Demethylation treatment restores erectile function in a rat model of hyperhomocysteinemia
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...
Ausführliche Beschreibung
Autor*in: |
Zheng Zhang [verfasserIn] Lei-Lei Zhu [verfasserIn] He-Song Jiang [verfasserIn] Hai Chen [verfasserIn] Yun Chen [verfasserIn] Yu-Tian Dai [verfasserIn] |
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Format: |
E-Artikel |
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Sprache: |
Englisch |
Erschienen: |
2016 |
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Schlagwörter: |
DDAH-2; erectile dysfunction; hyperhomocysteinemia; methylation |
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Übergeordnetes Werk: |
In: Asian Journal of Andrology - Wolters Kluwer Medknow Publications, 2014, 18(2016), 5, Seite 763-768 |
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Übergeordnetes Werk: |
volume:18 ; year:2016 ; number:5 ; pages:763-768 |
Links: |
Link aufrufen |
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DOI / URN: |
10.4103/1008-682X.163271 |
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Katalog-ID: |
DOAJ009398562 |
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10.4103/1008-682X.163271 doi (DE-627)DOAJ009398562 (DE-599)DOAJa985d32520094118bb33372468d58757 DE-627 ger DE-627 rakwb eng RC870-923 Zheng Zhang verfasserin aut Demethylation treatment restores erectile function in a rat model of hyperhomocysteinemia 2016 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier 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. DDAH-2; erectile dysfunction; hyperhomocysteinemia; methylation Diseases of the genitourinary system. Urology Lei-Lei Zhu verfasserin aut He-Song Jiang verfasserin aut Hai Chen verfasserin aut Yun Chen verfasserin aut Yu-Tian Dai verfasserin aut In Asian Journal of Andrology Wolters Kluwer Medknow Publications, 2014 18(2016), 5, Seite 763-768 (DE-627)352261013 (DE-600)2085228-9 17457262 nnns volume:18 year:2016 number:5 pages:763-768 https://doi.org/10.4103/1008-682X.163271 kostenfrei https://doaj.org/article/a985d32520094118bb33372468d58757 kostenfrei http://www.ajandrology.com/article.asp?issn=1008-682X;year=2016;volume=18;issue=5;spage=763;epage=768;aulast=Zhang kostenfrei https://doaj.org/toc/1008-682X Journal toc kostenfrei https://doaj.org/toc/1745-7262 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2014 GBV_ILN_2153 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 18 2016 5 763-768 |
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10.4103/1008-682X.163271 doi (DE-627)DOAJ009398562 (DE-599)DOAJa985d32520094118bb33372468d58757 DE-627 ger DE-627 rakwb eng RC870-923 Zheng Zhang verfasserin aut Demethylation treatment restores erectile function in a rat model of hyperhomocysteinemia 2016 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier 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. DDAH-2; erectile dysfunction; hyperhomocysteinemia; methylation Diseases of the genitourinary system. Urology Lei-Lei Zhu verfasserin aut He-Song Jiang verfasserin aut Hai Chen verfasserin aut Yun Chen verfasserin aut Yu-Tian Dai verfasserin aut In Asian Journal of Andrology Wolters Kluwer Medknow Publications, 2014 18(2016), 5, Seite 763-768 (DE-627)352261013 (DE-600)2085228-9 17457262 nnns volume:18 year:2016 number:5 pages:763-768 https://doi.org/10.4103/1008-682X.163271 kostenfrei https://doaj.org/article/a985d32520094118bb33372468d58757 kostenfrei http://www.ajandrology.com/article.asp?issn=1008-682X;year=2016;volume=18;issue=5;spage=763;epage=768;aulast=Zhang kostenfrei https://doaj.org/toc/1008-682X Journal toc kostenfrei https://doaj.org/toc/1745-7262 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2014 GBV_ILN_2153 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 18 2016 5 763-768 |
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10.4103/1008-682X.163271 doi (DE-627)DOAJ009398562 (DE-599)DOAJa985d32520094118bb33372468d58757 DE-627 ger DE-627 rakwb eng RC870-923 Zheng Zhang verfasserin aut Demethylation treatment restores erectile function in a rat model of hyperhomocysteinemia 2016 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier 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. DDAH-2; erectile dysfunction; hyperhomocysteinemia; methylation Diseases of the genitourinary system. Urology Lei-Lei Zhu verfasserin aut He-Song Jiang verfasserin aut Hai Chen verfasserin aut Yun Chen verfasserin aut Yu-Tian Dai verfasserin aut In Asian Journal of Andrology Wolters Kluwer Medknow Publications, 2014 18(2016), 5, Seite 763-768 (DE-627)352261013 (DE-600)2085228-9 17457262 nnns volume:18 year:2016 number:5 pages:763-768 https://doi.org/10.4103/1008-682X.163271 kostenfrei https://doaj.org/article/a985d32520094118bb33372468d58757 kostenfrei http://www.ajandrology.com/article.asp?issn=1008-682X;year=2016;volume=18;issue=5;spage=763;epage=768;aulast=Zhang kostenfrei https://doaj.org/toc/1008-682X Journal toc kostenfrei https://doaj.org/toc/1745-7262 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2014 GBV_ILN_2153 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 18 2016 5 763-768 |
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10.4103/1008-682X.163271 doi (DE-627)DOAJ009398562 (DE-599)DOAJa985d32520094118bb33372468d58757 DE-627 ger DE-627 rakwb eng RC870-923 Zheng Zhang verfasserin aut Demethylation treatment restores erectile function in a rat model of hyperhomocysteinemia 2016 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier 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. DDAH-2; erectile dysfunction; hyperhomocysteinemia; methylation Diseases of the genitourinary system. Urology Lei-Lei Zhu verfasserin aut He-Song Jiang verfasserin aut Hai Chen verfasserin aut Yun Chen verfasserin aut Yu-Tian Dai verfasserin aut In Asian Journal of Andrology Wolters Kluwer Medknow Publications, 2014 18(2016), 5, Seite 763-768 (DE-627)352261013 (DE-600)2085228-9 17457262 nnns volume:18 year:2016 number:5 pages:763-768 https://doi.org/10.4103/1008-682X.163271 kostenfrei https://doaj.org/article/a985d32520094118bb33372468d58757 kostenfrei http://www.ajandrology.com/article.asp?issn=1008-682X;year=2016;volume=18;issue=5;spage=763;epage=768;aulast=Zhang kostenfrei https://doaj.org/toc/1008-682X Journal toc kostenfrei https://doaj.org/toc/1745-7262 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2014 GBV_ILN_2153 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 18 2016 5 763-768 |
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10.4103/1008-682X.163271 doi (DE-627)DOAJ009398562 (DE-599)DOAJa985d32520094118bb33372468d58757 DE-627 ger DE-627 rakwb eng RC870-923 Zheng Zhang verfasserin aut Demethylation treatment restores erectile function in a rat model of hyperhomocysteinemia 2016 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier 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. DDAH-2; erectile dysfunction; hyperhomocysteinemia; methylation Diseases of the genitourinary system. Urology Lei-Lei Zhu verfasserin aut He-Song Jiang verfasserin aut Hai Chen verfasserin aut Yun Chen verfasserin aut Yu-Tian Dai verfasserin aut In Asian Journal of Andrology Wolters Kluwer Medknow Publications, 2014 18(2016), 5, Seite 763-768 (DE-627)352261013 (DE-600)2085228-9 17457262 nnns volume:18 year:2016 number:5 pages:763-768 https://doi.org/10.4103/1008-682X.163271 kostenfrei https://doaj.org/article/a985d32520094118bb33372468d58757 kostenfrei http://www.ajandrology.com/article.asp?issn=1008-682X;year=2016;volume=18;issue=5;spage=763;epage=768;aulast=Zhang kostenfrei https://doaj.org/toc/1008-682X Journal toc kostenfrei https://doaj.org/toc/1745-7262 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2014 GBV_ILN_2153 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 18 2016 5 763-768 |
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Zheng Zhang @@aut@@ Lei-Lei Zhu @@aut@@ He-Song Jiang @@aut@@ Hai Chen @@aut@@ Yun Chen @@aut@@ Yu-Tian Dai @@aut@@ |
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Demethylation treatment restores erectile function in a rat model of hyperhomocysteinemia |
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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. |
abstractGer |
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. |
abstract_unstemmed |
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. |
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Demethylation treatment restores erectile function in a rat model of hyperhomocysteinemia |
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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.</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">DDAH-2; erectile dysfunction; hyperhomocysteinemia; methylation</subfield></datafield><datafield tag="653" ind1=" " ind2="0"><subfield code="a">Diseases of the genitourinary system. 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