Issue Archive

The relationships among reactive oxygen species, hypoxia--inducible factor 1#alpha# and cell proliferation in rat pulmonary arterial smooth muscle cells under hypoxia

Zhao Jianping, Zhou Zhigang, Hu Hongling, Guo Zhi, Wang Tao, Zhen Guohua, Zhang Zhenxiang

Department of Respiratory Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology.Wuhan 430030,Hubei

Abstract

The objectives of this paper were to observe the changes of reactive oxygen species （ROS） in rat pulmonary arterial smooth muscle cells （PASMCs） under hypoxic condition and to test if hypoxia-induced proliferation of PASMCs was mediated by ROS. PASMCs were divided into three groups： normal group, hypoxia group and hypoxia + Mn-TBAP （a ROS scavenger） group. The level of ROS was determined by a laser scanning confocal microscope. The expression of hypoxia-inducible factor 1#alpha#（HIF-1#alpha#） mRNA was detected by semi-quantitative reverse transcription PCR （RT-PCR）. HIF-1#alpha# protein was detected using immunohistochemical staining, and the proliferation of PASMCs was examined by MTT colorimetric assay. The results were as follows： （1） The level of ROS in hypoxia group was significantly increased as compared with that in the normal group （P〈0.05）. The level of ROS in hypoxia + Mn-TBAP group was significantly decreased as compared with that in hypoxia group （P〈0.05）, but was increased as compared with that in the normal group （P〈0.05）. （2） The expressions of HIF-1#alpha# mRNA and protein in hypoxia group and hypoxia + Mn-TBAP group were increased as compared with those in the normal group （P〈0.05）, and these changes were more significant in hypoxia group than those in hypoxia + Mn-TBAP group. （3） The proliferation of PASMCs in hypoxia group was more obvious than that in the normal group and hypoxia + Mn-TBAP group （P〈0.05）, and the proliferation of PASMCs in hypoxia + Mn-TBAP group was increased more significantly than that in the normal group （P〈0.05）. The results indicate that ROS is significantly increased in rat PASMCs under hypoxia, and that ROS affects the expression of HIF-1#alpha# and the proliferation of PASMCs under hypoxia. Therefore, ROS may play an important role in the pathogenesis of pulmonary hypertension and hypoxic signal transductions.

Key words: Hypoxia;Smooth muscle cells;Reactive oxygen species;hypoxia-inducible factor 1;Proliferation

Received: 　　Accepted:

Corresponding author: 　　E-mail:

Citing This Article：

Zhao Jianping, Zhou Zhigang, Hu Hongling, Guo Zhi, Wang Tao, Zhen Guohua, Zhang Zhenxiang. The relationships among reactive oxygen species, hypoxia--inducible factor 1#alpha# and cell proliferation in rat pulmonary arterial smooth muscle cells under hypoxia. Acta Physiol Sin 2007; 59 (3): 319-324 (in Chinese with English abstract).