Adaptive responses induced by 24S-hydroxycholesterol through liver X receptor pathway reduce 7-ketocholesterol-caused neuronal cell death
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 impo...
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doaj-90821d4ec99c4abc8c00a81b54342bb82020-11-24T21:52:59ZengElsevierRedox Biology2213-23172014-01-012C283510.1016/j.redox.2013.11.007Adaptive responses induced by 24S-hydroxycholesterol through liver X receptor pathway reduce 7-ketocholesterol-caused neuronal cell deathAkishi OkabeYasuomi UranoSayoko ItohNaoto SudaRina KotaniYuki NishimuraYoshiro SaitoNoriko Noguchi 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. http://www.sciencedirect.com/science/article/pii/S2213231713000876Cell deathAdaptive responsesLiver X receptor24S-hydroxycholesterol7-ketocholesterolATP-binding cassette transporter G1 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Akishi Okabe Yasuomi Urano Sayoko Itoh Naoto Suda Rina Kotani Yuki Nishimura Yoshiro Saito Noriko Noguchi |
spellingShingle |
Akishi Okabe Yasuomi Urano Sayoko Itoh Naoto Suda Rina Kotani Yuki Nishimura Yoshiro Saito Noriko Noguchi Adaptive responses induced by 24S-hydroxycholesterol through liver X receptor pathway reduce 7-ketocholesterol-caused neuronal cell death Redox Biology Cell death Adaptive responses Liver X receptor 24S-hydroxycholesterol 7-ketocholesterol ATP-binding cassette transporter G1 |
author_facet |
Akishi Okabe Yasuomi Urano Sayoko Itoh Naoto Suda Rina Kotani Yuki Nishimura Yoshiro Saito Noriko Noguchi |
author_sort |
Akishi Okabe |
title |
Adaptive responses induced by 24S-hydroxycholesterol through liver X receptor pathway reduce 7-ketocholesterol-caused neuronal cell death |
title_short |
Adaptive responses induced by 24S-hydroxycholesterol through liver X receptor pathway reduce 7-ketocholesterol-caused neuronal cell death |
title_full |
Adaptive responses induced by 24S-hydroxycholesterol through liver X receptor pathway reduce 7-ketocholesterol-caused neuronal cell death |
title_fullStr |
Adaptive responses induced by 24S-hydroxycholesterol through liver X receptor pathway reduce 7-ketocholesterol-caused neuronal cell death |
title_full_unstemmed |
Adaptive responses induced by 24S-hydroxycholesterol through liver X receptor pathway reduce 7-ketocholesterol-caused neuronal cell death |
title_sort |
adaptive responses induced by 24s-hydroxycholesterol through liver x receptor pathway reduce 7-ketocholesterol-caused neuronal cell death |
publisher |
Elsevier |
series |
Redox Biology |
issn |
2213-2317 |
publishDate |
2014-01-01 |
description |
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.
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topic |
Cell death Adaptive responses Liver X receptor 24S-hydroxycholesterol 7-ketocholesterol ATP-binding cassette transporter G1 |
url |
http://www.sciencedirect.com/science/article/pii/S2213231713000876 |
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