التفاصيل البيبلوغرافية
العنوان:
Distinct involvement of NF-kappaB and p38 mitogen-activated protein kinase pathways in serum deprivation-mediated stimulation of inducible nitric oxide synthase and its inhibition by 4-hydroxynonenal
المؤلفون:
Michio Yajima , Izumi Nakashima , Jianghong Wu , Hidetsugu Murakami , Naohisa Ishikawa , Masataka Itoigawa , Masashi Kato , Wei Liu
المصدر:
Journal of cellular biochemistry . 83(2)
سنة النشر:
2001
مصطلحات موضوعية:
Pyridines , Nitric Oxide Synthase Type II , IκB kinase , Mitogen-activated protein kinase kinase , Nitric Oxide , Biochemistry , p38 Mitogen-Activated Protein Kinases , Culture Media, Serum-Free , MAP2K7 , Mice , TANK-binding kinase 1 , Animals , ASK1 , Phosphorylation , Molecular Biology , MAPK14 , Aldehydes , MAP kinase kinase kinase , Akt/PKB signaling pathway , Chemistry , Macrophages , Imidazoles , NF-kappa B , Cell Biology , Molecular biology , I-kappa B Proteins , Mitogen-Activated Protein Kinases , Nitric Oxide Synthase , Signal Transduction
الوصف:
Cytokine-induced expression of inducible nitric oxide synthase (iNOS) and concomitant production of nitric oxide (NO) involve activation of mitogen-activated protein (MAP) kinases and are in most cases mediated by the transcription factor NF-κB. We investigated the role of p38 MAP kinase activation and IκB phosphorylation in iNOS expression in a novel iNOS-inducing model in mouse macrophages. Deprivation of serum from the culture medium of RAW 264.7 cells up-regulated iNOS and NO production, which were inhibited by 4-hydroxy-2-nonenal (HNE), a component of oxidatively modified low-density lipoprotein (oxLDL). Serum withdrawal induced phosphorylation of Akt, IκB, and p38 MAP kinase. Pretreatment with the potent PI3 kinase inhibitor wortmannin, the NF-κB inhibitor PDTC or the specific p38 MAP kinase inhibitor SB203580 each partially attenuated the induction of iNOS and NO production, demonstrating that both p38 activation and IκB phosphorylation are required for iNOS expression. SB203580, however, did not prevent the phosphorylation of Akt and IκB, suggesting that the p38 MAP kinase signal contributes to iNOS gene expression through an IκB-phosphorylation-independent pathway. HNE, which markedly inhibited iNOS expression and NO production, prevented the serum withdrawal-triggered IκB phosphorylation but not that of Akt or p38 MAP kinase. A high concentration of HNE stimulated dephosphorylation of IκB but promoted activation of p38 MAP kinase. Taken together, these results suggest that NF-κB and p38 MAP kinase lie in separate signal pathways for serum deprivation-stimulated iNOS expression and NO production. HNE selectively suppresses the former pathway, targeting a site downstream of Akt. J. Cell. Biochem. 83: 271–280, 2001. © 2001 Wiley-Liss, Inc.
تدمد:
0730-2312
URL الوصول:
https://explore.openaire.eu/search/publication?articleId=doi_dedup___::d816e1e1c2207be0290936daa23ae442 https://pubmed.ncbi.nlm.nih.gov/11573244
حقوق:
CLOSED
رقم الأكسشن:
edsair.doi.dedup.....d816e1e1c2207be0290936daa23ae442
قاعدة البيانات:
OpenAIRE
