Institute of Cardiovascular Diseases, Jiangxi Academy of Clinical Medical Sciences, the First Affiliated Hospital of Nanchang University, Nanchang 330006, China.
Department of rehabilitation, the First Affiliated Hospital of Nanchang University, Nanchang 330006, China.
Biomed Pharmacother. 2022 Sep;153:113403. doi: 10.1016/j.biopha.2022.113403. Epub 2022 Jul 13.
Doxorubicin (Dox)-induced cardiotoxicity (DIC) seriously threatens the health of related patients. Studies have confirmed that 14-3-3γ and protein kinase C epsilon (PKCε) are the endogenous protective proteins. Puerarin (Pue) is a bioactive ingredient isolated from the root of Pueraria lobata. It possesses many pharmacological properties, which have been widely used in treating and adjuvant therapy of cardiovascular diseases. In the study, we intended to explore the effects and mechanism of Pue pretreatment to protect the myocardium against DIC injury. Adult mice and H9c2 cells were pretreated with Pue, and the injury model was made with Dox. Results showed that Pue pretreatment alleviated DIC injury, as revealed by increased cell viability, decreased LDH activity and apoptosis, inhibited excess oxidative stress, maintained mitochondrial function and energy metabolism, and improved myocardial function. Furthermore, Pue pretreatment upregulated 14-3-3γ expression, interacted with PKCε, phosphorylated and impelled migration to mitochondria, activated adaptive autophagy, and protected the myocardium. However, pAD/14-3-3γ-shRNA or εV1-2 (a PKCε activity inhibitor) or 3-methyladenine (an autophagy inhibitor) could weaken the above effects of Pue pretreatment. Together, Pue pretreatment could activate adaptive autophagy by the 14-3-3γ/PKCε pathway and protect the myocardium against DIC injury.
阿霉素（Dox）诱导的心脏毒性（DIC）严重威胁相关患者的健康。研究已证实，14-3-3γ和蛋白激酶 C ɛ（PKCε）是内源性保护蛋白。葛根素（Pue）是从野葛根中分离得到的一种生物活性成分。它具有许多药理作用，已广泛用于治疗和辅助治疗心血管疾病。在这项研究中，我们旨在探讨葛根素预处理对保护心肌免受 DIC 损伤的作用及其机制。用葛根素预处理成年小鼠和 H9c2 细胞，并使用阿霉素制作损伤模型。结果表明，葛根素预处理可通过增加细胞活力、降低 LDH 活性和凋亡、抑制过度氧化应激、维持线粒体功能和能量代谢、改善心肌功能来缓解 DIC 损伤。此外，葛根素预处理可上调 14-3-3γ 的表达，与 PKCε 相互作用，磷酸化并促使其向线粒体迁移，激活适应性自噬，从而保护心肌。然而，pAD/14-3-3γ-shRNA 或 εV1-2（PKCε 活性抑制剂）或 3-甲基腺嘌呤（自噬抑制剂）可削弱葛根素预处理的上述作用。综上所述，葛根素预处理可通过 14-3-3γ/PKCε 通路激活适应性自噬，从而保护心肌免受 DIC 损伤。
