Novel complexes of guanylate cyclase with heat shock protein 90 and nitric oxide synthase

Richard C. Venema, Virginia J. Venema, Hong Ju, M. Brennan Harris, Connie Snead, Tamas Jilling, Christiana Dimitropoulou, Michael E. Maragoudakis, John D. Catravas

Research output: Contribution to journalArticle

101 Citations (Scopus)

Abstract

Soluble guanylate cyclase (sGC) is an important downstream intracellular target of nitric oxide (NO) that is produced by endothelial NO synthase (eNOS) and inducible NO synthase (iNOS). In this study, we demonstrate that sGC exists in a complex with eNOS and heat shock protein 90 (HSP90) in aortic endothelial cells. In addition, we show that in aortic smooth muscle cells, sGC forms a complex with HSP90. Formation of the sGC/eNOS/HSP90 complex is increased in response to eNOS-activating agonists in a manner that depends on HSP90 activity. In vitro binding assays with glutathione S-transferase fusion proteins that contain the α- or β-subunit of sGC show that the sGC β-subunit interacts directly with HSP90 and indirectly with eNOS. Confocal immunofluorescent studies confirm the subcellular colocalization of sGC and HSP90 in both endothelial and smooth muscle cells. Complex formation of sGC with HSP90 facilitates responses to NO donors in cultured cells (cGMP accumulation) as well as in anesthetized rats (hypotension). These complexes likely function to stabilize sGC as well as to provide directed intracellular transfer of NO from NOS to sGC, thus preventing inactivation of NO by superoxide anion and formation of peroxynitrite, which is a toxic molecule that has been implicated in the pathology of several vascular diseases.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume285
Issue number2 54-2
StatePublished - Aug 1 2003

Fingerprint

HSP90 Heat-Shock Proteins
Guanylate Cyclase
Nitric Oxide Synthase
Nitric Oxide
Smooth Muscle Myocytes
Soluble Guanylyl Cyclase
Peroxynitrous Acid
Nitric Oxide Donors
Nitric Oxide Synthase Type III
Poisons
Nitric Oxide Synthase Type II
Glutathione Transferase
Vascular Diseases
Superoxides
Hypotension
Cultured Cells
Endothelial Cells
Pathology

Keywords

  • Bradykinin
  • cGMP accumulation
  • Endothelium
  • Smooth muscle cells
  • Vascular endothelial growth factor

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

Cite this

Venema, R. C., Venema, V. J., Ju, H., Harris, M. B., Snead, C., Jilling, T., ... Catravas, J. D. (2003). Novel complexes of guanylate cyclase with heat shock protein 90 and nitric oxide synthase. American Journal of Physiology - Heart and Circulatory Physiology, 285(2 54-2).

Novel complexes of guanylate cyclase with heat shock protein 90 and nitric oxide synthase. / Venema, Richard C.; Venema, Virginia J.; Ju, Hong; Harris, M. Brennan; Snead, Connie; Jilling, Tamas; Dimitropoulou, Christiana; Maragoudakis, Michael E.; Catravas, John D.

In: American Journal of Physiology - Heart and Circulatory Physiology, Vol. 285, No. 2 54-2, 01.08.2003.

Research output: Contribution to journalArticle

Venema, RC, Venema, VJ, Ju, H, Harris, MB, Snead, C, Jilling, T, Dimitropoulou, C, Maragoudakis, ME & Catravas, JD 2003, 'Novel complexes of guanylate cyclase with heat shock protein 90 and nitric oxide synthase', American Journal of Physiology - Heart and Circulatory Physiology, vol. 285, no. 2 54-2.
Venema, Richard C. ; Venema, Virginia J. ; Ju, Hong ; Harris, M. Brennan ; Snead, Connie ; Jilling, Tamas ; Dimitropoulou, Christiana ; Maragoudakis, Michael E. ; Catravas, John D. / Novel complexes of guanylate cyclase with heat shock protein 90 and nitric oxide synthase. In: American Journal of Physiology - Heart and Circulatory Physiology. 2003 ; Vol. 285, No. 2 54-2.
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