The effect of transforming growth factor β1 on the crosstalk between autophagy and apoptosis in the annulus fibrosus cells under serum deprivation

被引：99

作者：

Ni, Bin-Bin ^{[1
]}

Li, Bo ^{[1
]}

Yang, Yue-Hua ^{[1
]}

Chen, Jiang-Wei ^{[1
]}

Chen, Ke ^{[1
]}

Jiang, Sheng-Dan ^{[1
]}

Jiang, Lei-Sheng ^{[1
]}

机构：

[1] Shanghai Jiao Tong Univ, Sch Med, Xinhua Hosp, Dept Orthoped Surg, Shanghai 200092, Peoples R China

来源：

CYTOKINE | 2014年 / 70卷 / 02期

基金：

中国国家自然科学基金;

关键词：

TGF-beta; 1; Autophagy; Apoptosis; Serum deprivation; Disc degeneration; HUMAN INTERVERTEBRAL DISC; LOW-BACK-PAIN; TGF-BETA; OXIDATIVE STRESS; NUCLEUS PULPOSUS; CANCER CELLS; DEATH; MACROAUTOPHAGY; EXPRESSION; RECEPTOR;

D O I：

10.1016/j.cyto.2014.07.249

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

070307 [化学生物学]; 071010 [生物化学与分子生物学];

摘要：

Autophagy and apoptosis are important in maintaining the metabolic homeostasis of intervertebral disc cells, and transforming growth factor-beta 1 (TGF-beta 1) is able to delay intervertebral disc degeneration. This study determined the effect of TGF-beta 1 on the crosstalk between autophagy and apoptosis in the disc cells, with the aim to provide molecular mechanism support for the prevention and treatment of disc degeneration. Annulus fibrosus (AF) cells were isolated and cultured under serum starvation. 10 ng/mL TGF-beta 1 reduced the apoptosis incidence in the cells under serum starvation for 48 h, down-regulated the autophagy incidence in the cells pretreated with 3-methyladenine (3-MA) or Bafilomycin A (Baf A), partly rescued the increased apoptosis incidence in the cells pretreated with 3-MA, while further reduced the decreased apoptosis incidence in the cells pretreated with Baf A. Meanwhile, TGF-beta 1 down-regulated the expressions of autophagic and apoptotic markers in the cells under starvation, partly down-regulated the expressions of Beclin-1, LC3 II/I and cleaved caspase-3 in the cells pretreated with 3-MA or Baf A, while significantly decreased the expression of Bax/Bcl-2 in the cells pretreated with Baf A. 3-MA blocked the phosphorylation of both ART and mTOR and partly reduced the inhibitory effect of TGF-beta 1 on the expression of LC3 II/I and cleaved caspase-3. TGF-beta 1 enhanced the expression of p-ERK1/2 and down-regulated the expressions of LC3 II/I and cleaved caspase-3. U0126 partly reversed this inhibitory effect of TGF-beta 1. In conclusion, TGF-beta 1 protected against apoptosis of AF cells under starvation through down-regulating excessive autophagy. PI3K-AKT-mTOR and MAPK-ERK1/2 were the possible signaling pathways involved in this process. (C) 2014 Elsevier Ltd. All rights reserved.

引用

页码：87 / 96

页数：10

共 72 条

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