The Role of Intermittent Hypoxia on the Proliferative Inhibition of Rat Cerebellar Astrocytes

Sheng-Chun Chiu; Yu-Jou Lin; Sung-Ying Huang; Chih-Feng Lien; Shee-Ping Chen; Cheng-Yoong Pang; Jian-Hong Lin; Kun-Ta Yang

doi:10.1371/journal.pone.0132263

The Role of Intermittent Hypoxia on the Proliferative Inhibition of Rat Cerebellar Astrocytes

PLoS One. 2015 Jul 14;10(7):e0132263. doi: 10.1371/journal.pone.0132263. eCollection 2015.

Authors

Sheng-Chun Chiu¹, Yu-Jou Lin², Sung-Ying Huang³, Chih-Feng Lien⁴, Shee-Ping Chen⁵, Cheng-Yoong Pang⁶, Jian-Hong Lin⁷, Kun-Ta Yang⁸

Affiliations

¹ Department of Research, Taichung Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Taichung, Taiwan.
² Physiological and Anatomical Medicine, School of Medicine, Tzu Chi University, Hualien, Taiwan.
³ Department of Ophthalmology, Mackay Memorial Hospital, Hsinchu, Taiwan.
⁴ Institute of Medical Sciences, School of Medicine, Tzu Chi University, Hualien, Taiwan.
⁵ Tzu Chi Stem Cells Center, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Hualien, Taiwan.
⁶ Institute of Medical Sciences, School of Medicine, Tzu Chi University, Hualien, Taiwan; Department of Medical Research, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Hualien, Taiwan.
⁷ PhD program in Pharmacology and Toxicology, Tzu Chi University, Hualien, Taiwan.
⁸ Physiological and Anatomical Medicine, School of Medicine, Tzu Chi University, Hualien, Taiwan; Department of Physiology, School of Medicine, Tzu Chi University, Hualien, Taiwan.

Abstract

Sleep apnea syndrome, characterized by intermittent hypoxia (IH), is linked with increased oxidative stress. This study investigates the mechanisms underlying IH and the effects of IH-induced oxidative stress on cerebellar astrocytes. Rat primary cerebellar astrocytes were kept in an incubator with an oscillating O2 concentration between 20% and 5% every 30 min for 1-4 days. Although the cell loss increased with the duration, the IH incubation didn't induce apoptosis or necrosis, but rather a G0/G1 cell cycle arrest of cerebellar astrocytes was noted. ROS accumulation was associated with cell loss during IH. PARP activation, resulting in p21 activation and cyclin D1 degradation was associated with cell cycle G0/G1 arrest of IH-treated cerebellar astrocytes. Our results suggest that IH induces cell loss by enhancing oxidative stress, PARP activation and cell cycle G0/G1 arrest in rat primary cerebellar astrocytes.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Antioxidants / pharmacology
Astrocytes / cytology*
Astrocytes / drug effects
Astrocytes / metabolism
Cell Hypoxia / drug effects
Cell Proliferation / drug effects
Cerebellum / cytology*
Cyclin-Dependent Kinase Inhibitor p21 / metabolism
Enzyme Activation / drug effects
Female
G1 Phase Cell Cycle Checkpoints / drug effects
Male
Oxidative Stress / drug effects
Poly(ADP-ribose) Polymerase Inhibitors / pharmacology
Poly(ADP-ribose) Polymerases / metabolism
Rats
Rats, Sprague-Dawley
Reactive Oxygen Species / metabolism
Resting Phase, Cell Cycle / drug effects

Substances

Antioxidants
Cyclin-Dependent Kinase Inhibitor p21
Poly(ADP-ribose) Polymerase Inhibitors
Reactive Oxygen Species
Poly(ADP-ribose) Polymerases

Grants and funding

This research was supported by grants TCRPP100007, TCIRP98002-1 and TCIRP 95004-05 from Tzu Chi University, Taiwan, ROC.