Induction of apoptosis in human and rat glioma by agonists of the nuclear receptor PPARγ
Induction of apoptosis in human and rat glioma by agonists of the nuclear receptor PPARγ
复制标题
核受体 PPARγ 激动剂诱导人和大鼠神经胶质瘤细胞凋亡
DOI：
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发表时间：
2002
期刊：
影响因子：
--
通讯作者：
M. Heneka
中科院分区：
文献类型：
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作者：
T. Zander;J. Kraus;C. Grommes;U. Schlegel;D. Feinstein;T. Klockgether;G. Landreth;Jessica Koenigsknecht;M. Heneka
恶性星形细胞瘤是最常见的脑肿瘤之一，目前几乎没有治疗选择。最近人们认识到配体激活的核受体PPARγ可以调节不同恶性细胞的细胞增殖并诱导细胞凋亡。我们报道了三种结构不同的 PPARγ 激动剂诱导人（U87MG 和 A172）和大鼠（C6）神经胶质瘤细胞凋亡的作用。 PPARγ 激动剂环格列酮、LY171 833 和前列腺素-J2（但 PPARα 激动剂 WY14643）抑制增殖并诱导细胞死亡。 PPARγ 激动剂诱导的细胞死亡的特点是 DNA 断裂和核浓缩，并受到合成受体拮抗剂双酚 A 二缩水甘油醚 (BADGE) 的抑制。相反，原代鼠星形胶质细胞不受 PPARγ 激动剂治疗的影响。用 PPARγ 激动剂处理的神经胶质瘤细胞系中的细胞凋亡与 Bax 和 Bad 蛋白水平的瞬时上调相关。此外，通过特异性反义寡核苷酸抑制 Bax 表达可以保护神经胶质瘤细胞免受 PPARγ 介导的细胞凋亡，表明 Bax 在 PPARγ 诱导的细胞凋亡中发挥重要作用。然而，PPARγ 激动剂不仅诱导细胞凋亡，而且还引起再分化，如 PPARγ 激动剂响应的长过程的生长和再分化标记 N-钙粘蛋白的表达所表明的。总而言之，用 PPARγ 激动剂治疗神经胶质瘤细胞可能具有治疗神经胶质瘤的治疗潜力。
Malignant astrocytomas are among the most common brain tumours and few therapeutic options exist. It has recently been recognized that the ligand‐activated nuclear receptor PPARγ can regulate cellular proliferation and induce apoptosis in different malignant cells. We report the effect of three structurally different PPARγ agonists inducing apoptosis in human (U87MG and A172) and rat (C6) glioma cells. The PPARγ agonists ciglitazone, LY171 833 and prostaglandin‐J2, but not the PPARα agonist WY14643, inhibited proliferation and induced cell death. PPARγ agonist‐induced cell death was characterized by DNA fragmentation and nuclear condensation, as well as inhibited by the synthetic receptor‐antagonist bisphenol A diglycidyl ether (BADGE). In contrast, primary murine astrocytes were not affected by PPARγ agonist treatment. The apoptotic death in the glioma cell lines treated with PPARγ agonists was correlated with the transient up‐regulation of Bax and Bad protein levels. Furthermore, inhibition of Bax expression by specific antisense oligonucleotides protected glioma cells against PPARγ‐mediated apoptosis, indicating an essential role of Bax in PPARγ‐induced apoptosis. However, PPARγ agonists not only induced apoptosis but also caused redifferentiation as indicated by outgrowth of long processes and expression of the redifferentiation marker N‐cadherin in response to PPARγ agonists. Taken together, treatment of glioma cells with PPARγ agonists may hold therapeutic potential for the treatment of gliomas.
影响因子：
16
作者：
Mueller, E;Sarraf, P;Spiegelman, BM
通讯作者：
Spiegelman, BM
DOI：
10.1073/pnas.94.1.237
发表时间：
1997-01-07
影响因子：
11.1
作者：
Tontonoz, P;Singer, S;Spiegelman, BM
通讯作者：
Spiegelman, BM