Zhang Nan, Ji Na, Jiang Wei-Ming, Li Zhong-Yi, Wang Ming, Wen Jia-Ming, Li Yi, Chen Xin, Chen Ji-Min
Department of Urology, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
Department of Anesthesia, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
Biochem Biophys Res Commun. 2015 Sep 4;464(4):1107-1112. doi: 10.1016/j.bbrc.2015.07.086. Epub 2015 Jul 23.
Benign prostatic hyperplasia (BPH) is emerging as one of the most common diseases seriously threatening the health of elderly men. Accumulating evidences indicate that hypoxia could induce BPH. However, the underlying mechanism of BPH induced by hypoxia is not clear. In the study, hypoxia-induced autophagy could promote cell survival and endoplasmic reticula stress (ER stress) in WPMY-1 cells. Cell viability induced by hypoxia could been decreased by autophagy inhibitors (3-methyladenine, bafilomycin A1) or siRNA interference in two autophagy genes (Beclin1, ATG5) in WPMY-1 cells. Furthermore, ER stress was present in hypoxia-treated WPMY-1 cells, while autophagy and cell survival could been inhibited by C/EBP-homologous protein siRNA (CHOP), which is an important protein of ER stress pathway. Taken together, our data support a novel model that autophagy as a cytoprotective response promotes cell survival via ER stress under hypoxia in human prostate stromal cells.
良性前列腺增生（BPH）正逐渐成为严重威胁老年男性健康的最常见疾病之一。越来越多的证据表明，缺氧可诱发BPH。然而，缺氧诱导BPH的潜在机制尚不清楚。在本研究中，缺氧诱导的自噬可促进WPMY-1细胞的存活和内质网应激（ER应激）。在WPMY-1细胞中，自噬抑制剂（3-甲基腺嘌呤、巴弗洛霉素A1）或对两个自噬基因（Beclin1、ATG5）的siRNA干扰可降低缺氧诱导的细胞活力。此外，缺氧处理的WPMY-1细胞中存在ER应激，而作为ER应激途径重要蛋白的C/EBP同源蛋白siRNA（CHOP）可抑制自噬和细胞存活。综上所述，我们的数据支持一种新模型，即在人前列腺基质细胞缺氧条件下，自噬作为一种细胞保护反应通过ER应激促进细胞存活。
