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PMID: 2052613 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Rapid induction of heme oxygenase 1 mRNA and protein by hyperthermia in rat brain: heme oxygenase 2 is not a heat shock protein.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 88 ·No. 12 ·1991-06-15 ·Pages 5364-8

Ewing JF, Maines MD

Abstract

Catalytic activity of heme oxygenase (heme, hydrogen-donor:oxygen oxidoreductase, EC 1.14.99.3) isozymes, HO-1 and HO-2, permits production of physiologic isomers of bile pigments. In turn, bile pigments biliverdin and bilirubin are effective antioxidants in biological systems. In the rat brain we have identified only the HO-1 isozyme of heme oxygenase as a heat shock protein and defined hyperthermia as a stimulus that causes an increase in brain HO-1 protein. Exposure of male rats to 42 degrees C for 20 min caused a rapid and marked increase in brain 1.8-kilobase HO-1 mRNA. Specifically, a 33-fold increase in brain HO-1 mRNA was observed within 1 h and sustained for at least 6 h posttreatment. In contrast, the two HO-2 homologous transcripts (1.3 and 1.9 kilobases) did not respond to heat shock; neither the ratio nor the level of the two messages differed from that of the control when measured either at 1, 6, or 24 h after hyperthermia. The induction of a 1.8-kilobase HO-1 mRNA resulted in a pronounced increase in HO-1 protein 6 h after hyperthermia, as detected by both Western immunoblot and RIA. Immunocytochemistry of rat brain showed discrete localization of HO-1-like protein only in neurons of select brain regions. Six hours after heat shock, an intense increase in HO-1-like protein was observed in both Purkinje cells of the cerebellum and epithelial cells lining the cerebral aqueduct of the brain. We suggest that the increase in HO-1 protein, hence increased capacity to form bile pigments, represents a neuronal defense mechanism against heat shock stress.

MeSH Terms
Animals Base Sequence Blotting, Northern Blotting, Western Brain/enzymology Heat-Shock Proteins/chemistry Heme Oxygenase (Decyclizing)/chemistry,genetics Hyperthermia, Induced Immunohistochemistry Isoenzymes/chemistry,genetics Molecular Sequence Data RNA, Messenger/biosynthesis Radioimmunoassay Rats
Chemicals
Heat-Shock Proteins Isoenzymes RNA, Messenger Heme Oxygenase (Decyclizing)
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
Ewing J F
Department of Biophysics, University of Rochester Medical Center, NY 14642.
Maines M D
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Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
DOI
10.1073/pnas.88.12.5364
Published
1991-06-15
Pages
5364-8
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC51873
Subset
IM
Grants
NIEHS NIH HHS · ES01247 · United States
NIEHS NIH HHS · ES03968 · United States
PHS HHS · R3704391 · United States
External Links
PubMed source DOI: 10.1073/pnas.88.12.5364 PMC Full Text View journal details
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