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Suppressing endoplasmic reticulum stress-related autophagy attenuates retinal light injury.

ABSTRACT: Excessive light exposure is a principal environmental factor, which can cause damage to photoreceptors and retinal pigment epithelium (RPE) cells and may accelerate the progression of age-related macular degeneration (AMD). In this study, oxidative stress, endoplasmic reticulum (ER) stress and autophagy caused by light exposure were evaluated in vitro and in vivo. Light exposure caused severe photo-oxidative stress and ER stress in photoreceptors (661W cells) and RPE cells (ARPE-19 cells). Suppressing either oxidative stress or ER stress was protective against light damage in 661W and ARPE-19 cells and N-acetyl-L-cysteine treatment markedly inhibited the activation of ER stress caused by light exposure. Moreover, suppressing autophagy with 3-methyladenine significantly attenuated light-induced cell death. Additionally, inhibiting ER stress either by knocking down PERK signals or with GSK2606414 treatment remarkably suppressed prolonged autophagy and protected the cells against light injury. In vivo experiments verified neuroprotection via inhibiting ER stress-related autophagy in light-damaged retinas of mice. In conclusion, the above results suggest that light-induced photo-oxidative stress may trigger subsequent activation of ER stress and prolonged autophagy in photoreceptors and RPE cells. Suppressing ER stress may abrogate over-activated autophagy and protect the retina against light injury.

SUBMITTER: Song JY

PROVIDER: S-EPMC7485697 | biostudies-literature | 2020 Aug

REPOSITORIES: biostudies-literature

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Suppressing endoplasmic reticulum stress-related autophagy attenuates retinal light injury.

Song Jing-Yao JY Fan Bin B Che Lin L Pan Yi-Ran YR Zhang Si-Ming SM Wang Ying Y Bunik Victoria V Li Guang-Yu GY

Aging 20200828 16

Excessive light exposure is a principal environmental factor, which can cause damage to photoreceptors and retinal pigment epithelium (RPE) cells and may accelerate the progression of age-related macular degeneration (AMD). In this study, oxidative stress, endoplasmic reticulum (ER) stress and autophagy caused by light exposure were evaluated <i>in vitro</i> and <i>in vivo</i>. Light exposure caused severe photo-oxidative stress and ER stress in photoreceptors (661W cells) and RPE cells (ARPE-19 ...[more]

PMID: 32858529

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Project description:ObjectiveThis study investigated the role of Mzb1 in puerarin protection against heart injury and dysfunction in acute myocardial infarction (AMI) mice.MethodsC57BL/6 mice were pretreated with and without puerarin at doses of 50 mg/kg and 100 mg/kg for 14 days before establishing the AMI model. An AMI model was induced by ligating the left descending anterior coronary artery, and AC16 cardiomyocytes were treated with H2O2 in vitro. Echocardiography was performed to measure cardiac function. DHE staining, nicotinamide adenine dinucleotide phosphate (NADPH) oxidase assay, and DCFH-DA oxidative fluorescence staining were used to determine reactive oxygen species (ROS) production in vivo and in vitro. Bioinformatics analysis was used to predict potential upstream transcription factors of Mzb1.ResultsPuerarin dose-dependently reduced myocardial infarction area and injury, accompanied by the improvement of cardiac function in AMI mice. AMI mice manifested an increase in myocardial oxidative stress, endoplasmic reticulum (ER) stress, apoptosis, and mitochondrial biogenesis dysfunction, which were inhibited by pretreatment with puerarin. Puerarin also prevented Mzb1 downregulation in the hearts of AMI mice or H2O2-treated AC16 cells. Consistent with the in vivo findings, puerarin inhibited H2O2-induced cardiomyocyte apoptosis, ER stress, and mitochondrial dysfunction, which were attenuated by siRNA Mzb1. Furthermore, the JASPAR website predicted that KLF4 may be a transcription factor for Mzb1. The expression of KLF4 was partially reversed by puerarin in the cardiomyocyte injury model, and KLF4 inhibitor (kenpaullone) inhibited Mzb1 expression and affected its function.ConclusionThese results suggest that puerarin can protect against cardiac injury by attenuating oxidative stress and endoplasmic reticulum stress through upregulating the KLF4/Mzb1 pathway and that puerarin may expand our armamentarium for the prevention and treatment of ischemic heart diseases.

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Suppressing endoplasmic reticulum stress-related autophagy attenuates retinal light injury.

Publications

Suppressing endoplasmic reticulum stress-related autophagy attenuates retinal light injury.

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