Production of superoxide anion and its physiological roles in gastric mucosal cells

胃粘膜细胞超氧阴离子的产生及其生理作用

• 批准号: 11670508
• 负责人: TESHIMA Shigetada
• 金额: $ 2.37万
• 依托单位: The University of Tokushima
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1999
• 资助国家: 日本
• 起止时间: 1999 至 2000
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-11670508/
• 关键词: gastric pit cells; superoxide anion; reactive oxygen intermediates; helicobacter pylori; Mox1 oxidase; apoptosis

We demonstrated that primary cultures of guinea pig gastric pit cells expressed all of the phagocyte NADPH oxidase components (p22-, p67-, p47-, and p40-phoxes) and could spontaneously release superoxide anion. We also identified that pit cells express a nonphagocyte-specific gp91-phox homolog (Mox1), but not gp91-phox. Lipopolysaccharide from Helico bacter pylori markedly enhanced the Mox1 oxidase activity. Inclusion of catalase significantly inhibited pit cell growth. Scavenging superoxide anion and related oxidants by superoxide dismutase plus catalase or N-acetyl cysteine and inhibiting Mox1 oxidase by diphenylene iodonium activated caspase 3-like proteases and markedly enhanced chromatin condensation and DNA fragmentation. This accelerated apoptosis was completely blocked by a caspase inhibitor, z-Val-Ala-Asp-CH_2F.Mox1-derived reactive oxygen intermediates constitutively activated nuclear factor kB (NF-kB), and inhibition of this activity by NF-kB decoy oligodeoxynucleotide accelerated their spontaneous apoptosis. These results suggest that superoxide anion produced by the pit cell Mox1 oxidase may play a crucial role in the regulation of their spontaneous apoptosis as well as cell proliferation.

我们证明了豚鼠胃坑细胞的原代培养物表达所有吞噬细胞NADPH氧化酶成分（P22-，P67-，P47-和P40-磷酸），并可以自发释放上氧化物阴离子。我们还确定了PIT细胞表达非噬细胞特异性GP91-Phox同源物（MOX1），但不表达GP91-Phox。幽门螺杆菌的脂多糖显着增强了MOX1氧化酶活性。纳入过氧化氢酶会显着抑制坑细胞的生长。通过超氧化物歧化酶，过氧化氢酶或N-乙酰基半胱氨酸清除超氧化物阴离子和相关的氧化剂，并通过二苯基碘二氧烷激活的caspase 3类蛋白酶抑制MOX1氧化酶，并明显增强了染色素凝结和DNA碎片。 This accelerated apoptosis was completely blocked by a caspase inhibitor, z-Val-Ala-Asp-CH_2F.Mox1-derived reactive oxygen intermediates constitutively activated nuclear factor kB (NF-kB), and inhibition of this activity by NF-kB decoy oligodeoxynucleotide accelerated their spontaneous apoptosis.这些结果表明，坑细胞MOX1氧化酶产生的超氧化阴离子可能在调节其自发凋亡以及细胞增殖中起着至关重要的作用。

项目成果

手嶋茂忠: "フリーラジカルの臨床"近藤元治,吉川敏一. 81 (2000)

Shigetada Teshima：“自由基的临床研究”Motoharu Kondo，Toshikazu Yoshikawa 81（2000）。

Kazuhito Rokutan: "Geranylgeranylacetone stimulates mucin synthesis in cultured guinea pig gastric pit cells through inducing a neuronal nitric oxide synthase.1"J.Gastroenterol.. 35(9). 673-681 (2000)

Kazuhito Rokutan：“香叶基香叶基丙酮通过诱导神经元一氧化氮合酶刺激培养的豚鼠胃凹细胞中的粘蛋白合成。1”J.Gastroenterol.. 35(9)。

Kazuhito Rokutan: "Phenylarsine oxide inhibits heat shock protein 70 induction in cultured guinea pig mucosal cells"Am.J.Physiol.. 279(5). C1506-C1515 (2000)

Kazuhito Rokutan：“氧化苯胂抑制培养豚鼠粘膜细胞中热休克蛋白 70 的诱导”Am.J.Physiol.. 279(5)。

Teshima, S., Kutsumi, H., Kawahara, T., Kishi, K., and Rokutan, K.: "Regulation of growth and apoptosis of cultured guinea pig gastric mucosal cells by mitogenic oxidase 1."Am.J.Physiol.. 279(6). G1169-G1176 (2000)

Teshima, S.、Kutsumi, H.、Kawahara, T.、Kishi, K. 和 Rokutan, K.：“有丝分裂氧化酶 1 对培养的豚鼠胃粘膜细胞的生长和凋亡的调节。”Am.J.Physiol

Teshima, S., Kawahara, T., and Rokutan, K.: "In : Free Radicals in Clinical Medicine"Kondo, M.and Yoshikawa, T.Edited. (2000)

Teshima, S.、Kawahara, T. 和 Rokutan, K.：“临床医学中的自由基”Kondo, M. 和 Yoshikawa, T. 编辑。