EXPRESSION OF HEME OXYGENASE ISOZYME MESSENGER-RNAS IN THE HUMAN BRAIN AND INDUCTION OF HEME OXYGENASE-1 BY NITRIC-OXIDE DONORS

Heme oxygenase is an essential enzyme in the heme catabolism that prod uces carbon monoxide (CO). This study was designed to examine the expr ession of two heme oxygenase isozyme mRNAs in the human brain and to e xplore the involvement of nitric oxide (NO) and various neuropeptides in the regulation of their expression. Northern blot analysis showed t he expression of heme oxygenase-1 and heme oxygenase-2 mRNAs in every region of the brain examined, with the highest levels found in the fro ntal cortex, temporal cortex, occipital cortex, and hypothalamus. In a human glioblastoma cell line, T98G, treatment with any of three types of NO donors-sodium nitroprusside, 3-morpholinosydnonimine, and S-nit roso-L-glutathione-caused a significant increase in the levels of heme oxygenase-1 mRNA but not in the levels of heme oxygenase-2 and heat-s hock protein 70 mRNAs. Sodium nitroprusside increased the levels of he me oxygenase-1 protein but not the levels of heat-shock protein 70 in T98G cells. The increase in content of heme oxygenase-1 mRNA caused by sodium nitroprusside was completely abolished by the treatment with a ctinomycin D. On the other hand, the levels of heme oxygenase isozyme mRNAs were not noticeably changed in T98G cells following the treatmen t with 8-bromo cyclic GMP, sodium nitrite, or various neuropeptides, s uch as calcitonin gene-related peptide, endothelin-1, and corticotropi n-releasing hormone. The present study has shown the expression profil es of heme oxygenase-1 and -2 mRNAs in the human brain and the inducti on of heme oxygenase-1 mRNA caused by NO donors in T98G cells. These f indings raise a possibility that the CO/heme oxygenase system may func tion in concert with the NO/NO synthase system in the brain.