Hormetic Heat Shock Enhances Autophagy through HSF1 in Retinal Pigment Epithelium Cells
To maintain homeostasis, cells have evolved stress-response pathways to cope with exogenous and endogenous stress factors. Diverse stresses at high doses may be detrimental, albeit low doses of stress, known as hormesis, can be beneficial. Upon exposure to stress, such as temperature rise, the conve...
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MDPI AG
2022-05-01
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Online Access: | https://www.mdpi.com/2073-4409/11/11/1778 |
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author | Mooud Amirkavei Flavia Plastino Anders Kvanta Kai Kaarniranta Helder André Ari Koskelainen |
author_facet | Mooud Amirkavei Flavia Plastino Anders Kvanta Kai Kaarniranta Helder André Ari Koskelainen |
author_sort | Mooud Amirkavei |
collection | DOAJ |
description | To maintain homeostasis, cells have evolved stress-response pathways to cope with exogenous and endogenous stress factors. Diverse stresses at high doses may be detrimental, albeit low doses of stress, known as hormesis, can be beneficial. Upon exposure to stress, such as temperature rise, the conventional heat shock response (HSR) regulated by the heat shock transcription factor 1 (HSF1) facilitates refolding of misfolded proteins with the help of heat shock proteins (HSPs). However, the role and molecular mechanisms underlying the beneficial effects of HSR with other clearance processes, such as autophagy, remain poorly understood. In this study, human ARPE-19 cells, an in vitro model of retinal pigment epithelium, were treated with hormetic heat shock (HHS) and the autophagy expression profile was examined using quantitative PCR (qPCR), immunoblotting, immunoprecipitation, and immunofluorescence. We demonstrate that HHS enhances the expression of fundamental autophagy-associated genes in ARPE-19 cells through the activation of HSF1. HHS transiently increases the level of SQSTM1 and LC3B-II and activates autophagy. These findings reveal a role for autophagic HSF1-regulated functions and demonstrate the contribution of autophagy to hormesis in the HSR by improving proteostasis. |
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issn | 2073-4409 |
language | English |
last_indexed | 2024-03-10T01:25:13Z |
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spelling | doaj.art-d63143acca3d462d9b424e15da73f0ec2023-11-23T13:52:36ZengMDPI AGCells2073-44092022-05-011111177810.3390/cells11111778Hormetic Heat Shock Enhances Autophagy through HSF1 in Retinal Pigment Epithelium CellsMooud Amirkavei0Flavia Plastino1Anders Kvanta2Kai Kaarniranta3Helder André4Ari Koskelainen5Department of Neuroscience and Biomedical Engineering, School of Science, Aalto University, 00076 Espoo, FinlandDepartment of Clinical Neuroscience, Division of Eye and Vision, St. Erik Eye Hospital, Karolinska Institutet, 17177 Stockholm, SwedenDepartment of Clinical Neuroscience, Division of Eye and Vision, St. Erik Eye Hospital, Karolinska Institutet, 17177 Stockholm, SwedenDepartment of Ophthalmology, Institute of Clinical Medicine, University of Eastern Finland and Kuopio University Hospital, 70210 Kuopio, FinlandDepartment of Clinical Neuroscience, Division of Eye and Vision, St. Erik Eye Hospital, Karolinska Institutet, 17177 Stockholm, SwedenDepartment of Neuroscience and Biomedical Engineering, School of Science, Aalto University, 00076 Espoo, FinlandTo maintain homeostasis, cells have evolved stress-response pathways to cope with exogenous and endogenous stress factors. Diverse stresses at high doses may be detrimental, albeit low doses of stress, known as hormesis, can be beneficial. Upon exposure to stress, such as temperature rise, the conventional heat shock response (HSR) regulated by the heat shock transcription factor 1 (HSF1) facilitates refolding of misfolded proteins with the help of heat shock proteins (HSPs). However, the role and molecular mechanisms underlying the beneficial effects of HSR with other clearance processes, such as autophagy, remain poorly understood. In this study, human ARPE-19 cells, an in vitro model of retinal pigment epithelium, were treated with hormetic heat shock (HHS) and the autophagy expression profile was examined using quantitative PCR (qPCR), immunoblotting, immunoprecipitation, and immunofluorescence. We demonstrate that HHS enhances the expression of fundamental autophagy-associated genes in ARPE-19 cells through the activation of HSF1. HHS transiently increases the level of SQSTM1 and LC3B-II and activates autophagy. These findings reveal a role for autophagic HSF1-regulated functions and demonstrate the contribution of autophagy to hormesis in the HSR by improving proteostasis.https://www.mdpi.com/2073-4409/11/11/1778autophagy-associated genesautophagosomesautolysosomesheat shock responseheat shock transcription factorhomeostasis |
spellingShingle | Mooud Amirkavei Flavia Plastino Anders Kvanta Kai Kaarniranta Helder André Ari Koskelainen Hormetic Heat Shock Enhances Autophagy through HSF1 in Retinal Pigment Epithelium Cells Cells autophagy-associated genes autophagosomes autolysosomes heat shock response heat shock transcription factor homeostasis |
title | Hormetic Heat Shock Enhances Autophagy through HSF1 in Retinal Pigment Epithelium Cells |
title_full | Hormetic Heat Shock Enhances Autophagy through HSF1 in Retinal Pigment Epithelium Cells |
title_fullStr | Hormetic Heat Shock Enhances Autophagy through HSF1 in Retinal Pigment Epithelium Cells |
title_full_unstemmed | Hormetic Heat Shock Enhances Autophagy through HSF1 in Retinal Pigment Epithelium Cells |
title_short | Hormetic Heat Shock Enhances Autophagy through HSF1 in Retinal Pigment Epithelium Cells |
title_sort | hormetic heat shock enhances autophagy through hsf1 in retinal pigment epithelium cells |
topic | autophagy-associated genes autophagosomes autolysosomes heat shock response heat shock transcription factor homeostasis |
url | https://www.mdpi.com/2073-4409/11/11/1778 |
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