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Activation of p38 MAPK induced peroxynitrite generation in LPS plus IFN-gamma-stimulated rat primary astrocytes via activation of iNOS and NADPH oxidase.
Neurochem Int. 2008 May; 52(6):1188-97.NI

Abstract

We have shown that immunostimulated astrocytes produce excess nitric oxide (NO) and eventually peroxynitrite (ONOO(-)) that was closely associated with the glucose deprivation-potentiated death of astrocytes. The present study shows that activated p38 MAPK regulates ONOO(-) generation from lipopolysaccharide (LPS) plus interferon-gamma (IFN-gamma)-stimulated astrocytes. LPS+IFN-gamma-induced p38 MAPK activation and ONOO(-) generation were attenuated by SB203580 or SKF-86002, specific inhibitors of p38 MAPK. ONOO(-) generation was blocked by NADPH oxidase inhibitor, diphenyleneiodonium chloride, and nitric oxide synthase (NOS) inhibitor, N omega-nitro-L-arginine methyl ester, suggesting both enzymes are involved in ONOO(-) generation. Inhibition of p38 MAPK suppressed LPS+IFN-gamma-induced NO production through down-regulating inducible form of NOS expression. It also suppressed LPS+IFN-gamma-induced NADPH oxidase activation and eventually, the inducible form of superoxide production. Transfection with dominant negative vector of p38 alpha reduced LPS+IFN-gamma-induced ONOO(-) generation through blocking both iNOS-derived NO production and NADPH oxidase-derived O2(-) production. Our results suggest that activated p38 MAPK may serve as a potential signaling molecule in ONOO(-) generation through dual regulatory mechanisms, involving iNOS induction and NADPH oxidase activation.

Authors+Show Affiliations

Department of Pharmacology, College of Pharmacy, Seoul National University, San 56-1, Shinlim-Dong, Kwanak-Gu, Seoul 151-742, Republic of Korea.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

18289732

Citation

Yoo, Byoung Kwon, et al. "Activation of P38 MAPK Induced Peroxynitrite Generation in LPS Plus IFN-gamma-stimulated Rat Primary Astrocytes Via Activation of iNOS and NADPH Oxidase." Neurochemistry International, vol. 52, no. 6, 2008, pp. 1188-97.
Yoo BK, Choi JW, Shin CY, et al. Activation of p38 MAPK induced peroxynitrite generation in LPS plus IFN-gamma-stimulated rat primary astrocytes via activation of iNOS and NADPH oxidase. Neurochem Int. 2008;52(6):1188-97.
Yoo, B. K., Choi, J. W., Shin, C. Y., Jeon, S. J., Park, S. J., Cheong, J. H., Han, S. Y., Ryu, J. R., Song, M. R., & Ko, K. H. (2008). Activation of p38 MAPK induced peroxynitrite generation in LPS plus IFN-gamma-stimulated rat primary astrocytes via activation of iNOS and NADPH oxidase. Neurochemistry International, 52(6), 1188-97. https://doi.org/10.1016/j.neuint.2007.12.009
Yoo BK, et al. Activation of P38 MAPK Induced Peroxynitrite Generation in LPS Plus IFN-gamma-stimulated Rat Primary Astrocytes Via Activation of iNOS and NADPH Oxidase. Neurochem Int. 2008;52(6):1188-97. PubMed PMID: 18289732.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Activation of p38 MAPK induced peroxynitrite generation in LPS plus IFN-gamma-stimulated rat primary astrocytes via activation of iNOS and NADPH oxidase. AU - Yoo,Byoung Kwon, AU - Choi,Ji Woong, AU - Shin,Chan Young, AU - Jeon,Se Jin, AU - Park,Seo Jin, AU - Cheong,Jae Hoon, AU - Han,Sun Young, AU - Ryu,Jae Ryun, AU - Song,Mi Ryoung, AU - Ko,Kwang Ho, Y1 - 2007/12/27/ PY - 2007/09/11/received PY - 2007/12/10/revised PY - 2007/12/14/accepted PY - 2008/2/22/pubmed PY - 2008/7/29/medline PY - 2008/2/22/entrez SP - 1188 EP - 97 JF - Neurochemistry international JO - Neurochem Int VL - 52 IS - 6 N2 - We have shown that immunostimulated astrocytes produce excess nitric oxide (NO) and eventually peroxynitrite (ONOO(-)) that was closely associated with the glucose deprivation-potentiated death of astrocytes. The present study shows that activated p38 MAPK regulates ONOO(-) generation from lipopolysaccharide (LPS) plus interferon-gamma (IFN-gamma)-stimulated astrocytes. LPS+IFN-gamma-induced p38 MAPK activation and ONOO(-) generation were attenuated by SB203580 or SKF-86002, specific inhibitors of p38 MAPK. ONOO(-) generation was blocked by NADPH oxidase inhibitor, diphenyleneiodonium chloride, and nitric oxide synthase (NOS) inhibitor, N omega-nitro-L-arginine methyl ester, suggesting both enzymes are involved in ONOO(-) generation. Inhibition of p38 MAPK suppressed LPS+IFN-gamma-induced NO production through down-regulating inducible form of NOS expression. It also suppressed LPS+IFN-gamma-induced NADPH oxidase activation and eventually, the inducible form of superoxide production. Transfection with dominant negative vector of p38 alpha reduced LPS+IFN-gamma-induced ONOO(-) generation through blocking both iNOS-derived NO production and NADPH oxidase-derived O2(-) production. Our results suggest that activated p38 MAPK may serve as a potential signaling molecule in ONOO(-) generation through dual regulatory mechanisms, involving iNOS induction and NADPH oxidase activation. SN - 0197-0186 UR - https://www.unboundmedicine.com/medline/citation/18289732/Activation_of_p38_MAPK_induced_peroxynitrite_generation_in_LPS_plus_IFN_gamma_stimulated_rat_primary_astrocytes_via_activation_of_iNOS_and_NADPH_oxidase_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0197-0186(07)00337-3 DB - PRIME DP - Unbound Medicine ER -