NDLI: Significance of ERK nitration in portal hypertensive gastropathy and its therapeutic implications.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Kinjo, Nao Kawanaka, Hirofumi Akahoshi, Tomohiko Yamaguchi, Shohei Yoshida, Daisuke Anegawa, Go Konishi, Kozo Tomikawa, Morimasa Tanoue, Kazuo Tarnawski, Andrzej Hashizume, Makoto Maehara, Yoshihiko
Description	Country affiliation: Japan Author Affiliation: Kinjo N ( Dept. of Surgery and Science, Kyushu University, Higashi-ku, Fukuoka 812-8582, Japan. naokinjo@surg2.med.kyushu-u.ac.jp)
Abstract	Portal hypertensive (PHT) gastric mucosa increases susceptibility to injury and delayed mucosal healing. It is possible that nitration of ERK by peroxynitrite might alter MAPK (ERK) signaling in PHT gastric mucosa, leading to delayed mucosal healing, since excessive nitric oxide production is implicated in PHT gastric mucosa and MAPK (ERK) signaling induces cell proliferation and leads to gastric mucosal healing in response to injury. Portal hypertension was produced by staged portal vein ligation, and sham-operation (SO) rats served as controls. Lipid peroxide (LPO) and nitrotyrosine increased significantly in PHT gastric mucosa compared with SO rats. ERK activation was impaired in PHT gastric mucosa in response to ethanol injury, whereas no significant difference in the phosphorylation of MEK, an upstream molecule of ERK, was seen between the two groups. The nitration of ERK by peroxynitrite, as detected by the coimmunoprecipitation of ERK and nitrotyrosine, was significantly enhanced in PHT gastric mucosa. Administration of rebamipide, a gastroprotective drug that acts as an oxygen-derived free radical scavenger, significantly decreased LPO and nitrotyrosine as well as the nitration of ERK by peroxynitrite in PHT gastric mucosa, therefore normalizing ERK activation and restoring the gastric mucosal healing response to ethanol injury. Enhanced nitration of ERK by peroxynitrite is involved in the impaired MAPK (ERK) signaling in PHT gastric mucosa. These findings demonstrate a new molecular mechanism in which PHT gastric mucosa is predisposed to injury and impaired healing.
File Format	HTM / HTML
ISSN	01931857
Issue Number	5
Volume Number	295
e-ISSN	15221547
Journal	AJP: Gastrointestinal and Liver Physiology
Language	English
Publisher	American Physiological Society
Publisher Date	2008-11-01
Publisher Place	United States
Access Restriction	Subscribed
Subject Keyword	Discipline Physiology Discipline Gastroenterology Extracellular Signal-regulated Map Kinases Metabolism Liver Cirrhosis Complications Stomach Diseases Drug Therapy Alanine Analogs & Derivatives Pharmacology Animals Enzyme Inhibitors Ethanol Toxicity Gastric Mucosa Drug Effects Map Kinase Kinase Kinases Nitrates Oxidative Stress Peroxynitrous Acid Quinolones Rats Rats, Sprague-dawley Signal Transduction Physiology Tyrosine Journal Article
Content Type	Text
Resource Type	Article
Subject	Hepatology Physiology Physiology (medical) Gastroenterology

Sl.	Authority	Responsibilities	Communication Details
1	Ministry of Education (GoI), Department of Higher Education	Sanctioning Authority	https://www.education.gov.in/ict-initiatives
2	Indian Institute of Technology Kharagpur	Host Institute of the Project: The host institute of the project is responsible for providing infrastructure support and hosting the project	https://www.iitkgp.ac.in
3	National Digital Library of India Office, Indian Institute of Technology Kharagpur	The administrative and infrastructural headquarters of the project	Dr. B. Sutradhar bsutra@ndl.gov.in
4	Project PI / Joint PI	Principal Investigator and Joint Principal Investigators of the project	Dr. B. Sutradhar bsutra@ndl.gov.in Prof. Saswat Chakrabarti will be added soon
5	Website/Portal (Helpdesk)	Queries regarding NDLI and its services	support@ndl.gov.in
6	Contents and Copyright Issues	Queries related to content curation and copyright issues	content@ndl.gov.in
7	National Digital Library of India Club (NDLI Club)	Queries related to NDLI Club formation, support, user awareness program, seminar/symposium, collaboration, social media, promotion, and outreach	clubsupport@ndl.gov.in
8	Digital Preservation Centre (DPC)	Assistance with digitizing and archiving copyright-free printed books	dpc@ndl.gov.in
9	IDR Setup or Support	Queries related to establishment and support of Institutional Digital Repository (IDR) and IDR workshops	idr@ndl.gov.in