Research Center, UMDNJ-NJ Dental School, University of Medicine and Dentistry of New Jersey, Newark, NJ 07103-2400, USA.
Inflammopharmacology. 2011 Apr;19(2):89-97. doi: 10.1007/s10787-011-0078-4. Epub 2011 Jan 29.
Loss of mucus coat integrity and the impairment in its mucin component as well as the disturbance in nitric oxide (NO) generation are well-recognized features of gastric disease associated with H. pylori infection. As ghrelin plays a major role in the regulation of nitric oxide synthase system, we investigated the influence of this hormone on H. pylori LPS-induced interference with gastric mucin synthesis. The results revealed that the LPS-induced impairment in mucin synthesis and accompanied induction in inducible nitric oxide synthase (iNOS) expression, were associated with the suppression in Akt kinase activity and the impairment in constitutive nitric oxide synthase (cNOS) phosphorylation. The LPS effect on Akt inactivation was manifested in the kinase protein S-nitrosylation and a decrease in its phosphorylation at Ser(473). Further, we show that the countering effect of ghrelin, on the LPS-induced impairment in mucin synthesis was reflected in the suppression of iNOS and the increase in Akt activation, associated with the loss in S-nitrosylation and the increase in phosphorylation, as well as cNOS activation through phosphorylation. Our findings demonstrate that up-regulation in iNOS with H. pylori infection and subsequent Akt kinase inactivation through S-nitrosylation exerts the detrimental effect on the processes dependent on Akt activation, including that of cNOS activation and mucin synthesis. We also show that ghrelin protection against H. pylori-induced impairment in mucin synthesis is intimately linked to the events of Akt activation and reflected in a decrease in the kinase S-nitrosylation and the increase in its phosphorylation.
黏液层完整性的丧失及其黏蛋白成分的损伤以及一氧化氮（NO）生成的紊乱是与 H. pylori 感染相关的胃部疾病的公认特征。由于生长激素释放肽在调节一氧化氮合酶系统中起主要作用，我们研究了这种激素对 H. pylori LPS 诱导的胃黏液合成干扰的影响。结果表明，LPS 诱导的黏液合成损伤以及伴随的诱导型一氧化氮合酶（iNOS）表达增加与 Akt 激酶活性的抑制和组成型一氧化氮合酶（cNOS）磷酸化的损伤有关。LPS 对 Akt 失活的影响表现为激酶蛋白 S-亚硝基化和 Ser(473)磷酸化减少。此外，我们表明，ghrelin 对 LPS 诱导的黏液合成损伤的拮抗作用反映在 iNOS 的抑制和 Akt 激活的增加，与 S-亚硝基化的丧失和磷酸化的增加以及通过磷酸化的 cNOS 激活有关。我们的研究结果表明，H. pylori 感染引起的 iNOS 上调以及随后通过 S-亚硝基化导致 Akt 激酶失活对依赖 Akt 激活的过程产生有害影响，包括 cNOS 激活和黏液合成。我们还表明，ghrelin 对 H. pylori 诱导的黏液合成损伤的保护作用与 Akt 激活的事件密切相关，并反映在激酶 S-亚硝基化的减少和磷酸化的增加。
