Expression of major HDL-associated antioxidant PON-1 is gender dependent and regulated during inflammation

被引:82
作者
Bin Ali, A
Zhang, Q
Lim, YK
Fang, D
Retnam, L
Lim, SK
机构
[1] Natl Univ Singapore, Genome Inst Singapore, Singapore 117597, Singapore
[2] Natl Univ Singapore, Natl Univ Med Inst, Singapore 117597, Singapore
[3] Natl Univ Singapore, Anim Holding Unit, Singapore 117597, Singapore
基金
英国医学研究理事会;
关键词
paraoxonase; 1; antioxidant; gender; inflammation; HDL; free radicals;
D O I
10.1016/S0891-5849(02)01436-3
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Paraoxonase 1, an HDL-associated enzyme that confers antioxidant activity on HDL, and its activity in serum have been correlated with protection against atherosclerosis, an oxidative disease. However, serum PON-1 activity is highly variable and its regulation is complex, involving both genetic and environmental factors. It is influenced by gender and inflammation, two important factors in atherosclerosis. Serum PON-1 activity has been shown to be lower in male mice and is decreased in male Syrian hamster during inflammation. Here we show that male mice had lower hepatic PON-1 mRNA that increased by 170% after castration. Our data also suggested that this effect was testes but not plasma testosterone dependent. Ovariectomy had no effect on PON-1 mRNA in female mice. LPS caused hepatic PON-1 mRNA to decrease further in male mice, and to increase moderately in female mice. Anti-inflammatory dexamethasone enhanced PON-1 mRNA level by 2-fold in male and female LPS-treated mice, and increased PON-1 expression by 8-fold in Hepa cell, a mouse hepatoma cell line. Therefore, antioxidant PON-1 is regulated at the mRNA level in a gender-specific manner by proinflammatory LPS and anti-inflammatory dexamethasone. (C) 2003 Elsevier Science Inc.
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页码:824 / 829
页数:6
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