Department of Urology, Zhongshan Hospital, Fudan University, Shanghai 200032, P R China.
Exp Biol Med (Maywood). 2013 Jan;238(1):111-9. doi: 10.1258/ebm.2012.012185.
Erythropoietin (EPO) has been well recognized as a tissue protective agent by inhibiting apoptosis and inflammation. The tissue protective effect of EPO, however, only occurs at a high dosage, which may elicit severe side-effects at the meantime. Helix B surface peptide (HBSP), a novel peptide derived from the non-erythropoietic helix B of EPO, plays a specific role in tissue protection. We investigated effects of HBSP and the expression of its heterodimeric receptor, beta common receptor (βcR)/EPO receptor ( ), in a murine renal ischemia reperfusion (IR) injury model. HBSP significantly ameliorated renal dysfunction and tissue damage, decreased apoptotic cells in the kidney and reduced activation of caspase-9 and -3. The βcR/EPOR in the kidney was up-regulated by IR, but down-regulated by HBSP. Further investigation revealed that the expression and phosphorylation of Akt was dramatically enhanced by HBSP, but strongly reversed by wortmannin, the PI3K inhibitor. Wortmannin intervention improved βcR/EPOR expression, promoted caspase-9 and -3 activation, and increased active caspase-3 positive cells, while renal function and structure, and apoptotic cell counts scarcely changed. This result indicates a significant contribution of PI3K/Akt signaling pathway in the renoprotection of HBSP. The therapeutic effects of HBSP in this study suggest that HBSP could be a better candidate for renal protection.
促红细胞生成素（EPO）通过抑制细胞凋亡和炎症反应而被广泛认为是一种组织保护剂。然而，EPO 的组织保护作用仅在高剂量时才会发生，同时可能会引起严重的副作用。螺旋 B 表面肽（HBSP）是一种源自 EPO 的非促红细胞生成螺旋 B 的新型肽，在组织保护中发挥特定作用。我们在小鼠肾缺血再灌注（IR）损伤模型中研究了 HBSP 及其异二聚体受体β共同受体（βcR）/EPO 受体（）的表达的作用。HBSP 显著改善了肾功能和组织损伤，减少了肾脏中的凋亡细胞，并降低了 caspase-9 和 -3 的活性。IR 上调了肾脏中的βcR/EPOR，但 HBSP 下调了其表达。进一步的研究表明，HBSP 显著增强了 Akt 的表达和磷酸化，而 PI3K 抑制剂wortmannin 则强烈逆转了这一作用。wortmannin 干预增强了βcR/EPOR 的表达，促进了 caspase-9 和 -3 的激活，并增加了活性 caspase-3 阳性细胞，而肾功能和结构以及凋亡细胞计数几乎没有变化。这一结果表明，PI3K/Akt 信号通路在 HBSP 的肾脏保护中具有重要作用。HBSP 在本研究中的治疗效果表明，HBSP 可能是一种更好的肾脏保护候选药物。
