Expression of major HDL-associated antioxidant PON-1 is gender dependent and regulated during inflammation.
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.
bin Ali
Azhar
A
National University Medical Institutes, The National University of Singapore, Singapore, Singapore.
Zhang
Qian
Q
Lim
Yew Koon
YK
Fang
Dong
D
Retnam
Leslie
L
Lim
Sai-Kiang
SK
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D000975:Antioxidants / Q000737:chemistry*; D043303:Aryldialkylphosphatase / Q000096:biosynthesis*; D015152:Blotting, Northern; D002460:Cell Line; D045744:Cell Line, Tumor; D003907:Dexamethasone / Q000378:metabolism; D005260:Female; D015971:Gene Expression Regulation, Enzymologic; D007249:Inflammation; D008070:Lipopolysaccharides / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012737:Sex Factors; D013997:Time Factors; D014018:Tissue Distribution
D000893:Anti-Inflammatory Agents; D000975:Antioxidants; D008070:Lipopolysaccharides; D012333:RNA, Messenger; D003907:Dexamethasone; D043303:Aryldialkylphosphatase