PMID- 26585696
OWN - NLM
STAT- MEDLINE
DCOM- 20170313
LR  - 20220321
IS  - 1745-7262 (Electronic)
IS  - 1008-682X (Print)
IS  - 1008-682X (Linking)
VI  - 18
IP  - 5
DP  - 2016 Sep-Oct
TI  - Demethylation treatment restores erectile function in a rat model of 
      hyperhomocysteinemia.
PG  - 763-8
LID - 10.4103/1008-682X.163271 [doi]
AB  - 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 cavernosa 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 lower-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 pathogenesis, and demethylation offers a potential new strategy for ED 
      treatment.
FAU - Zhang, Zheng
AU  - Zhang Z
AD  - Department of Andrology, Affiliated Drum Tower Hospital, School of Medicine, 
      Nanjing University, Nanjing, China.
FAU - Zhu, Lei-Lei
AU  - Zhu LL
AD  - Department of Andrology, Affiliated Drum Tower Hospital, School of Medicine, 
      Nanjing University, Nanjing, China.
FAU - Jiang, He-Song
AU  - Jiang HS
AD  - Department of Andrology, Affiliated Drum Tower Hospital, School of Medicine, 
      Nanjing University, Nanjing, China.
FAU - Chen, Hai
AU  - Chen H
AD  - Department of Andrology, Affiliated Drum Tower Hospital, School of Medicine, 
      Nanjing University, Nanjing, China.
FAU - Chen, Yun
AU  - Chen Y
AD  - Department of Andrology, Affiliated Drum Tower Hospital, School of Medicine, 
      Nanjing University, Nanjing, China.
FAU - Dai, Yu-Tian
AU  - Dai YT
AD  - Department of Andrology, Affiliated Drum Tower Hospital, School of Medicine, 
      Nanjing University, Nanjing, China.
LA  - eng
PT  - Journal Article
PL  - China
TA  - Asian J Androl
JT  - Asian journal of andrology
JID - 100942132
RN  - 0LVT1QZ0BA (Homocysteine)
RN  - 31C4KY9ESH (Nitric Oxide)
RN  - EC 3.5.- (Amidohydrolases)
RN  - EC 3.5.3.18 (dimethylargininase)
RN  - H2D2X058MU (Cyclic GMP)
RN  - M801H13NRU (Azacitidine)
SB  - IM
MH  - Amidohydrolases/metabolism
MH  - Animals
MH  - Azacitidine/*therapeutic use
MH  - Cyclic GMP/blood
MH  - Disease Models, Animal
MH  - Down-Regulation
MH  - Erectile Dysfunction/*drug therapy/etiology
MH  - Homocysteine/*blood
MH  - Hyperhomocysteinemia/complications/*drug therapy
MH  - Male
MH  - Nitric Oxide/blood
MH  - Penis/*metabolism
MH  - Promoter Regions, Genetic
MH  - Rats
MH  - Rats, Sprague-Dawley
PMC - PMC5000801
EDAT- 2015/11/21 06:00
MHDA- 2017/03/14 06:00
PMCR- 2016/09/01
CRDT- 2015/11/21 06:00
PHST- 2015/11/21 06:00 [entrez]
PHST- 2015/11/21 06:00 [pubmed]
PHST- 2017/03/14 06:00 [medline]
PHST- 2016/09/01 00:00 [pmc-release]
AID - 163271 [pii]
AID - AJA-18-763 [pii]
AID - 10.4103/1008-682X.163271 [doi]
PST - ppublish
SO  - Asian J Androl. 2016 Sep-Oct;18(5):763-8. doi: 10.4103/1008-682X.163271.