GLP-1(7-36), a major active form of GLP-1 hormone, is rapidly cleaved by dipeptidyl peptidase-4 to generate a truncated metabolite, GLP-1(9-36) which has a low affinity for GLP-1 receptor (GLP-1R). GLP-1(7-36) has been shown to have protective effects on cardiovascular system through GLP-1R-dependent pathway. Nevertheless, the cardioprotective effects of GLP-1(9-36) have not fully understood. The present study investigated the effects of GLP-1(9-36), including its underlying mechanisms against oxidative stress and apoptosis in H9c2 cells. Here, we reported that GLP-1(9-36) protects H9c2 cardiomyoblasts from hydrogen peroxide (H2O2)-induced oxidative stress by promoting the synthesis of antioxidant enzymes, glutathione peroxidase-1, catalase, and heme oxygenase-1. In addition, treatment with GLP-1(9-36) suppressed H2O2-induced apoptosis by attenuating caspase-3 activity and upregulating proapoptotic proteins, Bcl-2 and Bcl-xL. These protective effects of GLP-1(9-36) are attenuated by blockade of PI3K-mediated Akt phosphorylation and prevention of nitric oxide synthase (NOS)-induced nitric oxide production. Thus, GLP-1(9-36) represents the potential therapeutic target for prevention of oxidative stress and apoptosis in the heart via PI3K/Akt/NOS signaling pathway.

中文翻译：

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GLP-1(9-36) 对 H9c2 心肌细胞氧化损伤的心脏保护作用：PI3K/Akt/NOS 途径的潜在作用。


GLP-1(7-36) 是 GLP-1 激素的主要活性形式，可被二肽基肽酶 4 快速裂解，生成截短的代谢物 GLP-1(9-36)，其与 GLP-1 的亲和力较低受体（GLP-1R）。 GLP-1(7-36) 已被证明通过 GLP-1R 依赖性途径对心血管系统具有保护作用。然而，GLP-1(9-36) 的心脏保护作用尚未完全了解。本研究调查了 GLP-1(9-36) 的作用，包括其对抗 H9c2 细胞氧化应激和凋亡的潜在机制。在此，我们报道GLP-1(9-36)通过促进抗氧化酶、谷胱甘肽过氧化物酶-1、过氧化氢酶和血红素加氧酶-1的合成来保护H9c2心肌细胞免受过氧化氢(H2O2)诱导的氧化应激。此外，GLP-1(9-36) 治疗可通过减弱 caspase-3 活性并上调促凋亡蛋白 Bcl-2 和 Bcl-xL 来抑制 H2O2 诱导的细胞凋亡。 GLP-1(9-36) 的这些保护作用会通过阻断 PI3K 介导的 Akt 磷酸化和阻止一氧化氮合酶 (NOS) 诱导的一氧化氮产生而减弱。因此，GLP-1(9-36)代表了通过PI3K/Akt/NOS信号通路预防心脏氧化应激和细胞凋亡的潜在治疗靶点。