Nutrition and the regulation of higher animals in hypoxia

高等动物缺氧的营养与调节

• 批准号: 09660143
• 负责人: NAKANO Yoshihisa
• 金额: $ 1.86万
• 依托单位: Osaka Prefecture University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1997
• 资助国家: 日本
• 起止时间: 1997 至 1999
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-09660143/
• 关键词: Hypoxia; Gastrin; Epo (erythropoietin); GAPDH (glyceraldehydes-3-phosphate dehydrogenase); MBEC4; iNOS; Vitamin BィイD212ィエD2; 低酸素; ビタミンB_<12>欠乏ラット; スレオニンデヒドラターゼ活性; 赤血球分化; 巨赤芽球細胞; VEGF; エリスロポエチン受容体; NO; NO合成酵素; GAPOH; 胃酸分泌制御; アドレナリン; ノルアド

Hyoixia (10.5 or 7.6%OィイD22ィエD2) delayed gastric emptying and suppressed gastric acid secretion in conscious rats. In addition, although the concentration of plasma gastrin, the principal stimulant of gastric acid secretion, increased under hypoxic conditions, the oral administration of HCL abolished the hypoxia-stimulated gastrin release, indicating that the inhibitory effect of hypoxia on gastric acid secretion stimulates gastrin release through positive feedback regulation.The 10.5%OィイD22ィエD2 hypoxia-suppressed gastric acid secretion was restored to nearly the level in normoxia by the adrenal medullectomy. With 7.6%OィイD22ィエD2hypoxia, the operation also caused an increase in the level of gastric acid output, although the extent was lower than that with 10.5%OィイD22ィエD2hypoxia. Similar results were obtained when reserpine, which causes an adrenaergic discharge, was administered. Furthermore, an α2-adrenoceptor blocking agent, yohimbine, almost completely removed the inhibitory effect o … More f 10.5% and 7.6% OィイD22ィエD2hypoxia on gastric and secretion. Epinephrine release is stimulated by 10.5%OィイD22ィエD2hypoxia, and not only epinephrine but also norepinephrine releases are enhanced by 7.6%OィイD22ィエD2hypoxia. It is suggested that the hypoxia-stimulated adrenergic response acts on the α2-adrenoceptor on the vagus cholinergic endings in the gastric wall, and that the deareased acetylcholine release thereby inhibits gastric acid secretion.Epo functioned as a competence factor for RBECs and maximally stimulated DNA synthesis of RBECs at the concentration of 1 U/ml (the serum concentrations of Epo in most animals are in the range 10 - 30 mU/ml under normal physiological conditions and increase more than 100-fold in hypoxemia resulting from anemia and hypoxic exposure). Furthermore, both RBECs and MBECs expressed two form Epo-R mNRA, the authentic form (aEpo-R) and the intron 5-inserted form (15 Epo-R). RBECs had a single class of low affinity (860 pM) binding site for Epo. These results suggest that rat and murine 15Epo-Rs modulate the functions of Epo by competing the binding of Epo with the authentic receptor as a membrane-bound form and a soluble form, respectively, and that Epo acts on endothelial cells as a competent factor when excess Epo is induced by hypoxia.Hypoxia (2%OィイD22ィエD2) stimulated the expression of GAPDH mRNA in all cell typed tested (MBEC4, Hep G2 CHO cells, Ba/F3 cells and rat sooth muscle cells). Some transition metals (CoィイD12+ィエD1, NiィイD12+ィエD1, ZnィイD12+ィエD1 and MnィイD12+ィエD1) and DFX also upregulated the transcription of GAPDH gene in MBEC4, suggesting that GAPDH is regulated through a mechanism, in which heme protein participates. iNOS was also induced in hypoxia and then cGMP was extremely formed, suggesting that cGMP acts as a intracellular information transmitter.Vitamin BィイD212ィエD2 is known as a developmental factor of blood cell. We have studied how the vitamin BィイD212ィエD2 affects on the development of blood cell in hypoxia. Less

低氧（10.5%或7.6%O_（22）O_（22）O_（22）D_（22））可延迟清醒大鼠胃排空，抑制胃酸分泌。此外，虽然血浆胃泌素（胃酸分泌的主要刺激物）的浓度在缺氧条件下增加，但口服HCL可消除缺氧刺激的胃泌素释放，提示缺氧对胃酸分泌的抑制作用通过正反馈调节促进胃泌素的释放，10.5%O_（22）O_（22）通过肾上腺髓质切除术，抑制的胃酸分泌恢复到接近常氧水平。在缺氧7.6%O_（22）O_（2利血平引起肾上腺素能放电时，也得到类似的结果。此外，α2-肾上腺素受体阻断剂育亨宾几乎完全消除了抑制作用。 ...更多信息 f 10.5%和7.6%的O-3D 22-D2缺氧对胃和分泌物的影响。10.5%O·OH·D22·OH·D2缺氧刺激肾上腺素释放，7.6%O·OH·D22·OH·D2缺氧不仅促进肾上腺素释放，而且促进去甲肾上腺素释放。提示缺氧刺激的肾上腺素能反应作用于胃壁迷走胆碱能末梢上的α2肾上腺素能受体，Epo对红细胞具有感受态作用，当浓度为1U/ml时，对红细胞DNA合成的刺激作用最大（在正常生理条件下，大多数动物中Epo的血清浓度在10 - 30 mU/ml的范围内，并且在由贫血和低氧暴露引起的低氧血症中增加超过100倍）。此外，RBEC和MBEC均表达两种形式的Epo-R mNRA，即真实形式（aEpo-R）和内含子5插入形式（15 Epo-R）。红细胞内皮细胞有一个单一的类低亲和力（860 pM）结合部位的Epo。这些结果表明，大鼠和小鼠15 Epo-Rs通过分别以膜结合形式和可溶形式竞争Epo与真实受体的结合来调节Epo的功能，并且当缺氧诱导过量Epo时，Epo作为感受态因子作用于内皮细胞。（2%O-22-D2）刺激所有测试类型的细胞（MBEC 4、Hep G2 CHO细胞、Ba/F3细胞和大鼠平滑肌细胞）中GAPDH mRNA的表达。某些过渡金属（Co ~（2+）D_12 + Zn ~（2+）D_1、Ni ~（2+）D_12 + Zn ~（2+）D_1和Mn ~（2+）D_12 + Zn ~（2+）D_1）和DFX也能上调MBEC 4中GAPDH基因的转录，提示GAPDH的调控机制中有血红素蛋白参与。iNOS在缺氧时也被诱导，cGMP大量生成，提示cGMP是细胞内信息传递者。维生素B受体D2 12受体D2是血细胞发育因子。本文研究了维生素B族维生素D_（212）、维生素D_（212）对缺氧条件下血细胞发育的影响。少

项目成果

中野長久: "食を楽しみ健やかに生きるために" 糸川嘉則, 458 (1997)

Nagahisa Nakano：“享受食物，过健康的生活” Yoshinori Itokawa，458 (1997)

Nalano, Y.: "α2-Adrenoceptor-Mediated Antisecretory Effect of Hypoxia in Conscious Rats"Biosci. Biotech. Biochem.. 62(3). 546-549 (1998)

Nalano，Y.：“意识大鼠中缺氧的α2-肾上腺素受体介导的抗分泌作用”Biosci.Biochem.. 546-549 (1998)。

Yoshihisa Nakano: "α2-Adrenoceptor-Mediated Autisecretory Effect of Hypoxia in Conscious Rats" Biosci.Biotech.Biochem.62. 546-549 (1998)

Yoshihisa Nakano：“α2-肾上腺素受体介导的清醒大鼠缺氧的自分泌效应”Biosci.Biotech.Biochem.62 546-549（1998）。

Yosihisa Nakano: "The intron 5-inserted form of rat erythropoietin receptor is expressed as a membrane-bound form" Biochimica et Biophysica Acta. 1403. 169-178 (1998)

Yosihisa Nakano：“大鼠促红细胞生成素受体的内含子 5 插入形式以膜结合形式表达”Biochimica et Biophysicala Acta。

Nakano Yoshihisa: "The intron 5-inserted form of rat erythropoietin receptor is expressed as a membrane-bound form"Biochim.Biophys.Acta. 1403. 169-178 (1998)

Nakano Yoshihisa：“大鼠促红细胞生成素受体的内含子 5 插入形式以膜结合形式表达”Biochim.Biophys.Acta。