Methylation modification is an important cellular mechanism of gene expression regulation. Dimethylarginine dimethylaminohydrolase-2 （DDAH-2） protein is a pivotal molecular for endothelium function. To explore the e...Methylation modification is an important cellular mechanism of gene expression regulation. Dimethylarginine dimethylaminohydrolase-2 （DDAH-2） protein is a pivotal molecular for endothelium function. To explore the effects of 5-aza-deoxycytidine （5-aza）, a demethylation agent, in hyperhomocysteinemia （hhcy）-related erectile dysfunction （ED） rats, 5-aza （1 mg kg-1） was administrated to Sprague-Dawley hhcy-rats induced by supplemented methionine chow diet. Erectile function, nitric oxide-cyclic guanosine monophosphate （NO-cGMP） levels, expression of DDAH-2 protein and promoter methylation status of DDAH-2 were studied in the corpora cavernosa. We found that supplemented methionine diet induced a high homocysteine level after 6 weeks of treatment. DDAH-2 protein was down-regulated in the corpora cavemosa while the administration of 5-aza up-regulated DDAH-2 expression and restored erectile function. The methionine-fed rats showed high methylation levels of DDAH-2 promoter region while the group treated with 5-aza demonstrated Iower-methylation levels when compared to the methionine-fed group. Besides, the administration of 5-aza improved NO and cGMP levels in methionine-fed rats. Therefore, the methylation mechanism involves in ED Dathogenesis. and demethvlation offers a ootential new strate~ for ED treatment.展开更多
文摘Methylation modification is an important cellular mechanism of gene expression regulation. Dimethylarginine dimethylaminohydrolase-2 （DDAH-2） protein is a pivotal molecular for endothelium function. To explore the effects of 5-aza-deoxycytidine （5-aza）, a demethylation agent, in hyperhomocysteinemia （hhcy）-related erectile dysfunction （ED） rats, 5-aza （1 mg kg-1） was administrated to Sprague-Dawley hhcy-rats induced by supplemented methionine chow diet. Erectile function, nitric oxide-cyclic guanosine monophosphate （NO-cGMP） levels, expression of DDAH-2 protein and promoter methylation status of DDAH-2 were studied in the corpora cavernosa. We found that supplemented methionine diet induced a high homocysteine level after 6 weeks of treatment. DDAH-2 protein was down-regulated in the corpora cavemosa while the administration of 5-aza up-regulated DDAH-2 expression and restored erectile function. The methionine-fed rats showed high methylation levels of DDAH-2 promoter region while the group treated with 5-aza demonstrated Iower-methylation levels when compared to the methionine-fed group. Besides, the administration of 5-aza improved NO and cGMP levels in methionine-fed rats. Therefore, the methylation mechanism involves in ED Dathogenesis. and demethvlation offers a ootential new strate~ for ED treatment.
