Irreversible Inflammation is Associated with Decreased Levels of the α 1 -,β 1 -,and α 2 -Subunits of sGC in Human Odontoblasts

Abstract

The nitric oxide (NO) receptor enzyme soluble guanylate cyclase (sGC) contains one prosthetic heme group as an αβ heterodimer, and two heterodimer isoforms (α₁β₁, α₂β₁) were characterized to have enzyme activity. To test the irreversible inflammation-dependent regulation of sGC in odontoblasts, we incubated decalcified frozen sections of healthy and inflamed human third molars with antibodies against β-actin, nitrotyrosine, inducible nitric oxide synthase (iNOS), α₁-, β₁-, and α₂-subunits of sGC and analyzed them at protein levels by quantitative immunohistochemistry. The irreversible inflammation induced an increase in the signal intensities for nitrotyrosine and iNOS and a decrease for the α₁-, β₁-, and α₂-subunits of sGC in odontoblasts. Inflammatory mediators, reactive oxygen, and nitrogen species may impair the expression of the α₁-, β₁-, and α₂-subunits in odontoblasts. The decrease of sGC at the protein level in inflamed odontoblasts is compatible with a critical role for sGC to mediate biological effects of NO in health.

Keywords

soluble guanylate cyclase odontoblasts inflammation reactive oxygen species reactive nitrogen species

Get full access to this article

View all access options for this article.

References

Baltrons

Pifarre

Berciano

Lafarga

Garcia

(2008). LPS-induced down-regulation of NO-sensitive guanylyl cyclase in astrocytes occurs by proteosomal degradation in clastosomes. Mol Cell Neurosci 37:494-506.

Bamberger

Koglin

Kempfert

Löning

Scholz

Behrends

(2001). Expression and tissue localization of soluble guanylyl cyclase in the human placenta using novel antibodies directed against the α₂ subunit. J Clin Endocrinol Metab 86:909-912.

Behrends

Harteneck

Schultz

Koesling

(1995). A variant of the α₂ subunit of soluble guanylyl cyclase contains an insert homologous to a region within adenylyl cyclases and functions as a dominant negative protein. J Biol Chem 270:21109-21113.

Behrends

Kempfert

Mietens

Koglin

Scholz

Middendorff

(2001). Developmental changes of nitric oxide-sensitive guanylyl cyclase expression in pulmonary arteries. Biochem Biophys Res Commun 283:883-887.

Bogdan

(2001). Nitric oxide and the immune response. Nat Immunol 2:907-916.

Buechler

Nakane

Murad

(1991). Expression of soluble guanylate cyclase activity requires both enzyme subunits. Biochem Biophys Res Commun 174:351-357.

Burette

Zabel

Weinberg

Schmidt

Valtschanoff

(2002). Synaptic localization of nitric oxide synthase and soluble guanylyl cyclase in the hippocampus. J Neurosci 22:8961-8970.

Di Nardo Di Maio

Lohinai

D’Arcangelo

De Fazio

Speranza

De Lutiis

. (2004). Nitric oxide synthase in healthy and inflamed human dental pulp. J Dent Res 83:312-316.

Felaco

Di Maio

De Fazio

D’Arcangelo

De Lutiis

Varvara

. (2000). Localization of the e-NOS enzyme in endothelial cells and odontoblasts of healthy human dental pulp. Life Sci 68:297-306.

10.

Fleming

(2010). Molecular mechanisms underlying the activation of eNOS. Pflügers Arch 459:793-806.

11.

Glynos

Kotanidou

Orfanos

Zhou

Simoes

DCM

Magkou

. (2007). Soluble guanylyl cyclase expression is reduced in LPS-induced lung injury. Am J Physiol Regul Integr Comp Physiol 292:R1448-R1455.

12.

Goldberg

Farges

Lacerda-Pinheiro

Six

Jegat

Decup

. (2008). Inflammatory and immunological aspects of dental pulp repair. Pharmacol Res 58:137-147.

13.

Hikiji

Shin

Oida

Takato

Koizumi

Toyo-oka

(1997). Direct action of nitric oxide on osteoblastic differentiation. FEBS Lett 410:238-242.

14.

Inoue

Hiruma

Hirose

Yamaguchi

Hagiwara

(1995). Reciprocal regulation by cyclic nucleotides of the differentiation of rat osteoblast-like cells and mineralization of nodules. Biochem Biophs Res Commun 215:1104-1110.

15.

Koglin

Behrends

(2003). A functional domain of the α subunit of soluble guanylyl cyclase is necessary for activation of the enzyme by nitric oxide and YC-1 but is not involved in heme binding. J Biol Chem 278:12590-12597.

16.

Korkmaz

Baumann

Steinritz

Schröder

Behrends

Addicks

. (2005). NO-cGMP signaling molecules in cells of the rat molar dentin-pulp complex. J Dent Res 84:618-623.

17.

Korkmaz

Bloch

Steinritz

Baumann

Addicks

Schneider

. (2006). Bradykinin mediates phosphorylation of eNOS in odontoblasts. J Dent Res 85:536-541.

18.

Krumenacker

Hanafy

Murad

(2004). Regulation of nitric oxide and soluble guanylyl cyclase. Brain Res Bull 62:505-515.

19.

Meurer

Pioch

Pabst

Opitz

Schmidt

Beckhaus

. (2009). Nitric oxide independent vasodilator rescues heme-oxidized soluble guanylate cyclase from proteosomal degradation. Circ Res 105:33-41.

20.

Nathan

(2006). Neutrophils and immunity: challenges and opportunities. Nat Rev Immunol 6:173-182.

21.

Pedraza

Baltrons

Heneka

Garcia

(2003). Interleukin-1β and lipopolysaccharide decrease soluble guanylyl cyclase in brain cells: NO-independent destabilization of protein and NO-dependent decrease of mRNA. J Neuroimmunol 144:80-90.

22.

Ruetten

Zabel

Linz

Schmidt

(1999). Downregulation of soluble guanylate cyclase in young and aging spontaneously hypertensive rats. Circ Res 85:534-541.

23.

Russwurm

Behrends

Harteneck

Koesling

(1998). Functional properties of a naturally occurring isoform of soluble guanylyl cyclase. Biochem J 335(Pt 1):125-130.

24.

Sardon

Baltrons

Garcia

(2004). Nitric oxide-dependent and independent down-regulation of NO-sensitive guanylyl cyclase in neural cells. Toxicol Lett 149:75-83.

25.

Sayed

Baskaran

van den Akker

Beuve

(2007). Desensitization of soluble guanylyl cyclase, the NO receptor, by S-nitrosylation. Proc Natl Acad Sci USA 104:12312-12317.

26.

Stasch

Schmidt

Nedvetsky

Nedvetskaya

Kumar

Meurer

. (2006). Targeting the heme-oxidized nitric oxide receptor for selective vasodilatation of diseased blood vessels. J Clin Invest 116:2552-2561.

27.

Takata

Filippov

Liu

Ichinose

Janssens

Bloch

. (2001). Cytokines decrease sGC in pulmonary artery smooth muscle cells via NO-dependent and NO-independent mechanisms. Am J Physiol Lung Cell Mol Physiol 280:L272-L278.

28.

Weber

Lauer

Mülsch

Kojda

(2001). The effect of peroxynitrite on the catalytic activity of soluble guanylyl cyclase. Free Radic Biol Med 31:1360-1367.

29.

Zabel

Häusler

Weeger

Schmidt

(1999). Homodimerization of soluble guanylyl cyclase subunits: dimerization analysis using a glutathione S-transferase affinity tag. J Biol Chem 274:18149-18152.

Supplementary Material

Please find the following supplemental material available below.

For Open Access articles published under a Creative Commons License, all supplemental material carries the same license as the article it is associated with.

For non-Open Access articles published, all supplemental material carries a non-exclusive license, and permission requests for re-use of supplemental material or any part of supplemental material shall be sent directly to the copyright owner as specified in the copyright notice associated with the article.

0.00 MB

0.09 MB