Effect of intermittent hypoxia on rat INS-1 cells and the protective effect of melatonin

W. Lu, L. Liu, H. Li, G. Li, N. Yu, D.-L. Wang, W. Wang, J. Kang

Institute of Respiratory Diseases, First Affiliated Hospital of China Medical University, Shenyang, China. jiankangdoc@163.com

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• Pharmacology
• Respiratory Medicine

OBJECTIVES: This study aimed to observe the influence of intermittent hypoxia on rat INS-1 cells and the protective effect of melatonin (MT).

MATERIALS AND METHODS: Intermittent hypoxia condition was induced in rat INS-1 cells. The supernatants were used to detect oxidative stress indicators, and the cells were used to detect JNK1 mRNA and JNK1/2 protein. After different dose-dependent interventions of MT, the cells were harvested to observe corresponding oxidative stress indicators and JNK1/2 protein change.

RESULTS: With prolonged exposure time, malondialdehyde (MDA) increased in cultured supernatants whereas superoxide dismutase (SOD) activity decreased. Cells with intermittent hypoxia showed significantly increased JNK1 mRNA expression, whereas phosphorylated JNK1 was highly expressed on the third day. With increased MT dose, MDA in cultured supernatants decreased whereas SOD activity increased. In the group dosed with 100 µM MT, phosphorylated JNK1 protein expression significantly decreased.

CONCLUSIONS: Intermittent hypoxia can cause oxidative damage to INS-1 cells possibly by increasing the JNK1 transcription level and protein activation. A high dose of MT (100 µM) can protect INS-1 cells from oxidative damage induced by intermittent hypoxia.

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