our newly designed CaMKⅡ-targeted polypeptide can inhibit ROS-mediated downstream pathway by inhibiting ox-CaMK Ⅱ expression and reducing excessive ROS accumulation, thereby reversing cardiac hypertrophy.