5-Aminolevulinic Acid Attenuates Glucose-Regulated Protein 78 Expression and Hepatocyte Lipoapoptosis via Heme Oxygenase-1 Induction

Endoplasmic reticulum (ER) stress plays a pivotal role in the progression of steatohepatitis. 5-aminolevulinic acid (5-ALA), a precursor in the heme biosynthetic pathway, has recently been reported to induce heme oxygenase (HO)-1. HO-1 exerts important cytoprotective actions. In this study, we aimed...

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Autores principales:	Takaaki Hashimoto, Takaaki Sugihara, Tsutomu Kanda, Tomoaki Takata, Hajime Isomoto
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	endoplasmic reticulum stress heme oxygenase-1 glucose-regulated protein 78 steatohepatitis 5-aminolevulinic acid Biology (General) QH301-705.5 Chemistry QD1-999
Acceso en línea:	https://doaj.org/article/c3eb87c5c69749b9baa075e6366c62ae
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spelling	oai:doaj.org-article:c3eb87c5c69749b9baa075e6366c62ae2021-11-11T16:52:48Z5-Aminolevulinic Acid Attenuates Glucose-Regulated Protein 78 Expression and Hepatocyte Lipoapoptosis via Heme Oxygenase-1 Induction10.3390/ijms2221114051422-00671661-6596https://doaj.org/article/c3eb87c5c69749b9baa075e6366c62ae2021-10-01T00:00:00Zhttps://www.mdpi.com/1422-0067/22/21/11405https://doaj.org/toc/1661-6596https://doaj.org/toc/1422-0067Endoplasmic reticulum (ER) stress plays a pivotal role in the progression of steatohepatitis. 5-aminolevulinic acid (5-ALA), a precursor in the heme biosynthetic pathway, has recently been reported to induce heme oxygenase (HO)-1. HO-1 exerts important cytoprotective actions. In this study, we aimed to explore the therapeutic potential of 5-ALA on palmitate-induced ER stress and lipoapoptosis. Huh-7 cells were treated with palmitic acid (PA) (800 μM) to induce steatosis for eight hours. Steatosis was evaluated by Lipi-green staining. 5-ALA (200 μM) was added with PA. The gene expression levels of the nuclear factor erythroid 2–related factor 2 (<i>NRF2</i>), <i>HO-1</i>, Glucose-regulated protein 78 (<i>GRP78</i>), activating transcription factor 6 (<i>ATF6</i>), PKR-like endoplasmic reticulum kinase (<i>PERK</i>), inositol-requiring enzyme 1 (<i>IRE1</i>), C/EBP homologous protein (<i>CHOP</i>), and B-cell lymphoma 2 (<i>BCL-2</i>) were evaluated by RT-PCR. Caspase-3/7 activity was evaluated by fluorescein active Caspase-3/7 staining. Cell death was evaluated by Annexin V/SYTOX green staining. PA significantly induced steatosis and increased <i>GRP78</i> expression in Huh-7 cells. 5-ALA significantly induced <i>HO-1</i> and decreased <i>GRP78</i> expression. <i>ATF6</i> was subsequently decreased. However, <i>NRF2</i> and <i>CHOP</i> expression were not altered. Anti-apoptotic <i>BCL-2</i> expression significantly increased, and Caspase 3/7 activity and cell death also decreased. 5-ALA has a therapeutic potential on hepatic steatosis by suppressing ER stress and lipoapoptosis by attenuating <i>GRP78</i> via <i>HO-1</i> induction.Takaaki HashimotoTakaaki SugiharaTsutomu KandaTomoaki TakataHajime IsomotoMDPI AGarticleendoplasmic reticulum stressheme oxygenase-1glucose-regulated protein 78steatohepatitis5-aminolevulinic acidBiology (General)QH301-705.5ChemistryQD1-999ENInternational Journal of Molecular Sciences, Vol 22, Iss 11405, p 11405 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	endoplasmic reticulum stress heme oxygenase-1 glucose-regulated protein 78 steatohepatitis 5-aminolevulinic acid Biology (General) QH301-705.5 Chemistry QD1-999
spellingShingle	endoplasmic reticulum stress heme oxygenase-1 glucose-regulated protein 78 steatohepatitis 5-aminolevulinic acid Biology (General) QH301-705.5 Chemistry QD1-999 Takaaki Hashimoto Takaaki Sugihara Tsutomu Kanda Tomoaki Takata Hajime Isomoto 5-Aminolevulinic Acid Attenuates Glucose-Regulated Protein 78 Expression and Hepatocyte Lipoapoptosis via Heme Oxygenase-1 Induction
description	Endoplasmic reticulum (ER) stress plays a pivotal role in the progression of steatohepatitis. 5-aminolevulinic acid (5-ALA), a precursor in the heme biosynthetic pathway, has recently been reported to induce heme oxygenase (HO)-1. HO-1 exerts important cytoprotective actions. In this study, we aimed to explore the therapeutic potential of 5-ALA on palmitate-induced ER stress and lipoapoptosis. Huh-7 cells were treated with palmitic acid (PA) (800 μM) to induce steatosis for eight hours. Steatosis was evaluated by Lipi-green staining. 5-ALA (200 μM) was added with PA. The gene expression levels of the nuclear factor erythroid 2–related factor 2 (<i>NRF2</i>), <i>HO-1</i>, Glucose-regulated protein 78 (<i>GRP78</i>), activating transcription factor 6 (<i>ATF6</i>), PKR-like endoplasmic reticulum kinase (<i>PERK</i>), inositol-requiring enzyme 1 (<i>IRE1</i>), C/EBP homologous protein (<i>CHOP</i>), and B-cell lymphoma 2 (<i>BCL-2</i>) were evaluated by RT-PCR. Caspase-3/7 activity was evaluated by fluorescein active Caspase-3/7 staining. Cell death was evaluated by Annexin V/SYTOX green staining. PA significantly induced steatosis and increased <i>GRP78</i> expression in Huh-7 cells. 5-ALA significantly induced <i>HO-1</i> and decreased <i>GRP78</i> expression. <i>ATF6</i> was subsequently decreased. However, <i>NRF2</i> and <i>CHOP</i> expression were not altered. Anti-apoptotic <i>BCL-2</i> expression significantly increased, and Caspase 3/7 activity and cell death also decreased. 5-ALA has a therapeutic potential on hepatic steatosis by suppressing ER stress and lipoapoptosis by attenuating <i>GRP78</i> via <i>HO-1</i> induction.
format	article
author	Takaaki Hashimoto Takaaki Sugihara Tsutomu Kanda Tomoaki Takata Hajime Isomoto
author_facet	Takaaki Hashimoto Takaaki Sugihara Tsutomu Kanda Tomoaki Takata Hajime Isomoto
author_sort	Takaaki Hashimoto
title	5-Aminolevulinic Acid Attenuates Glucose-Regulated Protein 78 Expression and Hepatocyte Lipoapoptosis via Heme Oxygenase-1 Induction
title_short	5-Aminolevulinic Acid Attenuates Glucose-Regulated Protein 78 Expression and Hepatocyte Lipoapoptosis via Heme Oxygenase-1 Induction
title_full	5-Aminolevulinic Acid Attenuates Glucose-Regulated Protein 78 Expression and Hepatocyte Lipoapoptosis via Heme Oxygenase-1 Induction
title_fullStr	5-Aminolevulinic Acid Attenuates Glucose-Regulated Protein 78 Expression and Hepatocyte Lipoapoptosis via Heme Oxygenase-1 Induction
title_full_unstemmed	5-Aminolevulinic Acid Attenuates Glucose-Regulated Protein 78 Expression and Hepatocyte Lipoapoptosis via Heme Oxygenase-1 Induction
title_sort	5-aminolevulinic acid attenuates glucose-regulated protein 78 expression and hepatocyte lipoapoptosis via heme oxygenase-1 induction
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/c3eb87c5c69749b9baa075e6366c62ae
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5-Aminolevulinic Acid Attenuates Glucose-Regulated Protein 78 Expression and Hepatocyte Lipoapoptosis via Heme Oxygenase-1 Induction

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