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

Eginhard Waldkirch, Stefan Uckert, Katja Sigl, Florian Imkamp, Kristina Langnaese, Karin Richter, Udo Jonas, Michael Sohn, Christian Stief, Gerald Wolf, Petter Hedlund

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

Introduction. 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) α isoform has been linked to erectile dysfunction and diabetes mellitus. So far, the expression of cGKI α and β isoforms has not been evaluated in human penile erectile tissue. Aim. To evaluate the expression of cGKI α and β isoforms in relation to smooth muscle α-actin, cGMP, and endothelial NO synthase (eNOS) in human cavernous arteries (HCAs) and human corpus cavernosum (HCC). Methods. Cryostat sections of HCA and HCC were incubated with primary antibodies directed against α-actin, cGMP, eNOS, cGKI, cGKI α, and cGKI β. 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. Main Outcome Measures. Expression of cGKI α and β isoforms in relation to smooth muscle α-actin, cGMP, and eNOS in human penile erectile tissue. Results. Immunoreactivities specific for cGKI, cGKI α, and cGKI β 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. Conclusions. Our results demonstrate, for the first time, the expression of both cGKI α and β isoforms in the smooth musculature of HCA and HCC. Corresponding to recent findings from animal studies, the presence of cGKI α and β provides further evidence for a significant role of these enzymes in the control of smooth muscle function in human penile erectile tissue.

Original languageEnglish
Pages (from-to)536-543
Number of pages8
JournalJournal of Sexual Medicine
Volume5
Issue number3
DOIs
Publication statusPublished - Mar 2008

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Cyclic GMP-Dependent Protein Kinases
Protein Isoforms
Actins
Arteries
Nitric Oxide Synthase
Smooth Muscle
Penile Diseases
Western Blotting
Staining and Labeling
Nitric Oxide Synthase Type III
Guanine
Erectile Dysfunction
Vascular Diseases

Keywords

  • Cavernous arteries
  • Corpus cavernosum
  • Cyclic GMP
  • Erectile dysfunction
  • Nitric oxide
  • Protein kinase G

ASJC Scopus subject areas

  • Urology
  • Obstetrics and Gynaecology

Cite this

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; Wolf, Gerald; Hedlund, Petter.

In: Journal of Sexual Medicine, Vol. 5, No. 3, 03.2008, p. 536-543.

Research output: Contribution to journalArticle

Waldkirch, E, Uckert, S, Sigl, K, Imkamp, F, Langnaese, K, Richter, K, Jonas, U, Sohn, M, Stief, C, Wolf, G & Hedlund, P 2008, 'Expression and distribution of cyclic GMP-dependent protein kinase-1 isoforms in human penile erectile tissue', Journal of Sexual Medicine, vol. 5, no. 3, pp. 536-543. https://doi.org/10.1111/j.1743-6109.2007.00735.x
Waldkirch, Eginhard ; Uckert, Stefan ; Sigl, Katja ; Imkamp, Florian ; Langnaese, Kristina ; Richter, Karin ; Jonas, Udo ; Sohn, Michael ; Stief, Christian ; Wolf, Gerald ; Hedlund, Petter. / Expression and distribution of cyclic GMP-dependent protein kinase-1 isoforms in human penile erectile tissue. In: Journal of Sexual Medicine. 2008 ; Vol. 5, No. 3. pp. 536-543.
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AU - Waldkirch, Eginhard

AU - Uckert, Stefan

AU - Sigl, Katja

AU - Imkamp, Florian

AU - Langnaese, Kristina

AU - Richter, Karin

AU - Jonas, Udo

AU - Sohn, Michael

AU - Stief, Christian

AU - Wolf, Gerald

AU - Hedlund, Petter

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N2 - Introduction. 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) α isoform has been linked to erectile dysfunction and diabetes mellitus. So far, the expression of cGKI α and β isoforms has not been evaluated in human penile erectile tissue. Aim. To evaluate the expression of cGKI α and β isoforms in relation to smooth muscle α-actin, cGMP, and endothelial NO synthase (eNOS) in human cavernous arteries (HCAs) and human corpus cavernosum (HCC). Methods. Cryostat sections of HCA and HCC were incubated with primary antibodies directed against α-actin, cGMP, eNOS, cGKI, cGKI α, and cGKI β. 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. Main Outcome Measures. Expression of cGKI α and β isoforms in relation to smooth muscle α-actin, cGMP, and eNOS in human penile erectile tissue. Results. Immunoreactivities specific for cGKI, cGKI α, and cGKI β 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. Conclusions. Our results demonstrate, for the first time, the expression of both cGKI α and β isoforms in the smooth musculature of HCA and HCC. Corresponding to recent findings from animal studies, the presence of cGKI α and β provides further evidence for a significant role of these enzymes in the control of smooth muscle function in human penile erectile tissue.

AB - Introduction. 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) α isoform has been linked to erectile dysfunction and diabetes mellitus. So far, the expression of cGKI α and β isoforms has not been evaluated in human penile erectile tissue. Aim. To evaluate the expression of cGKI α and β isoforms in relation to smooth muscle α-actin, cGMP, and endothelial NO synthase (eNOS) in human cavernous arteries (HCAs) and human corpus cavernosum (HCC). Methods. Cryostat sections of HCA and HCC were incubated with primary antibodies directed against α-actin, cGMP, eNOS, cGKI, cGKI α, and cGKI β. 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. Main Outcome Measures. Expression of cGKI α and β isoforms in relation to smooth muscle α-actin, cGMP, and eNOS in human penile erectile tissue. Results. Immunoreactivities specific for cGKI, cGKI α, and cGKI β 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. Conclusions. Our results demonstrate, for the first time, the expression of both cGKI α and β isoforms in the smooth musculature of HCA and HCC. Corresponding to recent findings from animal studies, the presence of cGKI α and β provides further evidence for a significant role of these enzymes in the control of smooth muscle function in human penile erectile tissue.

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KW - Corpus cavernosum

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KW - Erectile dysfunction

KW - Nitric oxide

KW - Protein kinase G

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