Role of Putrescine in Vitamin D-Dependent Intestinal Cell Differentiation.

腐胺在维生素 D 依赖性肠细胞分化中的作用。

• 批准号: 01571028
• 负责人: SHINKI Toshimasa
• 金额: $ 1.34万
• 依托单位: Showa University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (C)
• 财政年份: 1989
• 资助国家: 日本
• 起止时间: 1989 至 1990
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-01571028/
• 关键词: 1alpha, 25-dihydroxyvitamin D_3; Intestine; Ca transport; polyamine; putrescine; ODC; Ca-ATPase; villus; ポリアミン酸化酵素

1alpha, 25-Dihydroxyvitamin D_3 (1alpha, 25(OH)_2D_3), the most potent metabolite of vitamin D_3, is now considered to be a hormone witch mediates calcium transport in the target tissues such as intestine and bone. Intestinal mucosal cells have a relatively short life span. They originate in progenitor cells present in the crypt region of the villi and differentiate and migrate toward the villus tips, where they are extruded into the lumen within 4 days. Polyamines are ubiquitous polycationic compounds of low molecular weight. The compounds are involved in cell proleration and differentiation in many cells. Three major polyamines (putrescine, spermidine, and spermine) are synthesized sequentially from ornithine. Ornithine decarboxylase (ODC) catalyzes the formation of putrescine from ornithine, a ratelimiting step in polyamine biosynthesis. Recently several reserchers have suggested the possibility that there is a conversion of the higher polyamines (spermidine and spermine) back into … More putrescine. In the present study, the effects of putrescine depletion and its supplementation on the duodenal villus length and calcium absorption were examined in chicks. Administration of either alpha-difluoro-methylornithine, a specific inhibitor of ornithine decarboxylase, or N^1,N^4-bis (2, 3-butadieny1)-1, 4-butanediamine, a specific inhibitor of polyamine oxidase, to chicks significantly decreased the duodenal content of putrescine and calcium transport activity. The putrescine depletion also induced shortening of the duodenal villus length. The inhibition of calcium absorption and villus length in the putrescine depleted chicks was almost completely restored by administering putrescine to the bird. The 1alpha, 25(OH)_2D_3 treatment increased both calcium absorption and the ATP-dependent calcium uptake by the basolateral membrane, but had no effect on the calcium uptake by the brush border membrane in the chick intestine. The duodenal basolateral membrane showed two distinct Ca^<2+>-ATPase activities : a high and low-affinity type (apparent Km for Ca^<2+> : 0.24 and 1.28muM, respectively). Treatment with 1alpha, 25-(OH)_2D_3 increased the Vmax value of the high-affinity type Ca^<2+>-ATPase without any change in the Km value. Sodium dodecyl sulfate polyacrylamide gel electrophoretic analysis revealed the formation of a calcium-dependent phosphorylated intermediate with an apparent molecular mass of 105 kD in the basolateral membrane from the intestine. These results indicate that the initial enhancement of intestinal calcium absorption induced by 1 alpha, 25(OH)_2D_3 is due to an increase in the calcium efflux mediated by the calcium pump at the basolateral membrane. In conclusion, putrescine is somehow involved in the vitamin D action in maintaining the morphological and functional development of the intestinal villus mucosa. Less

1 α，25-二羟基维生素D_3（1 α，25（OH）_2D_3）是维生素D_3最强的代谢产物，目前被认为是一种调节肠、骨等靶组织钙转运的激素。肠粘膜细胞的寿命相对较短。它们起源于存在于绒毛的隐窝区域中的祖细胞，并分化并向绒毛尖端迁移，在那里它们在4天内被挤出到管腔中。聚胺是普遍存在的低分子量聚阳离子化合物。这些化合物参与许多细胞的细胞增殖和分化。三种主要的多胺（腐胺、亚精胺和精胺）由鸟氨酸依次合成。鸟氨酸脱羧酶（ODC）催化多胺生物合成中的限速步骤--由鸟氨酸生成腐胺。最近，一些研究者提出了高级多胺（亚精胺和精胺）转化回 ...更多信息 腐胺本试验研究了腐胺耗竭和补充腐胺对雏鸡十二指肠绒毛长度和钙吸收的影响。给雏鸡施用α-二氟甲基鸟氨酸（一种特异性的鸟氨酸脱羧酶抑制剂）或N^1，N^4-双（2，3-丁二烯基）-1，4-丁二胺（一种特异性的多胺氧化酶抑制剂）可显著降低十二指肠腐胺含量和钙转运活性。腐胺耗竭也引起十二指肠绒毛长度缩短。腐胺耗竭鸡对钙吸收和绒毛长度的抑制几乎完全恢复，通过给鸟施用腐胺。1 α，25（OH）_2D_3处理可增加鸡小肠基底膜钙吸收和ATP依赖性钙吸收，但对刷状缘膜钙吸收无影响。十二指肠基底外侧膜显示出两种不同的Ca^<2+>-ATP酶活性：高亲和力和低亲和力型（对Ca^<2+>的表观Km分别为0.24和1.28 μ M）。1 α，25-（OH）_2D_3处理后，高亲和型Ca^<2+>-ATPase的Vmax值增加，而Km值无明显变化。十二烷基硫酸钠聚丙烯酰胺凝胶电泳分析表明，形成的钙依赖性磷酸化中间体的表观分子量为105 kD的基底外侧膜从肠。上述结果表明，1 α，25（OH）_2D_3引起的小肠钙吸收的初始增强是由于基底膜钙泵介导的钙外排增加所致。总之，腐胺在某种程度上参与了维生素D维持肠绒毛粘膜形态和功能发育的作用。少

项目成果

SHINKI,T.: "Putrescine is the vitamin D action in chick intestine." Gastroenterology. 100. 113-122 (1991)

SHINKI,T.：“腐胺是维生素 D 在小鸡肠道中的作用。”

TAKITO,J.: "Calcium uptake by brush border and basolateral membrane vesicles in chick duodenum" American Journal of Physiology. 258. G16-G23 (1990)

TAKITO, J.：“鸡十二指肠刷状缘和基底外侧膜囊泡的钙吸收”美国生理学杂志。

SHINKI,T.: "Major pathway for putrescine synthesis induced by 1α,25ーdihydroxyvitamin D_3 in chick duodenum." Gastroenterology. 96. 1494-1501 (1989)

SHINKI, T.：“小鸡十二指肠中 1α,25-二羟基维生素 D_3 诱导腐胺合成的主要途径。” 96. 1494-1501 (1989)

SHINKI,T.: "Purification and characterization of spermidine N_1ーacetyltransferase from chick duodenum." European Journal of Biochemistry. 183. 285-290 (1989)

SHINKI, T.：“来自鸡十二指肠的亚精胺 N_1-乙酰转移酶的纯化和表征。”欧洲生物化学杂志 183. 285-290 (1989)

TANAKA,H.: "Spermidine-dependent proteins are involved in the fusion of mouse alveolar macrophages induce by 1α,25-dihydroxyvitamin D_3" Experimental Cell Research. 180. 72-83 (1989)

TANAKA, H.：“亚精胺依赖性蛋白参与 1α,25-二羟基维生素 D_3 诱导的小鼠肺泡巨噬细胞的融合”实验细胞研究 180. 72-83 (1989)。