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PMID: 15194498 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Phosphorylation of p38 MAPK and its downstream targets in SARS coronavirus-infected cells.

Biochemical and biophysical research communications ·Vol. 319 ·No. 4 ·2004-07-09 ·Pages 1228-34

Mizutani T, Fukushi S, Saijo M, Kurane I, Morikawa S

Abstract

Severe acute respiratory syndrome (SARS) has become a global public health emergency. Understanding the molecular mechanisms of SARS-induced cytopathic effects (CPEs) is a rational approach for the prevention of SARS, and an understanding of the cellular stress responses induced by viral infection is important for understanding the CPEs. Polyclonal antibodies, which recognized nucleocapsid (N) and membrane (M) proteins, detected viral N and M proteins in virus-infected Vero E6 cells at least 6 and 12 h post-infection (h.p.i.), respectively. Furthermore, detection of DNA ladder and cleaved caspase-3 in the virus-infected cells at 24h.p.i. indicated that SARS-CoV infection induced apoptotic cell death. Phosphorylation of p38 MAPK was significantly up-regulated at 18 h.p.i. in SARS-CoV-infected cells. The downstream targets of p38 MAPK, MAPKAPK-2, HSP-27, CREB, and eIF4E were phosphorylated in virus-infected cells. The p38 MAPK inhibitor, SB203580, inhibited effectively phosphorylation of HSP-27, CREB, and eIF4E in SARS-CoV-infected cells. However, viral protein synthesis was not affected by treatment of SB203580.

MeSH Terms
Activating Transcription Factor 1 Animals Apoptosis/physiology Cell Line Cyclic AMP Response Element-Binding Protein/metabolism DNA-Binding Proteins Enzyme Activation Eukaryotic Initiation Factor-4E/metabolism Heat-Shock Proteins/metabolism MAP Kinase Signaling System/physiology Mitogen-Activated Protein Kinases/antagonists & inhibitors,metabolism Phosphorylation SARS Virus/metabolism Severe Acute Respiratory Syndrome/metabolism Transcription Factors/metabolism Viral Proteins/metabolism p38 Mitogen-Activated Protein Kinases
Chemicals
Activating Transcription Factor 1 Cyclic AMP Response Element-Binding Protein DNA-Binding Proteins Eukaryotic Initiation Factor-4E Heat-Shock Proteins Transcription Factors Viral Proteins Mitogen-Activated Protein Kinases p38 Mitogen-Activated Protein Kinases
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Mizutani Tetsuya
Special Pathogens Laboratory, Department of Virology 1, National Institute of Infectious Diseases, Gakuen 4-7-1, Musashimurayama, Tokyo 208-0011, Japan. tmizutan@nih.go.jp
Fukushi Shuetsu
Saijo Masayuki
Kurane Ichiro
Morikawa Shigeru
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Article Info
Journal
Biochemical and biophysical research communications
Abbr.
Biochem Biophys Res Commun
ISSN
0006-291X
DOI
10.1016/j.bbrc.2004.05.107
Email
tmizutan@nih.go.jp
Published
2004-07-09
Pages
1228-34
Language
English
Region
United States
NLM ID
0372516
PMCID
PMC7111015
Subset
IM
External Links
PubMed source DOI: 10.1016/j.bbrc.2004.05.107 PMC Full Text View journal details
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