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: | , , , , |
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| Formato: | article |
| Lenguaje: | EN |
| Publicado: |
MDPI AG
2021
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| Materias: | |
| Acceso en línea: | https://doaj.org/article/c3eb87c5c69749b9baa075e6366c62ae |
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| Sumario: | 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. |
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