活化过氧化物酶体增殖物活化受体γ抑制血清剥夺诱导的lc - pk1细胞凋亡。

Kazutaka Haraguchi, Hiroki Shimura, Toshimasa Onaya
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引用次数: 7

摘要

过氧化物酶体增殖体激活受体- γ (PPARgamma)属于核受体超家族,在脂质和葡萄糖代谢中起重要作用。然而,PPARgamma在脂肪外组织中的表达和PPARgamma激活剂对细胞凋亡的刺激已有报道。我们利用克隆肾细胞系(LLC-PK1)研究了PPARgamma的功能。RT-PCR结果显示PPARgamma在LLC-PK1细胞中表达。细胞对曲格列酮(PPARgamma的一种配体)的反应是积累脂肪滴和增加游离脂肪酸的β -氧化。在生理浓度下,PPARgamma的配体包括曲格列酮、BRL49653和15-脱氧- δ -12,14-前列腺素J(2)抑制血清剥夺诱导的细胞凋亡。另一方面,ppar激活剂对细胞凋亡没有抑制作用。lc - pk1细胞的凋亡是通过细胞活力测定、荧光显微镜和电子显微镜下细胞核的冷凝以及琼脂糖凝胶上核小体阶梯的DNA片段来确定的。曲格列酮还能抑制血清剥夺诱导的Caspase 3的激活。然而,曲格列酮不能抑制ATP剥夺引起的细胞凋亡。曲格列酮的抗凋亡作用被磷脂酰肌醇-3激酶(PI3K)抑制剂wortmannin部分阻断,但不被其他激酶抑制剂如PD98059和AG490阻断。这些结果表明,PPARgamma在lc - pk1细胞中具有功能性表达,其激活至少部分通过PI3K途径抑制血清剥夺诱导的细胞凋亡。
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Activation of peroxisome proliferator-activated receptor-gamma inhibits apoptosis induced by serum deprivation in LLC-PK1 cells.

Peroxisome proliferator-activated receptor-gamma (PPARgamma) belongs to a superfamily of nuclear receptors, which plays important roles in lipid and glucose metabolism. However, expression of PPARgamma in extra-adipose tissues and stimulation of apoptosis by PPARgamma activators has been previously reported. We investigated the functions of PPARgamma using a clonal kidney cell line (LLC-PK1). RT-PCR revealed the expression of PPARgamma in LLC-PK1 cells. The cells accumulated fat droplets and increased beta-oxidation of free fatty acids in response to troglitazone, a ligand for PPARgamma. At physiological concentrations, ligands for PPARgamma including troglitazone, BRL49653, and 15-deoxy-delta-12,14-prostaglandin J(2) inhibited serum-deprivation-induced apoptosis of the cells. On the other hand, PPARalpha activators did not inhibit the apoptosis. Apoptosis of LLC-PK1 cells was determined by a cell viability assay, condensation of the nucleus on fluorescent and electron microscopy, and DNA fragmentation as indicated by the appearance of nucleosomal ladders on an agarose gel. Troglitazone also suppressed serum-deprivation-induced activation of Caspase 3. However, troglitazone did not suppress apoptosis induced by ATP deprivation. Anti-apoptotic effects of troglitazone were partially blocked by a phosphatidylinositol-3-kinase (PI3K) inhibitor, wortmannin, but not by other kinase inhibitors such as PD98059 and AG490. These results suggest that PPARgamma is functionally expressed in LLC-PK1 cells, and its activation inhibits apoptosis induced by serum deprivation, at least in part, through the PI3K pathway.

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