Normal and heat-induced patterns of expression of heme oxygenase-1 (HSP32) in rat brain: hyperthermia causes rapid induction of mRNA and protein.
Most cells possess a variety of mechanisms, such as high levels of glutathione, that guard against cytotoxic free radicals, which are suspected in the etiology of various neurological deficits. Neurons, however, are deficient in this antioxidant source. The list of other potent antioxidants includes the bile pigments biliverdin and bilirubin. Heme oxygenase (HO) isozymes, HO-1 (HSP32) and HO-2, catalyze the rate-limiting step in the only biological pathway by which bile pigments are produced. In this study, heat shock is identified as the only stimulus reported to date that can alter expression in brain HO-1 of protein and mRNA in vivo. Using a HO-1 cDNA probe, we examined the level of HO-1 mRNA in normal rat brain and in brain 1 and 6 h following heat shock. Exposure of male rats to 42 degrees C for 20 min caused a 20-fold increase in brain HO-1 1.8-kb mRNA within 1 h after treatment. Quantification of brain HO-1 protein by HO-1 radioimmunoassay revealed a fourfold increase at 6 h posttreatment. In normal brain, HO-1 protein was sparsely expressed in few select neuronal and nonneuronal cell populations in forebrain, diencephalon, cerebellum, and brainstem regions. Six hours following heat shock, an intense increase in HO-1 protein in glia throughout the brain, ependyma lining the ventricles of the brain, paraventricular nucleus, Purkinje cell layer of the cerebellum, and cochlear nucleus of brainstem was observed. We suggest that increases in HO-1 transcript and protein reflect a means to elevate levels of antioxidants in cells with compromised defense mechanisms caused by stress.
Ewing
J F
JF
Department of Biophysics, University of Rochester Medical Center, New York 14642.
Haber
S N
SN
Maines
M D
MD
D000818:Animals; D001483:Base Sequence; D001921:Brain / Q000378:metabolism*; D005334:Fever / Q000378:metabolism*; D006419:Heme Oxygenase (Decyclizing) / Q000235:genetics / Q000378:metabolism*; D006358:Hot Temperature; D007150:Immunohistochemistry; D008969:Molecular Sequence Data; D009474:Neurons / Q000378:metabolism; D015345:Oligonucleotide Probes / Q000235:genetics; D012333:RNA, Messenger / Q000378:metabolism*; D051381:Rats; D012016:Reference Values; D013997:Time Factors
D015345:Oligonucleotide Probes; D012333:RNA, Messenger; D006419:Heme Oxygenase (Decyclizing)