Immunohistochemccal approach reveals localizatin of cystathionine--lyase and ccystathionine--synthetase in ethanol-induced gastric mucosa damage in mice

Context Hydrogen sulphide (H2S) has been proved to be a neuromodulator and contributes to the maintenance of gastric mucosal integrity in damage caused by anti-inflammatory nonsteroidal drugs. Previously, we demonstrated that H2S synthesis is essential to gastric protection against ethanol. Objective To better understanding the role of H2S and the detailed localization of its production in both normal and injured stomach due to ethanol injection, we studied the expression of cystathionine-γ-lyase (CSE) and cystathionine-β-synthetase (CBS) isoforms in gastric mucosa of mice treated with saline or 50% ethanol. Methods Mice were treated by gavage with saline or 50% ethanol (0.5 mL/25 g). After 1 hour, mice were sacrificed, and gastric tissue was evaluated by histological and immunohistochemical analysis specific for CSE and CBS. Results We have demonstrated a non-specific expression of CBS in the normal gastric mucosa and expression of CSE occurring mainly in the parietal cells of the animals treated with ethanol. Conclusion Thus, we demonstrated that the expression of CBS appears to be constitutive and diffuse across the gastric epithelium, while the expression of CSE appears to be induced in parietal cells by damage agents such as ethanol. .

Contexto O sulfeto de hidrogênio (H2S) tem sido mostrado como um neuromodulador e contribuidor para a manutenção da integridade da mucosa gástrica na lesão causada por drogas antiinflamatórias não esteroidais. Previamente, demonstramos que a síntese de H2S é essencial para a proteção da mucosa gástrica contra a administração de etanol. Objetivo Para compreender o papel do H2S e a localização detalhada de sua produção no estômago normal e após lesão induzida pela administração de etanol, estudou-se a expressão das isoformas cistationina-γ-liase (CSE) e cistationina-β-sintetase (CBS) na mucosa gástrica de camundongos tratados com salina ou etanol 50%. Métodos Os camundongos foram tratados por gavagem com salina ou etanol 50% (0,5 mL/25 g). Após 1 hora, os camundongos foram sacrificados e os tecidos gástricos foram avaliados por análise histológica e imunoistoquímica específica para CBS e CSE. Resultados Foi demonstrado expressão não específica de CBS na mucosa gástrica normal e expressão de CSE ocorrendo principalmente nas células parietais dos animais tratados com etanol. Conclusão Assim, demonstramos que a expressão de CBS parece ser constitutiva e difusa através do epitélio gástrico, enquanto a expressão de CSE parece ser induzida nas células parietais por agentes lesivos como o etanol. .

Homocysteine, Hydrogen sulfide (H2S) and NMDA-Receptor in Heart Failure.

Mitochondrial mechanism of oxidative stress and matrix metalloproteinase (MMP) activation was unclear. Our recent data suggested that MMPs are localized to mitochondria and activated by peroxynitrite, which causes cardiovascular remodeling and failure. Recently, we have demonstrated that elevated levels of homocysteine (Hcy), known as hyperhomocysteinemia (HHcy) increase oxidative stress in the mitochondria. Although HHcy causes heart failure, interestingly, it is becoming very clear that Hcy can generate hydrogen sulfide (H2S), if the enzymes cystathionine β-synthase (CBS) and cystathionine -lyase (CGL) are present. H2S is a strong anti-oxidant and vasorelaxing agent. Paradoxically, it is interesting that Hcy, a precursor of H2S can be cardioprotective. The CGL is ubiquitous, while the CBS is not present in the vascular tissues. Therefore, under normal condition, only half of Hcy can be converted to H2S. However, there is strong potential for gene therapy of CBS to vascular tissue that can mitigate the detrimental effects of Hcy by converting it to H2S. This scenario is possible, if the activities of both the enzymes (CBS and CGL) are increased in tissues by gene therapy.

Study on Carbon Monoxide Down-Regulating Hydrogen Sulfide Pathway of Vascular Smooth Muscle Cells in Hypertensive Rats / 实用儿科临床杂志

Objective To investigate the effect of carbon monoxide(CO) on hydrogen sulfide(H_2S)/cystathionine-?-lyase system(CSE) in vascular smooth muscle cells(VSMC) of spontaneous hypertensive rats(SHR).Methods The SHR VSMC were divided into 2 groups:experimental group(hemin was added to the culture media at a concentration of 10 ?mol/L)and control group (dimethyl sulfoxide was added to the culture media at an equal volume).The content of H_2S in the cultrue media was measured by sulfide electrode method,and the CSEmRNA level was assayed by competitive reversed transcription-polymerase chain reaction(RT-PCR).Results Compared with control group,the content of H_2S in the culture media of hemin-treated SMCs was significantly lower[(16.03? 2.14) ?mol/L vs (13.31?1.74)?mol/L],and the CSEmRNA level in hemin-treated SMCs was decreased markedly(0.17?0.04 vs 0.13?0.03).Conclusion CO can down-regulate the H_2S/CSE system in SMC of SHR.

Regulatory Effect of Nitric Oxide on Hydrogen Sulfide/ Cystathionine-?-Lyase of Vascular Smooth Muscle Cells in Spontaneously Hypertensive Rats / 实用儿科临床杂志

Objective To investigate the effect of nitric oxide on hydrogen sulfide/ cystathionine-?-lyase(CSE) system in the vascular smooth muscle cells of spontaneously hypertensive rats(SHR).Methods The SHR aortic smooth muscle cells(SMCs) were divided into 2 groups: sodium nitroprusside(SNP) group and control group.The content of hydrogen sulfide in the culture media was measured by sulfide electrode method,and the CSE mRNA level was assayed by competitive reversed transcription-polymerase chain reaction((RT-PCR)).Results Compared with control group,the content of hydrogen sulfide in the culture media of SNP group was significantly higher [(16.16?3.71) ?mol/L vs(22.71?4.84) ?mol/L],and the CSE mRNA level in SMCs in SNP group was lower than that of control group.Conclusion Nitric oxide exerted complicated effect on the hydrogen sulfide/CSE system in the SHR smooth muscle cells.J Appl Clin Pediatr,2006,21(3):140-141

Gaseous signal molecule hydrogen sulfide and penile erection / 第二军医大学学报

Endogenous hydrogen sulfide is the third gaseous signal molecule after nitric oxide and carbon monoxide;it is synthesized through cystathionine-?-synthase and cystathionine-?-cleavage pathway.Hydrogen sulfide can directly react with the KATP channel,reduce extracellular Ca2+ influx,and work together with testosterone,nitric oxide,carbon monoxide,relaxing corpus cavernosum smooth muscle and improving diastolic function of blood vessels.It can also inhibit vascular smooth muscle cell proliferation,promote apoptosis,and improve vascular remodeling.Therefore,in-depth study of H2S in the regulating penile erection can provide a new way for the treatment of erectile dysfunction.