PMID- 28076881
OWN - NLM
STAT- MEDLINE
DCOM- 20171207
LR  - 20181113
IS  - 2047-2927 (Electronic)
IS  - 2047-2919 (Print)
IS  - 2047-2919 (Linking)
VI  - 5
IP  - 2
DP  - 2017 Mar
TI  - Constitutive NOS uncoupling and NADPH oxidase upregulation in the penis of type 2 
      diabetic men with erectile dysfunction.
PG  - 294-298
LID - 10.1111/andr.12313 [doi]
AB  - Erectile dysfunction (ED) associated with type 2 diabetes mellitus (T2DM) 
      involves dysfunctional nitric oxide (NO) signaling and increased oxidative stress 
      in the penis. However, the mechanisms of endothelial NO synthase (eNOS) and 
      neuronal NO synthase (nNOS) dysregulation, and the sources of oxidative stress, 
      are not well defined, particularly at the human level. The objective of this 
      study was to define whether uncoupled eNOS and nNOS, and NADPH oxidase 
      upregulation, contribute to the pathogenesis of ED in T2DM men. Penile erectile 
      tissue was obtained from 9 T2DM patients with ED who underwent penile prosthesis 
      surgery for ED, and from six control patients without T2DM or ED who underwent 
      penectomy for penile cancer. The dimer-to-monomer protein expression ratio, an 
      indicator of uncoupling for both eNOS and nNOS, total protein expressions of eNOS 
      and nNOS, as well as protein expressions of NADPH oxidase catalytic subunit 
      gp91phox (an enzymatic source of oxidative stress) and 4-hydroxy-2-nonenal 
      [4-HNE] and nitrotyrosine (markers of oxidative stress) were measured by western 
      blot in this tissue. In the erectile tissue of T2DM men, eNOS and nNOS uncoupling 
      and protein expressions of NADPH oxidase subunit gp91phox, 4-HNE- and 
      nitrotyrosine-modified proteins were significantly (p < 0.05) increased compared 
      to control values. Total eNOS and nNOS protein expressions were not significantly 
      different between the groups. In conclusion, mechanisms of T2DM-associated ED in 
      the human penis may involve uncoupled eNOS and nNOS and NADPH oxidase 
      upregulation. Our description of molecular factors contributing to the 
      pathogenesis of T2DM-associated ED at the human level is relevant to advancing 
      clinically therapeutic approaches to restore erectile function in T2DM patients.
CI  - (c) 2017 American Society of Andrology and European Academy of Andrology.
FAU - Musicki, B
AU  - Musicki B
AD  - The James Buchanan Brady Urological Institute and Department of Urology, The 
      Johns Hopkins School of Medicine, Baltimore, MD, USA.
FAU - Burnett, A L
AU  - Burnett AL
AD  - The James Buchanan Brady Urological Institute and Department of Urology, The 
      Johns Hopkins School of Medicine, Baltimore, MD, USA.
LA  - eng
GR  - R01 DK067223/DK/NIDDK NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20170111
PL  - England
TA  - Andrology
JT  - Andrology
JID - 101585129
RN  - 0 (Reactive Oxygen Species)
RN  - EC 1.14.13.39 (Nitric Oxide Synthase)
RN  - EC 1.6.3.- (NADPH Oxidases)
SB  - IM
MH  - Aged
MH  - Diabetes Mellitus, Type 2/complications/*metabolism
MH  - Erectile Dysfunction/etiology/*metabolism
MH  - Humans
MH  - Male
MH  - Middle Aged
MH  - NADPH Oxidases/*metabolism
MH  - Nitric Oxide Synthase/*metabolism
MH  - Oxidative Stress/*physiology
MH  - Penis/*metabolism
MH  - Reactive Oxygen Species/metabolism
MH  - Signal Transduction/physiology
MH  - Up-Regulation/physiology
PMC - PMC5352463
MID - NIHMS830886
OTO - NOTNLM
OT  - eNOS uncoupling
OT  - human
OT  - nNOS uncoupling
OT  - oxidative stress
EDAT- 2017/01/12 06:00
MHDA- 2017/12/08 06:00
PMCR- 2018/03/01
CRDT- 2017/01/12 06:00
PHST- 2016/08/10 00:00 [received]
PHST- 2016/10/24 00:00 [revised]
PHST- 2016/11/15 00:00 [accepted]
PHST- 2017/01/12 06:00 [pubmed]
PHST- 2017/12/08 06:00 [medline]
PHST- 2017/01/12 06:00 [entrez]
PHST- 2018/03/01 00:00 [pmc-release]
AID - 10.1111/andr.12313 [doi]
PST - ppublish
SO  - Andrology. 2017 Mar;5(2):294-298. doi: 10.1111/andr.12313. Epub 2017 Jan 11.