Biliverdin reductase is heat resistant and coexpressed with constitutive and heat shock forms of heme oxygenase in brain.
Two heme oxygenase (HO) isozymes--HO-1, which is a heat shock protein (HSP32), and HO-2--catalyze the isomer-specific production of biliverdin IX alpha and carbon monoxide. The latter has the potential of functioning as a neurotransmitter, whereas the reduced form of biliverdin, bilirubin, has potent antioxidant activity. Formation of bilirubin is catalyzed by biliverdin reductase (BVR). The reductase is a unique enzyme in being dual pyridine nucleotide and dual pH dependent. Here, we show that the reductase is resistant to thermal stress at both the protein and message level. We further demonstrate that the reductase is coexpressed in cells that display HO-1 and/or HO-2 under normal conditions, as well as in regions and cell types that have the potential to express heat shock-inducible HO-1 protein. Exposure of male rats to 42 degrees C for 20 min did not decrease brain BVR activity, but caused a slight increase in NADPH- and NADH-dependent activities at 1 and 6 h following hyperthermia. High levels of the approximately 1.5-kb BVR mRNA were detected in control brain; it too displayed thermal tolerance. Similarly, the pattern of multiplicity of net charge variants of the enzyme purified from brain of heat-shocked rats did not differ from the control pattern. Immunochemical localization of BVR protein in normal brain correlated well with the presence of HO-1 and/or HO-2 throughout the forebrain, diencephalon, cerebellum, and brainstem regions. There were select neuronal and nonneuronal cells in the substantia nigra and cerebellum that did express the reductase under normal conditions, wherein no HO isozymes could be detected.(ABSTRACT TRUNCATED AT 250 WORDS)
Ewing
J F
JF
Department of Biophysics, University of Rochester School of Medicine, New York 14642.
Weber
C M
CM
Maines
M D
MD
D000818:Animals; D001921:Brain / Q000166:cytology / Q000378:metabolism*; D004355:Drug Stability; D006419:Heme Oxygenase (Decyclizing) / Q000737:chemistry / Q000378:metabolism*; D006358:Hot Temperature; D007527:Isoenzymes / Q000378:metabolism; D008297:Male; D010088:Oxidoreductases / Q000737:chemistry* / Q000378:metabolism*; D044925:Oxidoreductases Acting on CH-CH Group Donors; D051381:Rats; D017207:Rats, Sprague-Dawley; D012016:Reference Values; D012769:Shock / Q000378:metabolism*; D014018:Tissue Distribution
D007527:Isoenzymes; D010088:Oxidoreductases; D006419:Heme Oxygenase (Decyclizing); D044925:Oxidoreductases Acting on CH-CH Group Donors; C019789:biliverdin reductase