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Volume 200 (2003)
- Issue 4 Pages 167-
- Issue 3 Pages 111-
- Issue 2 Pages 67-
- Issue 1 Pages 1-
Volume 200, Issue 4
August
Displaying 1-5 of 5 articles from this issue
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Invited Review
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Shigeki Shibahara2003 Volume 200 Issue 4 Pages 167-186
Published: 2003
Released on J-STAGE: September 08, 2004
JOURNAL FREE ACCESSHeme must be synthesized and degraded within an individual nucleated cell. Heme degradation is catalyzed by the two isozymes of heme oxygenase, heme oxygenase-1 (HO-1) and HO-2, eventually yielding biliverdin-/bilirubin, CO, and iron. These products possess important physiological roles but are potentially toxic to cells. Characteristically, human HO-1 contains no Cys residues, whereas HO-2 contains the potential heme-binding motifs of the Cys-Pro dipeptide. Expression of HO-1 is inducible or repressible, depending on cell types or cellular microenvironments, but expression levels of HO-2 are fairly constant. Thus, the main regulation of heme catabolism is a problem of the balance between induction and repression of HO-1. Notably, HO-1 expression is induced by heme in all mammalian cells examined, but is repressed by hypoxia in certain types of cultured human cells. The recent discovery of Bach1 as a heme-regulated and hypoxia-inducible repressor for transcription of the HO-I gene has provided a missing link in the feedback control of heme catabolism. On the other hand, the human HO-1 gene promoter contains the (GT)n repeat polymorphism and a single nucleotide polymorphism (−413A→T), both of which may contribute to fine-tuning of the transcription. Importantly, long (GT)n alleles are associated with susceptibility to smoking-induced emphysema or coronary artery disease, but may provide with resistance to cerebral malaria. The latter finding suggests a novel therapeutic strategy with inhibitors of HO-1 for the treatment of cerebral malaria. We discuss the potential regulatory role of Bach1 and HO-2 in heme catabolism and update the understanding of the regulation of HO-1 expression.View full abstractDownload PDF (600K)
Regular Contributions
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Koji Yamashita, Tadaatsu Imaizumi, Masaharu Hatakeyama, Wakako Tamo, D ...2003 Volume 200 Issue 4 Pages 187-194
Published: 2003
Released on J-STAGE: September 08, 2004
JOURNAL FREE ACCESSCX3CL1-/fractalkine is a chemokine with a unique CX3C motif. Hypoxia mediates the expression of various genes, such as vascular endothelial growth factor (VEGF), cyclooxygenase-2, and plasminogen-activator inhibitor-1, in vascular endothelial cells. We studied the eect of hypoxia on the expression of fractalkine induced by interferon-γ (IFN-γ) in endothelial cells. Human umbilical vein endothelial cells were cultured, and the stimulation of the cells with IFN-γ was found to induce the expression of fractalkine. Hypoxia inhibited the expression of fractalkine mRNA and protein by IFN-γ, and this eect was observed with concomitant increase in VEGF expression. Desferrioxamine, an iron chelator that mimics hypoxia in vitro, also inhibited the fractalkine production induced by IFN-γ. Hypoxia did not aect the degradation of fractalkine mRNA. The inhibition of fractalkine expression by hypoxia was reversed on returning the cultures to reoxygenation condition. Inhibition of IFN-induced fractalkine expression by hypoxia was not aected by the presence of a radical scavenger, N-acetyl-L-cysteine, and the involvement of reactive oxygen species may be excluded. Inhibition of fractalkine expression by hypoxia may be involved in the pathophysiology of ischemic diseases.View full abstractDownload PDF (178K) -
Keiji Tabuchi, Tomohumi Hoshino, Hidekazu Murashita, Keiko Oikawa, Isa ...2003 Volume 200 Issue 4 Pages 195-202
Published: 2003
Released on J-STAGE: September 08, 2004
JOURNAL FREE ACCESSWe investigated effects of poly(ADP-ribose) synthetase (PARS) inhibitors on acoustic trauma. Albino guinea pigs were intravenously given 3-aminobenzamide, nicotinamide or 3-aminobenzoic acid (an inactive analog of 3-aminobenzamide) just prior to exposure to a 2 kHz pure tone of 120 dB sound pressure level (SPL) for 10 minutes. The threshold of the compound action potential (CAP) and the amplitude of distortion-product otoacoustic emissions (DPOAEs) were measured before and 4 hours after the acoustic overexposure. Statistically signicant decreases in the CAP threshold shifts and signicant increases in the DPOAE amplitudes were observed 4 hours after the acoustic overexposure in the animals treated with 3-aminobenzamide or nicotinamide, whereas 3-aminobenzoic acid did not exert any protective eect. These results strongly suggest that excessive activation of PARS is involved in generation of the acoustic trauma.View full abstractDownload PDF (133K) -
Volkan Etus, Tuncay Altug, Ahmet Belce, Savas Ceylan2003 Volume 200 Issue 4 Pages 203-209
Published: 2003
Released on J-STAGE: September 08, 2004
JOURNAL FREE ACCESSHydrocephalus causes damage to periventricular white matter at least in part through chronic ischemia. Emphasizing the periventricular ischemia/hypoxia in hydrocephalus, various authors indicated the secondary biochemical impairment and oxidative damage in experimentally induced and congenital hydrocephalic rat brain. (−)-Epigallocatechin gallate (EGCG), the main constituent of green tea polyphenols, has been shown to be of some protective value in various models of neurological injury as a free oxygen radical scavenger. In the present study the effects of EGCG were examined on the periventricular oxidative damage in experimental childhood-onset hydrocephalus. Hydrocephalus was induced in 3 weeks-old rat pups by kaolin injection into the cisterna magna. A single daily dose of 50 mg-/kg of EGCG injected into the peritoneum of the rats for 15 days signicantly reduced periventricular white matter malondialdehyde levels when compared to non-treated hydrocephalic animals. Our results indicate that EGCG may have a protective effect against periventricular white matter oxidative damage in hydrocephalus induced infantile rats.View full abstractDownload PDF (154K) -
Maki Takata-Yahiro, Yoshito Fujii, Jorge Fraga Nodarse, Mohammed Rafiq ...2003 Volume 200 Issue 4 Pages 211-229
Published: 2003
Released on J-STAGE: September 08, 2004
JOURNAL FREE ACCESSMismatched or damaged base pairs in DNA are mutagenic and both eukaryotes and prokaryotes have a series of repair systems that decrease a spontaneous mutation rate. All exocyclic amino groups of cytosine(C), adenine(A), and guanine(G) contribute to hydrogen bonds for base pairing. High temperature and oxidative stresses increase the deamination of these bases and methylated C. These deaminated sites would be initially recognized by components of DNA repair system. We discovered a novel G/thymine(T)-mismatch binding protein (nGTBP) that bound, with high affinity, to a minimal 14-mer DNA heteroduplex with a strict 5’-TRTGNB-3’ sequence (R for purine, N for any bases, and B for “not A,” namely for C, G, or T ). This italicized G position mismatched with T could be replaced by hypoxanthine, the deaminated A. The nGTBP, however, barely recognized DNA duplexes individually containing 8-oxo-G, thymine glycol, and 5-methylcytosine.View full abstractDownload PDF (908K)
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