Document Detail


G2A plays proinflammatory roles in human keratinocytes under oxidative stress as a receptor for 9-hydroxyoctadecadienoic acid.
MedLine Citation:
PMID:  18034171     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
G2A is a stress-inducible G protein-coupled receptor for oxidized free fatty acids, such as 9-hydroxyoctadecadienoic acid (HODE). As skin is routinely and pathologically exposed to many oxidative stresses such as UV radiation, chemical agents, and inflammation that might induce both G2A expression and production of G2A ligands, we examined G2A function in human keratinocytes. G2A was expressed in human epidermis, normal human epidermal keratinocytes (NHEK), and an immortalized human keratinocyte cell line (HaCaT). 9(S)-HODE evoked intracellular calcium mobilization and secretion of cytokines, including IL-6, IL-8, and GM-CSF in NHEK cells. These responses became prominent in HaCaT cells by overexpression of G2A. 9(S)-HODE inhibited proliferation of NHEK cells by suppressing DNA synthesis and arresting the cell cycle in the G0/1-phase. On the other hand, 13(S)-HODE, another major oxidative product from linoleate, showed little or no effect on either cytokine secretion or on proliferation in NHEK cells. A small interfering RNA designed to downregulate G2A caused suppression of 9(S)-HODE-induced inhibitory effects on proliferation of NHEK cells. UVB and H(2)O(2) induced G2A expression and caused oxidation of linoleate to produce 9-HODE in HaCaT cells. These results suggest that 9-HODE-G2A signaling plays proinflammatory roles in skin under oxidative conditions.
Authors:
Tomoyasu Hattori; Hideru Obinata; Ai Ogawa; Mikiko Kishi; Kazuaki Tatei; Osamu Ishikawa; Takashi Izumi
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2007-11-22
Journal Detail:
Title:  The Journal of investigative dermatology     Volume:  128     ISSN:  1523-1747     ISO Abbreviation:  J. Invest. Dermatol.     Publication Date:  2008 May 
Date Detail:
Created Date:  2008-04-14     Completed Date:  2008-05-19     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0426720     Medline TA:  J Invest Dermatol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1123-33     Citation Subset:  IM    
Affiliation:
Department of Molecular Biochemistry, Gunma University Graduate School of Medicine, Maebashi, Gunma, Japan.
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Descriptor/Qualifier:
Calcium / metabolism
Cell Cycle Proteins / genetics,  metabolism*
Cell Division / drug effects,  physiology
Cells, Cultured
Cytokines / metabolism,  secretion
Dermatitis / metabolism*
Epidermis / cytology
G0 Phase / drug effects,  physiology
G1 Phase / drug effects,  physiology
Gene Expression / drug effects,  immunology,  radiation effects
Humans
Hydrogen Peroxide / pharmacology
Keratinocytes / cytology,  immunology*,  metabolism
Linoleic Acids, Conjugated / metabolism*,  pharmacology
Oxidants / pharmacology
Oxidative Stress / immunology*
RNA, Messenger / metabolism
Receptors, G-Protein-Coupled / genetics,  metabolism*
Signal Transduction / drug effects,  immunology
Ultraviolet Rays
Chemical
Reg. No./Substance:
0/Cell Cycle Proteins; 0/Cytokines; 0/G2A receptor; 0/Linoleic Acids, Conjugated; 0/Oxidants; 0/RNA, Messenger; 0/Receptors, G-Protein-Coupled; 15514-85-9/9-hydroxy-10,12-octadecadienoic acid; 7440-70-2/Calcium; 7722-84-1/Hydrogen Peroxide

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


Previous Document:  Congenital disorders of glycosylation type Ia as a cause of mirror syndrome.
Next Document:  The impact of architectural design upon the environmental sound and light exposure of neonates who r...