Cargando…
Five-Aminolevulinic Acid (5-ALA) Induces Heme Oxygenase-1 and Ameliorates Palmitic Acid-Induced Endoplasmic Reticulum Stress in Renal Tubules
Steatosis, or ectopic lipid deposition, is the fundamental pathophysiology of non-alcoholic steatohepatitis and chronic kidney disease. Steatosis in the renal tubule causes endoplasmic reticulum (ER) stress, leading to kidney injury. Thus, ER stress could be a therapeutic target in steatonephropathy...
Autores principales: | , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2023
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10299457/ https://www.ncbi.nlm.nih.gov/pubmed/37373300 http://dx.doi.org/10.3390/ijms241210151 |
_version_ | 1785064368761733120 |
---|---|
author | Hamada, Shintaro Mae, Yukari Takata, Tomoaki Hanada, Hinako Kubo, Misaki Taniguchi, Sosuke Iyama, Takuji Sugihara, Takaaki Isomoto, Hajime |
author_facet | Hamada, Shintaro Mae, Yukari Takata, Tomoaki Hanada, Hinako Kubo, Misaki Taniguchi, Sosuke Iyama, Takuji Sugihara, Takaaki Isomoto, Hajime |
author_sort | Hamada, Shintaro |
collection | PubMed |
description | Steatosis, or ectopic lipid deposition, is the fundamental pathophysiology of non-alcoholic steatohepatitis and chronic kidney disease. Steatosis in the renal tubule causes endoplasmic reticulum (ER) stress, leading to kidney injury. Thus, ER stress could be a therapeutic target in steatonephropathy. Five-aminolevulinic acid (5-ALA) is a natural product that induces heme oxygenase (HO)-1, which acts as an antioxidant. This study aimed to investigate the therapeutic potential of 5-ALA in lipotoxicity-induced ER stress in human primary renal proximal tubule epithelial cells. Cells were stimulated with palmitic acid (PA) to induce ER stress. Cellular apoptotic signals and expression of genes involved in the ER stress cascade and heme biosynthesis pathway were analyzed. The expression of glucose-regulated protein 78 (GRP78), a master regulator of ER stress, increased significantly, followed by increased cellular apoptosis. Administration of 5-ALA induced a remarkable increase in HO-1 expression, thus ameliorating PA-induced GRP78 expression and apoptotic signals. BTB and CNC homology 1 (BACH1), a transcriptional repressor of HO-1, was significantly downregulated by 5-ALA treatment. HO-1 induction attenuates PA-induced renal tubular injury by suppressing ER stress. This study demonstrates the therapeutic potential of 5-ALA against lipotoxicity through redox pathway. |
format | Online Article Text |
id | pubmed-10299457 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-102994572023-06-28 Five-Aminolevulinic Acid (5-ALA) Induces Heme Oxygenase-1 and Ameliorates Palmitic Acid-Induced Endoplasmic Reticulum Stress in Renal Tubules Hamada, Shintaro Mae, Yukari Takata, Tomoaki Hanada, Hinako Kubo, Misaki Taniguchi, Sosuke Iyama, Takuji Sugihara, Takaaki Isomoto, Hajime Int J Mol Sci Article Steatosis, or ectopic lipid deposition, is the fundamental pathophysiology of non-alcoholic steatohepatitis and chronic kidney disease. Steatosis in the renal tubule causes endoplasmic reticulum (ER) stress, leading to kidney injury. Thus, ER stress could be a therapeutic target in steatonephropathy. Five-aminolevulinic acid (5-ALA) is a natural product that induces heme oxygenase (HO)-1, which acts as an antioxidant. This study aimed to investigate the therapeutic potential of 5-ALA in lipotoxicity-induced ER stress in human primary renal proximal tubule epithelial cells. Cells were stimulated with palmitic acid (PA) to induce ER stress. Cellular apoptotic signals and expression of genes involved in the ER stress cascade and heme biosynthesis pathway were analyzed. The expression of glucose-regulated protein 78 (GRP78), a master regulator of ER stress, increased significantly, followed by increased cellular apoptosis. Administration of 5-ALA induced a remarkable increase in HO-1 expression, thus ameliorating PA-induced GRP78 expression and apoptotic signals. BTB and CNC homology 1 (BACH1), a transcriptional repressor of HO-1, was significantly downregulated by 5-ALA treatment. HO-1 induction attenuates PA-induced renal tubular injury by suppressing ER stress. This study demonstrates the therapeutic potential of 5-ALA against lipotoxicity through redox pathway. MDPI 2023-06-15 /pmc/articles/PMC10299457/ /pubmed/37373300 http://dx.doi.org/10.3390/ijms241210151 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Hamada, Shintaro Mae, Yukari Takata, Tomoaki Hanada, Hinako Kubo, Misaki Taniguchi, Sosuke Iyama, Takuji Sugihara, Takaaki Isomoto, Hajime Five-Aminolevulinic Acid (5-ALA) Induces Heme Oxygenase-1 and Ameliorates Palmitic Acid-Induced Endoplasmic Reticulum Stress in Renal Tubules |
title | Five-Aminolevulinic Acid (5-ALA) Induces Heme Oxygenase-1 and Ameliorates Palmitic Acid-Induced Endoplasmic Reticulum Stress in Renal Tubules |
title_full | Five-Aminolevulinic Acid (5-ALA) Induces Heme Oxygenase-1 and Ameliorates Palmitic Acid-Induced Endoplasmic Reticulum Stress in Renal Tubules |
title_fullStr | Five-Aminolevulinic Acid (5-ALA) Induces Heme Oxygenase-1 and Ameliorates Palmitic Acid-Induced Endoplasmic Reticulum Stress in Renal Tubules |
title_full_unstemmed | Five-Aminolevulinic Acid (5-ALA) Induces Heme Oxygenase-1 and Ameliorates Palmitic Acid-Induced Endoplasmic Reticulum Stress in Renal Tubules |
title_short | Five-Aminolevulinic Acid (5-ALA) Induces Heme Oxygenase-1 and Ameliorates Palmitic Acid-Induced Endoplasmic Reticulum Stress in Renal Tubules |
title_sort | five-aminolevulinic acid (5-ala) induces heme oxygenase-1 and ameliorates palmitic acid-induced endoplasmic reticulum stress in renal tubules |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10299457/ https://www.ncbi.nlm.nih.gov/pubmed/37373300 http://dx.doi.org/10.3390/ijms241210151 |
work_keys_str_mv | AT hamadashintaro fiveaminolevulinicacid5alainduceshemeoxygenase1andamelioratespalmiticacidinducedendoplasmicreticulumstressinrenaltubules AT maeyukari fiveaminolevulinicacid5alainduceshemeoxygenase1andamelioratespalmiticacidinducedendoplasmicreticulumstressinrenaltubules AT takatatomoaki fiveaminolevulinicacid5alainduceshemeoxygenase1andamelioratespalmiticacidinducedendoplasmicreticulumstressinrenaltubules AT hanadahinako fiveaminolevulinicacid5alainduceshemeoxygenase1andamelioratespalmiticacidinducedendoplasmicreticulumstressinrenaltubules AT kubomisaki fiveaminolevulinicacid5alainduceshemeoxygenase1andamelioratespalmiticacidinducedendoplasmicreticulumstressinrenaltubules AT taniguchisosuke fiveaminolevulinicacid5alainduceshemeoxygenase1andamelioratespalmiticacidinducedendoplasmicreticulumstressinrenaltubules AT iyamatakuji fiveaminolevulinicacid5alainduceshemeoxygenase1andamelioratespalmiticacidinducedendoplasmicreticulumstressinrenaltubules AT sugiharatakaaki fiveaminolevulinicacid5alainduceshemeoxygenase1andamelioratespalmiticacidinducedendoplasmicreticulumstressinrenaltubules AT isomotohajime fiveaminolevulinicacid5alainduceshemeoxygenase1andamelioratespalmiticacidinducedendoplasmicreticulumstressinrenaltubules |