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.

我们证明豚鼠胃小凹细胞的原代培养物表达所有吞噬细胞NADPH氧化酶组分（p22-，p67-，p47-和p40-phoxes），并能自发释放超氧阴离子。我们还发现，小凹细胞表达非吞噬细胞特异性的gp 91-phox同源物（Mox 1），但不是gp 91-phox。幽门螺杆菌脂多糖显著增强Mox 1氧化酶活性。过氧化氢酶抑制纹孔细胞的生长。清除超氧阴离子和相关氧化剂的超氧化物歧化酶加过氧化氢酶或N-乙酰半胱氨酸和抑制Mox 1氧化酶的二苯碘鎓激活caspase 3样蛋白酶，显着增强染色质凝聚和DNA片段化。Caspase抑制剂z-Val-Ala-Asp-CH_2F.Mox1衍生的活性氧中间体组成性激活核因子kB（NF-kB）可完全阻断这种加速的凋亡，而NF-kB诱骗寡核苷酸抑制这种活性可加速其自发凋亡。这些结果表明，超氧阴离子产生的坑细胞Mox 1氧化酶可能在其自发凋亡以及细胞增殖的调节中发挥了至关重要的作用。

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

Rokutan, K., Miyoshi, M., Teshima, S., Kawai, T., Kawahara, T., and Kishi, K.: "Phenylarsine oxide inhibits heat shock protein 70 induction in cultured guinea pig mucosal cells"Am.J.Physiol.. 279(5). C1506-C1515 (2000)

Rokutan, K.、Miyoshi, M.、Teshima, S.、Kawai, T.、Kawahara, T. 和 Kishi, K.：“苯胂氧化抑制培养豚鼠粘膜细胞中热休克蛋白 70 的诱导”Am.J