Protective mechanism of glutamine on the expression of proliferating cell nuclear antigen after cisplatin-induced intestinal mucosal injury
Protective mechanism of glutamine on the expression of proliferating cell nuclear antigen after cisplatin-induced intestinal mucosal injury
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DOI：
10.1007/s00383-010-2798-8
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发表时间：
2011-02-01
影响因子：
1.8
通讯作者：
Fukuzawa, Masahiro
中科院分区：
文献类型：
--
作者：
Tazuke, Yuko;Maeda, Kosaku;Fukuzawa, Masahiro
谷氨酰胺可预防化疗引起的肠粘膜损伤。然而，其机制尚未阐明。增殖细胞核抗原（PCNA）在细胞周期的DNA合成阶段在细胞核中表达，并且PCNA还参与称为复制后修复的DNA损伤耐受途径。我们假设补充谷氨酰胺可能会刺激化疗引起的肠上皮细胞周期中断。观察顺铂致肠黏膜损伤后补充谷氨酰胺对PCNA表达的影响。将雄性Wister大鼠分为3组；对照组（对照组 n = 5），接受标准大鼠饮食； Cis 组（顺铂 6 mg/kg 腹腔注射，n = 5），以及 Cis + Gln 组 [顺铂 + 丙氨酸谷氨酰胺（0.5 g/天 x 3 天口服，n = 5）]。化疗第1、3和7天后，研究了小肠（空肠和回肠）中PCNA和谷氨酰胺转运蛋白（ASCT2）的表达。化疗后小肠隐窝（空肠和回肠）中PCNA的表达下降，而谷氨酰胺给药后表达强烈增加，即使是在化疗后。第1天，给予谷氨酰胺（Cis+Gln组）后，隐窝细胞中谷氨酰胺转运蛋白（ASCT2）的mRNA表达和PCNA表达均显着增加。 ACST2 表达的增加出现早于 Cis 组。 Cis+Gln组第3天PCNA表达正常化，第3天表达与对照组相同。补充谷氨酰胺可迅速改善顺铂诱导的肠粘膜损伤后PCNA的表达。谷氨酰胺的作用可能是由于抗氧化作用，但氨基酸也可能减轻最初的粘膜损伤并改善肠细胞更新。
Glutamine prevents the intestinal mucosal injury induced by chemotherapy. However, the mechanism has not yet been elucidated. Proliferating cell nuclear antigen (PCNA) is expressed in the nuclei of cells during the DNA synthesis phase of the cell cycle, and PCNA is also involved in the DNA damage tolerance pathway known as post-replication repair. We hypothesized that glutamine supplementation might stimulate the intestinal epithelial cell cycle interruption induced by chemotherapy. The effect of supplemental glutamine after cisplatin-induced intestinal mucosal injury on the expression of PCNA was investigated.The male Wister rats were divided into three groups; a control group (control n = 5), which received standard rat diet; the Cis group (cisplatin 6 mg/kg i.p., n = 5), and the Cis + Gln group [cisplatin + Ala-Glutamine (0.5 g/day x 3 days p.o., n = 5)]. After 1, 3, and 7 days of chemotherapy, PCNA, and glutamine transporter (ASCT2) expression in the small intestine (jejunum and ileum) was investigated.The expression of PCNA in the crypt of the small intestine (jejunum and ileum) decreased after chemotherapy, while the expression strongly increased by glutamine administration, even if it was after chemotherapy. On day 1, both the mRNA expression of the glutamine transporter (ASCT2) and PCNA expression in crypt cells were significantly increased by administration of glutamine (Cis + Gln group). The increased expression of ACST2 appeared earlier than in the Cis group. In the Cis + Gln group, the PCNA expression was normalized on day 3, and the expression was same as that in the control group on day 3.Glutamine supplementation rapidly improved the expression of PCNA after cisplatin-induced intestinal mucosal injury. The effects of glutamine may be due to an anti-oxidant effect, but the amino acid might also attenuate the initial mucosal injury and improve intestinal cell turnover.