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Volume 114, Issue 5
Displaying 1-7 of 7 articles from this issue
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Kazuhiro OGAWA, Shigeki SHIBAHARA, Hiroyoshi FUJITA1999 Volume 114 Issue 5 Pages 255-264
Published: 1999
Released on J-STAGE: January 30, 2007
JOURNAL FREE ACCESSOne of the most remarkable revolutions during the history of animal kingdom is the adaptation to oxygen, a highly toxic gas produced by plants. Based on the high affinitiy of heme toward oxygen, it has been believed that heme itself and/or hemoprotein should play significant roles in the prosesses of adaptation. Recently, two novel functions of heme and its metabolites were identified; namely, hemoprotein is an oxygen sensor and biliverdin and bilirubin, catabolites of heme, are antioxidants. Thus, heme is a key molecule in the responses to environmental stress, including oxygen. Although activation of hypoxia inducible factor-1, which induces expression of genes encoding erythropoietin and heme oxygenase (HO-1), is generally accepted to be controlled by oxygen sensor, the precise signaling pathway has not yet been well elucidated. Various stresses such as hypoxia are known to activate the HO-1 gene, the key enzyme of heme degradation, resulting in the marked conversion of pro-oxidant (heme) into its antioxidative catabolites. The induction is, therefore, supposed to have protective effects. Recent reports on HO-1 deficiency also support this hypothesis that the activation of the HO-1 gene is one of the most important defense mechanisms against environmental stress.View full abstractDownload PDF (11206K) -
Kazuhito ROKUTAN1999 Volume 114 Issue 5 Pages 265-272
Published: 1999
Released on J-STAGE: January 30, 2007
JOURNAL FREE ACCESSStress response is mediated by a number of stress-related gene products and is crucial for maintenance of homeostasis during and after various cellular stresses. Exposure of rats to restraint and water-immersion stress rapidly and transiently activated heart shock factor 1 (HSF1) and caused rapid HSP70 mRNA expression and HSP70 accumulation in gastric mucosa. Using protein-malnourished, bilateral adrenalectomized, and subdiaphragmatically vagotomized rats, we showed that this heat shock response was regulated by the hypothalamic-pituitary-adrenocortical or the sympathoadrenal systems. Experiments with inhibitors for adrenoceptor subtypes and glucocorticoids suggested that the α1A-adrenergic receptor appeared to mediate the HSP70 induction. The extent of HSP70 induction inversely correlated to the severity of mucosal damage, suggesting an important role of the heat shock response in gastric mucosal defense under conditions of stress. Recently, we found that gastric surface mucous cells possessed a phagocyte NADPH oxidase-like system and secreted abundant superoxide anion (O2-). Helicobactor pylori lipopolysaccharide markedly up-regulated this secretion. The enhanced O2- production activated nuclear factor kappa B by autocrine/paracrine mechanisms, resulting in activation of proinflammatory cytokine gene expressions. These results suggest that surface mucous cells may actively regulate stress responses of Helicobacter pylori-infected gastric mucosa through a phagocyte NADPH oxidase-like activity.View full abstractDownload PDF (7989K) -
Akinori AKAIKE1999 Volume 114 Issue 5 Pages 273-279
Published: 1999
Released on J-STAGE: January 30, 2007
JOURNAL FREE ACCESSGlutamate and reactive oxygen species including nitric oxide (NO) and superoxide anion (O2·-) have been postulated to play pivotal roles in the pathogenesis of the neuronal cell loss that is associated with several neurological disease states including Parkinson's disease and amyotrophic lateral sclerosis. In mesencephalic cultures, nondopaminergic neurons but not dopaminergic neurons are susceptible to NO cytotoxicity, although both types of neurons are damaged by glutamate. Methylphenylpyridium ion (MPP+) selectively enhances glutamate and NO cytotoxicity against dopaminergic neurons of mesencephalic cultures. It is suggested that glutathione plays an important role in the expression of NO-mediated glutamate cytotoxicity in dopaminergic neurons. In cultured spinal neurons, glutamate coadministered with the glutamate transporter inhibitor selectively damages motor neurons. Motor neurons are injured by NO, whereas non-motor neurons are protected by NO through the guanylyl cyclase-cGMP cascade. It is suggested that selective motor neuronal death caused by chronic low-level exposure to glutamate is mediated by the formation of NO in nonmotor neurons. It is possible that neurotoxicity induced by NO and O2·- associated with neurodegenerative disorders is regulated by intracellular defense systems such as glutathione and cGMP.View full abstractDownload PDF (8036K) -
Toshio MATSUDA, Kazuhiro TAKUMA, Eibai LEE, Akemichi BABA1999 Volume 114 Issue 5 Pages 281-286
Published: 1999
Released on J-STAGE: January 30, 2007
JOURNAL FREE ACCESSIncubation of cultured astrocytes in Ca2+-containing medium after exposure to Ca2+-free medium causes Ca2+ influx followed by delayed cell death. Here, we summarize the mechanisms underlying the Ca2+-mediated injury of cultured astrocytes and the protective effects of drugs against Ca2+-reperfusion injury. Our results show that Ca2+-reperfusion injury of astrocytes appears to be mediated by apoptosis as evidenced by DNA fragmentation and nuclear condensation. Calpain, reactive oxygen species (ROS) production, calcineurin, caspase-3, and NF-κB activation are involved in Ca 2+-reperfusion injury. Several drugs including T-588 and idebenone protect astrocytes against Ca2+-reperfusion injury. The protective effect of idebenone is mediated by nerve growth factor production, whereas that of T-588 is mediated mainly by the mitogen-activated protein/extracellular signal-regulated kinase signal cascade.View full abstractDownload PDF (6492K) -
Hiroko HASHIZUME, Yasushi ABIKO1999 Volume 114 Issue 5 Pages 287-293
Published: 1999
Released on J-STAGE: January 30, 2007
JOURNAL FREE ACCESSLysophosphatidylcholine (LPC) is an amphiphilic metabolite produced from membrane-phospholipids by the activation of phospholipase A2 (PLA2), and it accumulates in the ischemic myocardium. It has been demonstrated that exogenous LPC produces an increase in intracellular Ca2+ concentration ([Ca2+]i), morphological change from rod- to round-shape, and increase in release of creatine kinase (CK). The possible mechanism of the Ca2+ overload induced by LPC is direct Ca 2+ entry via a nonselective cation channel (or pore) or secondary Ca2+ entry via Na+-Ca2+ exchanger after increase in intracellular Na+ concentration. Among anti-ischemic drugs including β-adrenoceptor antagonists and Ca2+ channel blockers, a drug with high lipophilicity attenuates the LPC-induced cellular damage, probably due to the preservation of membrane integrity. Because LPC, which accumulates during ischemia and reperfusion of the heart, and produces Ca2+ overload, it is possible that LPC potentiates the ischemic injury in the heart. Therefore, development of protective drugs against cell injury induced by LPC would represent a new approach to finding new drugs that protect the heart against ischemic injury.View full abstractDownload PDF (6977K) -
Toru TAKAHASHI, Tsutomu SUZUKI, Akira YAMASAKI, Takashi TSUKIJI, Masah ...1999 Volume 114 Issue 5 Pages 295-302
Published: 1999
Released on J-STAGE: January 30, 2007
JOURNAL FREE ACCESSSevere sepsis is known to result in multiple organ dysfunction syndrome (MODS), which is thought to be mediated by oxidative stress, as a result of excessive systemic inflammation. Heme Oxygenase-1 (HO-1), the rate limiting enzyme in heme catabolism, is also known as HSP32. HO-1 is induced not only by its substrate heme but also by oxidative stress. We investigated gene expression of HO-1 and physiological significance of HO-1 induction in a rat model of septic MODS induced by intraperitoneal injection of bacterial lipopolysaccharide (LPS). Following administration of LPS, HO-1 mRNA was significantly induced in the liver, lung and kidney in an organ-specific manner. Hepatic HO-1 induction appears to be mediated by an increase in hepatic free heme concentration. Inhibition of HO-1 activity by tin mesoporphyrin significantly exacerbated lung injury. These results suggest that HO-1 induction may play an important role in conferring protection on cells from oxidative damage not only by catalyzing heme, a pro-oxidant, but also by producing bilirubin, an anti-oxidant. Furthermore, HO-1 mRNA is induced markedly in the buffy coat of the blood at 3 h after LPS administration, coinciding with the increase in serum IL-6 level, suggesting that HO-1 may be one of the key markers of septic MODS.View full abstractDownload PDF (9127K) -
Takashi TOMIUGA, Yasuhiro AKIYAMA, Masatoshi KOBAYASHI, Kuniko HARA, H ...1999 Volume 114 Issue 5 Pages 303-313
Published: 1999
Released on J-STAGE: January 30, 2007
JOURNAL FREE ACCESSTwo experiments were carried out in 4-week-old rats. First, the effect of dietary calcium (Ca) content (0.05, 0.1, 0.2, 0.5 and 1.16%) on bone loss was assessed for 3 weeks. Dry weight of the femur showed a Ca-content-dependent decrease. Significant decrease in body weight and plasma Ca level was observed in the 0.05 and 0.1% Ca diet groups, but not in other groups. Second, the curative effect of V.K2 on bone strength was examined. After being fed a 0.2%-Ca diet for 3 weeks, rats were fed 0.2% or 0.5%-Ca diets for the next 6 weeks with or without V.K2 treatment. At the beginning and after 3 and 6 weeks of treatment, femurs and lumbar vertebra (L3) were collected. In the 0.2%-Ca group, bone mineral density (BMD) and bone strength in the femur gradually increased, but were much lower than those in the intact group. In the 0.5%-Ca group, both parameters in the femur and L3 were rapidly increased. V.K2 treatment did not affect the BMD or bone strength in the femur at either point. However, the bone strength in L3 in the V.K2 group was higher than that in the 0.5%-Ca group at 3 weeks and in the 0.2%-Ca group at 6 weeks than that in the respective control group. These findings suggest that V.K2 has curative effect on bone strength in the vertebra.View full abstractDownload PDF (10309K)
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