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Expression and distribution of cyclic GMP-dependent protein kinase-1 isoforms in human penile erectile tissue

Waldkirch, Eginhard; Uckert, Stefan; Sigl, Katja; Imkamp, Florian; Langnaese, Kristina; Richter, Karin; Jonas, Udo; Sohn, Michael; Stief, Christian and Wolf, Gerald, et al. (2008) In Journal of Sexual Medicine 5(3). p.536-543
Abstract
Besides the bioavailability of nitric oxide (NO), downstream guanine monophosphate (cGMP) effector proteins are also considered to play a significant role in penile vascular disease. In animal studies, a downregulation of the cGMP-dependent protein kinase-1 (cGKI) alpha isoform has been linked to erectile dysfunction and diabetes mellitus. So far, the expression of cGKI alpha and beta isoforms has not been evaluated in human penile erectile tissue. To evaluate the expression of cGKI alpha and beta isoforms in relation to smooth muscle alpha-actin, cGMP, and endothelial NO synthase (eNOS) in human cavernous arteries (HCAs) and human corpus cavernosum (HCC). Cryostat sections of HCA and HCC were incubated with primary antibodies directed... (More)
Besides the bioavailability of nitric oxide (NO), downstream guanine monophosphate (cGMP) effector proteins are also considered to play a significant role in penile vascular disease. In animal studies, a downregulation of the cGMP-dependent protein kinase-1 (cGKI) alpha isoform has been linked to erectile dysfunction and diabetes mellitus. So far, the expression of cGKI alpha and beta isoforms has not been evaluated in human penile erectile tissue. To evaluate the expression of cGKI alpha and beta isoforms in relation to smooth muscle alpha-actin, cGMP, and endothelial NO synthase (eNOS) in human cavernous arteries (HCAs) and human corpus cavernosum (HCC). Cryostat sections of HCA and HCC were incubated with primary antibodies directed against alpha-actin, cGMP, eNOS, cGKI, cGKI alpha, and cGKI beta. Visualization of double-labeled immunofluorescent stainings was achieved by laser microscopy. Western blot analysis was performed in order to confirm the expression of cGKI isoforms. Expression of cGKI alpha and beta isoforms in relation to smooth muscle alpha-actin, cGMP, and eNOS in human penile erectile tissue. Immunoreactivities specific for cGKI, cGKI alpha, and cGKI beta were observed within the smooth musculature and the endothelium of cavernous arteries and sinusoids. Double stainings revealed the colocalization of alpha-actin, cGMP, eNOS, and cGKI isoforms. The expression of cGKI isoforms was confirmed by Western blot analysis. Our results demonstrate, for the first time, the expression of both cGKI alpha and beta isoforms in the smooth musculature of HCA and HCC. Corresponding to recent findings from animal studies, the presence of cGKI alpha and beta provides further evidence for a significant role of these enzymes in the control of smooth muscle function in human penile erectile tissue. (Less)
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Contribution to journal
publication status
published
subject
keywords
cavernosum, corpus, cavernous arteries, cyclic gmp, erectile dysfunction, nitric oxide, protein kinase G
in
Journal of Sexual Medicine
volume
5
issue
3
pages
536 - 543
publisher
Wiley-Blackwell
external identifiers
  • wos:000253630700014
  • scopus:40349105766
ISSN
1743-6109
DOI
10.1111/j.1743-6109.2007.00735.x
language
English
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yes
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f3635aba-c569-4a4f-8b20-ff470a58dce8 (old id 1192844)
date added to LUP
2008-09-09 08:59:46
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2017-08-20 03:42:37
@article{f3635aba-c569-4a4f-8b20-ff470a58dce8,
  abstract     = {Besides the bioavailability of nitric oxide (NO), downstream guanine monophosphate (cGMP) effector proteins are also considered to play a significant role in penile vascular disease. In animal studies, a downregulation of the cGMP-dependent protein kinase-1 (cGKI) alpha isoform has been linked to erectile dysfunction and diabetes mellitus. So far, the expression of cGKI alpha and beta isoforms has not been evaluated in human penile erectile tissue. To evaluate the expression of cGKI alpha and beta isoforms in relation to smooth muscle alpha-actin, cGMP, and endothelial NO synthase (eNOS) in human cavernous arteries (HCAs) and human corpus cavernosum (HCC). Cryostat sections of HCA and HCC were incubated with primary antibodies directed against alpha-actin, cGMP, eNOS, cGKI, cGKI alpha, and cGKI beta. Visualization of double-labeled immunofluorescent stainings was achieved by laser microscopy. Western blot analysis was performed in order to confirm the expression of cGKI isoforms. Expression of cGKI alpha and beta isoforms in relation to smooth muscle alpha-actin, cGMP, and eNOS in human penile erectile tissue. Immunoreactivities specific for cGKI, cGKI alpha, and cGKI beta were observed within the smooth musculature and the endothelium of cavernous arteries and sinusoids. Double stainings revealed the colocalization of alpha-actin, cGMP, eNOS, and cGKI isoforms. The expression of cGKI isoforms was confirmed by Western blot analysis. Our results demonstrate, for the first time, the expression of both cGKI alpha and beta isoforms in the smooth musculature of HCA and HCC. Corresponding to recent findings from animal studies, the presence of cGKI alpha and beta provides further evidence for a significant role of these enzymes in the control of smooth muscle function in human penile erectile tissue.},
  author       = {Waldkirch, Eginhard and Uckert, Stefan and Sigl, Katja and Imkamp, Florian and Langnaese, Kristina and Richter, Karin and Jonas, Udo and Sohn, Michael and Stief, Christian and Wolf, Gerald and Hedlund, Petter},
  issn         = {1743-6109},
  keyword      = {cavernosum,corpus,cavernous arteries,cyclic gmp,erectile dysfunction,nitric oxide,protein kinase G},
  language     = {eng},
  number       = {3},
  pages        = {536--543},
  publisher    = {Wiley-Blackwell},
  series       = {Journal of Sexual Medicine},
  title        = {Expression and distribution of cyclic GMP-dependent protein kinase-1 isoforms in human penile erectile tissue},
  url          = {http://dx.doi.org/10.1111/j.1743-6109.2007.00735.x},
  volume       = {5},
  year         = {2008},
}