Expression of Heme Oxygenase Isozyme mRNAs in the Human Brain and Induction of Heme Oxygenase‐1 by Nitric Oxide Donors

Abstract

Heme oxygenase is an essential enzyme in the heme catabolism that produces carbon monoxide (CO). This study was designed to examine the expression of two heme oxygenase isozyme mRNAs in the human brain and to explore the involvement of nitric oxide (NO) and various neuropeptides in the regulation of their expression. Northern blot analysis showed the expression of heme oxygenase‐1 and heme oxygenase‐2 mRNAs in every region of the brain examined, with the highest levels found in the frontal 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‐nitroso‐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‐shock protein 70 mRNAs. Sodium nitroprusside increased the levels of heme 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 actinomycin D. On the other hand, the levels of heme oxygenase isozyme mRNAs were not noticeably changed in T98G cells following the treatment with 8‐bromo cyclic GMP, sodium nitrite, or various neuropeptides, such as calcitonin gene‐related peptide, endothelin‐1, and corticotropin‐releasing hormone. The present study has shown the expression profiles of heme oxygenase‐1 and ‐2 mRNAs in the human brain and the induction of heme oxygenase‐1 mRNA caused by NO donors in T98G cells. These findings raise a possibility that the CO/heme oxygenase system may function in concert with the NO/NO synthase system in the brain.

Role of the haeme oxygenase/carbon monoxide pathway in mechanical nociceptor hypersensitivity

“…In contrast to our ®ndings, haeme overload per se has been reported to induce HO-1 (Shibahara, 1988;1994;Takahashi et al, 1996;Anning et al, 1999;Ponka, 1999;Odaka et al, 2000), but this seems not to be the case in the present study since haeme-lysinate counteracted the mechanical nociceptor hypersensitivity produced by IL-1b, which induces HO-1, but not by PGE 2 ; showing that in our experiments a previous induction of HO is necessary for haeme-lysinate eects.…”

Identification and characterization of hypoxia-induced genes in Carassius auratus blastulae embryonic cells using suppression subtractive hybridization

“…HO-1 is also one of the rate-limiting enzymes in heme catabolism and cleaves heme to form biliverdin IXa, carbon monoxide (CO) and iron (Tenhunen et al, 1968;Yoshida and Kikuchi, 1978). Its expression can be strongly induced by a variety of physiological and pathophysiological stimuli in human cells, including heme, heavy metals, inflammatory cytokines, nitric oxide and UV irradiation (Yoshida and Kikuchi, 1978;Keyse and Tyrrell, 1989;Takahashi et al, 1996;Otterbein and Choi, 2000). There are conflicting reports on the response of HO-1 to hypoxic stress in mammals (Nakayama et al, 2000).…”

Heme Degradation and Vascular Injury

“…The expression of HO-1 is triggered by its substrate heme and diverse stress stimuli, including ultraviolet radiation (143), hypoxia (43,85,102), inflammation (1,64,148), heavy metals (3,90,105,134,135), hydrogen peroxide (73,106), and nitric oxide (NO) (47,133,101). According to a study by Alam (124), sodium arsenite, cobalt chloride (92), bacterial lipopolysaccharide (82) and cobalt protoporphyrin (124)] is mediated by AP-1 activation.…”