Adaptive responses induced by 24S-hydroxycholesterol through liver X receptor pathway reduce 7-ketocholesterol-caused neuronal cell death.
Adaptive responses induced by 24S-hydroxycholesterol through liver X receptor pathway reduce 7-ketocholesterol-caused neuronal cell death.
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DOI：
10.1016/j.redox.2013.11.007
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发表时间：
2013
期刊：
影响因子：
11.4
通讯作者：
Noguchi N
中科院分区：
文献类型：
--
作者：
Okabe A;Urano Y;Itoh S;Suda N;Kotani R;Nishimura Y;Saito Y;Noguchi N
已知脂质过氧化产物通过上调抗氧化化合物和酶诱导细胞适应性反应并增强对随后氧化应激的耐受性。24 S-羟基胆固醇（24 SOHC）是脑内内源性产生的氧化固醇，在维持脑胆固醇稳态中起重要作用。在这项研究中，我们评估了脑特异性氧固醇24 SOHC诱导的适应性反应在人神经母细胞瘤SH-SY 5 Y细胞。用亚致死浓度的24 SOHC处理的细胞显示在未分化和视黄酸分化的SH-SY 5 Y细胞中由7-酮基胆固醇（7 KC）随后处理诱导的细胞死亡显著减少。这些适应性反应也由其他氧固醇如25-羟基胆固醇和27-羟基胆固醇诱导，它们已知是肝X受体（LXR）的配体。共治疗24 SOHC与9-顺式视黄酸，类维生素A X受体配体，增强了适应性反应。通过siRNA敲低LXRβ几乎完全减弱了24 SOHC诱导的适应性反应。24 SOHC处理诱导LXR靶基因的表达，如ATP结合盒转运蛋白A1（ABCA 1）和G1（ABCG 1）。24 SOHC诱导的适应性反应被针对ABCG 1的siRNA显著减弱，但不被针对ABCA 1的siRNA减弱。总之，这些结果强烈表明，亚致死浓度的24 SOHC通过LXR信号传导途径的转录激活诱导适应性反应，从而保护神经元细胞免受随后的7 KC诱导的细胞毒性。24 SOHC在神经元细胞中诱导针对7 KC诱导的细胞死亡的适应性反应。24 SOHC与RXR配体9 cRA的共处理增强了适应性反应。LXRβ的敲低抑制24 SOHC诱导的适应性反应。ABCG 1参与24 SOHC介导的LXR介导的适应性反应。
Lipid peroxidation products have been known to induce cellular adaptive responses and enhance tolerance against subsequent oxidative stress through up-regulation of antioxidant compounds and enzymes. 24S-hydroxycholesterol (24SOHC) which is endogenously produced oxysterol in the brain plays an important role in maintaining brain cholesterol homeostasis. In this study, we evaluated adaptive responses induced by brain-specific oxysterol 24SOHC in human neuroblastoma SH-SY5Y cells. Cells treated with 24SOHC at sub-lethal concentrations showed significant reduction in cell death induced by subsequent treatment with 7-ketocholesterol (7KC) in both undifferentiated and retinoic acid-differentiated SH-SY5Y cells. These adaptive responses were also induced by other oxysterols such as 25-hydroxycholesterol and 27-hydroxycholesterol which are known to be ligands of liver X receptor (LXR). Co-treatment of 24SOHC with 9-cis retinoic acid, a retinoid X receptor ligand, enhanced the adaptive responses. Knockdown of LXRβ by siRNA diminished the adaptive responses induced by 24SOHC almost completely. The treatment with 24SOHC induced the expression of LXR target genes, such as ATP-binding cassette transporter A1 (ABCA1) and G1 (ABCG1). The 24SOHC-induced adaptive responses were significantly attenuated by siRNA for ABCG1 but not by siRNA for ABCA1. Taken together, these results strongly suggest that 24SOHC at sub-lethal concentrations induces adaptive responses via transcriptional activation of LXR signaling pathway, thereby protecting neuronal cells from subsequent 7KC-induced cytotoxicity. 24SOHC induces adaptive responses against 7KC-induced cell death in neuronal cells. Co-treatment of 24SOHC with 9cRA, an RXR ligand enhances adaptive responses. Knockdown of LXRβ suppresses 24SOHC-induced adaptive responses. ABCG1 is involved in LXR-mediated adaptive responses by 24SOHC.
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影响因子：
16.6
作者：
Russell DW;Halford RW;Ramirez DM;Shah R;Kotti T
通讯作者：
Kotti T
DOI：
10.1073/pnas.96.13.7238
发表时间：
1999-06-22
影响因子：
11.1
作者：
Lund, EG;Guileyardo, JM;Russell, DW
通讯作者：
Russell, DW
影响因子：
4.8
作者：
Bjorkhem, I;Lutjohann, D;Wennmalm, A
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Wennmalm, A
影响因子：
2.9
作者：
Kölsch, H;Lütjohann, D;Rao, ML
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Rao, ML
影响因子：
4.8
作者：
Chen, Zhi-Hua;Yoshida, Yasukazu;Niki, Etsuo
通讯作者：
Niki, Etsuo