Induction of heart heme oxygenase-1 (HSP32) by hyperthermia: possible role in stress-mediated elevation of cyclic 3':5'-guanosine monophosphate.
Presently we have investigated the carbon monoxide generating capacity of the cardiovascular system under normal and stress conditions by examining the microsomal heme oxygenase system at the transcript, protein and activity levels; and have assessed response of heart nitric oxide (NO) synthase activity and cyclic GMP levels to stress. Heme oxygenase (HO) isozymes, HO-1 (HSP32) and HO-2, catalyze the rate limiting step in the only known pathway in eukaryotes for the generation of the potential cellular message, carbon monoxide, and the antioxidant, bilirubin. We show expression of HO-1 and HO-2 at both the transcription and protein levels under normal conditions in the heart and descending aorta, and demonstrate the sensitivity of only the HO-1 isozyme to heat stress in these tissues. The ratio of the two HO-2 homologous transcripts (approximately 1.9 and 1.3 Kb) present in the atrium, ventricles and descending aorta and their levels were not altered by hyperthermia (42 degrees C, 20 min) when measured 1 or 6 hr after treatment. In contrast, hyperthermia caused a rapid, robust and coordinate increase of approximately 10- to 32-fold in the approximately 1.8-Kb HO-1 mRNA in these tissues when measured 1-hr post-treatment. Hyperthermia also caused a significant increase in both HO-1 protein and heme degradation capacity in the heart. Furthermore, the induction of HO-1 protein in the heart was accompanied by a significant elevation in tissue cyclic GMP level first detected 1-hr post-treatment and was sustained 6 hr after heat shock.(ABSTRACT TRUNCATED AT 250 WORDS)
Ewing
J F
JF
University of Rochester School of Medicine, Department of Biophysics, New York.
Raju
V S
VS
Maines
M D
MD
D000594:Amino Acid Oxidoreductases / Q000378:metabolism; D000818:Animals; D006152:Cyclic GMP / Q000096:biosynthesis*; D004790:Enzyme Induction; D005334:Fever / Q000378:metabolism*; D006360:Heat-Shock Proteins / Q000096:biosynthesis*; D006419:Heme Oxygenase (Decyclizing) / Q000096:biosynthesis* / Q000235:genetics; D007527:Isoenzymes / Q000096:biosynthesis*; D008297:Male; D009206:Myocardium / Q000201:enzymology*; D019001:Nitric Oxide Synthase; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley
D006360:Heat-Shock Proteins; D007527:Isoenzymes; D012333:RNA, Messenger; D019001:Nitric Oxide Synthase; D006419:Heme Oxygenase (Decyclizing); D000594:Amino Acid Oxidoreductases; D006152:Cyclic GMP