Hydrogen sulfide potentiates interleukin-1β-induced nitric oxide production via enhancement of extracellular signal-regulated kinase activation in rat vascular smooth muscle cells
Section snippets
Materials and methods
Materials. Rat recombinant IL-1β, NaHS, l-Cys, H2S gas, dl-propargylglycine (PAG), and HgCl2 were purchased from Sigma–Aldrich (St. Louis, MO). The mitogen-activated protein kinase (MAPK) inhibitors including U0126 for inhibition of an extracellular signal-regulated kinase 1/2 (ERK1/2), SP600125 for inhibition of a c-jun N-terminal kinase (JNK), and SB203580 for inhibition of a p38 MAPK were purchased from Calbiochem (San Diego, CA). Antibodies to iNOS and β-actin were purchased from Santa Cruz
Results
Rat VSMCs have been reported to respond to IL-1β alone with increased NO production and iNOS expression [26]. This response to IL-1β was used in this study as a model system to evaluate the possible effects of H2S on NO production and iNOS expression. NaHS was also used in this study as a source of H2S, because NaHS dissociates to Na+ and HS− in solution, and then HS− associates with H+ to continuously form stable H2S. It was reported that about one-third of the H2S existed as the gaseous form
Discussion
Besides vasodilating effect, NO has inhibitory effects on platelet aggregation, leukocyte adhesion, VSMC proliferation, and migration [15], [16], [17], [18], [19], [20], [21], [22], suggesting an important role of iNOS-derived NO in hypertension, atherosclerosis, and vascular remodeling. In this regard, the present study investigated whether H2S could affect NO production in rat VSMCs. Although the H2S donor NaHS by itself showed no effect on NO production, it augmented IL-1β-induced NO
Acknowledgment
This study was supported by the Korean Research Foundation Grant (KRF-2004-005-E00038).
References (35)
- et al.
Rat cystathionine beta-synthase: expression of four alternatively spliced isoforms in transfected cultured cells
Arch. Biochem. Biophys.
(1992) - et al.
Nitric oxide as a bioregulator of apoptosis
Biochem. Biophys. Res. Commun.
(2001) The role of nitric oxide in hepatic metabolism
Nutrition
(1998)- et al.
Efficient inhibition of intimal hyperplasia by adenovirus-mediated inducible nitric oxide synthase gene transfer to rats and pigs in vivo
J. Am. Coll. Surg.
(1998) - et al.
The possible role of hydrogen sulfide as an endogenous smooth muscle relaxant in synergy with nitric oxide
Biochem. Biophys. Res. Commun.
(1997) - et al.
Evidence for the formation of a novel nitrosothiol from the gaseous mediators nitric oxide and hydrogen sulphide
Biochem. Biophys. Res. Commun.
(2006) - et al.
Catalase potentiates interleukin-1beta-induced expression of nitric oxide synthase in rat vascular smooth muscle cells
Free Radic. Biol. Med.
(2005) - et al.
Temporal control of NF-kappaB activation by ERK differentially regulates interleukin-1beta-induced gene expression
J. Biol. Chem.
(2004) Two’s company, three’s a crowd: can H2S be the third endogenous gaseous transmitter?
FASEB J.
(2002)- et al.
Carbon monoxide and hydrogen sulfide: gaseous messengers in cerebrovascular circulation
J. Appl. Physiol.
(2006)
Hydrogen sulphide and the hyperdynamic circulation in cirrhosis: a hypothesis
Gut
New roles for cysteine and transsulfuration enzymes: production of H2S, a neuromodulator and smooth muscle relaxant
Nutr. Rev.
From O2 to H2S: a landscape view of gas biology
Keio J. Med.
Murine cystathionine γ-lyase: complete complementary DNA and genomic sequences, promoter activity, tissue distribution and developmental expression
Biochem. J.
Hydrogen sulfide-induced relaxation of resistance mesenteric artery beds of rats
Am. J. Physiol. Heart Circ. Physiol.
Down-regulation of endogenous hydrogen sulfide pathway in pulmonary hypertension and pulmonary vascular structural remodeling induced by high pulmonary blood flow in rats
Circ. J.
The role of hydrogen sulfide generation in the pathogenesis of hypertension in rats induced by inhibition of nitric oxide synthase
J. Hypertens.
Cited by (79)
Hydrogen sulfide: From a toxic gas to a potential therapy for COVID-19 and inflammatory disorders
2023, Nitric Oxide - Biology and ChemistryThe Triple Crown: NO, CO, and H<inf>2</inf>S in cancer cell biology
2023, Pharmacology and TherapeuticsUtility of NO and H<inf>2</inf>S donating platforms in managing COVID-19: Rationale and promise
2022, Nitric Oxide - Biology and ChemistryCitation Excerpt :However, there are also reports that NaHS, H2S, or l-cysteine upregulate iNOS [398] or do not affect iNOS levels [423]. Interestingly, both results were seen in one study, demonstrating that H2S administration may produce varying effects in physiological vs. pathological states; although NaHS and l-cysteine increased iNOS expression and NO production by enhancing IL-1β-induced NF-κB activation, it did not affect NO production or iNOS expression when IL-1β stimulation was absent [427]. There is also evidence emphasizing the importance of donor release kinetics and concentration.
Nitric oxide and hydrogen sulfide: Sibling rivalry in the family of epigenetic regulators
2021, Free Radical Biology and MedicineHydrogen sulfide inhibited L-type calcium channels (CaV1.2) via up-regulation of the channel sulfhydration in vascular smooth muscle cells
2019, European Journal of Pharmacology
- 1
These authors contributed equally to this work.