We have earlier demonstrated that lutein effectively prevents hyperglycemia generated sustained oxidative stress in ARPE-19 cells by activating Nrf2 (nuclear factor erythroid 2-related factor 2) signaling. Since evidence portrays an intricate connection between ER (endoplasmic reticulum) stress and hyperglycemia-mediated oxidative stress, we aimed to explore the protective mechanism of lutein on hyperglycemia-induced ER stress in ARPE-19 cells. To determine the effect of lutein, we probed three major downstream branches of unfolded protein response (UPR) signaling pathways using western blot, immunofluorescent and RT-PCR techniques. The data showed a reduction (38%) in protein expression of an imperative ER chaperon, BiP (binding immunoglobulin protein), in glucose-treated ARPE-19 cells. At the same time, lutein pretreatment blocked this glucose-mediated effect, leading to a significant increase in BiP expression. Lutein promoted the phosphorylation of IRE1 (inositol requiring enzyme 1) and subsequent splicing of XBP1 (X-box binding protein 1), leading to enhanced nuclear translocation. Likewise, lutein activated the expression and translocation of transcription factors, ATF6 (activating transcription factor 6) and ATF4 (activating transcription factor 4) suppressed by hyperglycemia. Lutein also increased CHOP (C/EBP-homologous protein) levels in ARPE-19 cultured under high glucose conditions. The mRNA expression study showed that lutein pretreatment upregulates downstream UPR genes HRD1 (ERAD-associated E3 ubiquitin-protein ligase HRD1), p58 (protein kinase inhibitor p58) compared to high glucose treatment alone. From our study, it is clear that lutein show protection against hyperglycemia-mediated ER stress in ARPE-19 cells by activating IRE1-XBP1, ATF6, and ATF4 pathways and their downstream activators. Thus, lutein may have the pharmacological potential for protection against widespread disease conditions of ER stress.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1016/j.ejphar.2021.174663 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Ginsenoside Re suppresses high glucose-induced apoptosis of placental trophoblasts through endoplasmic reticulum stress-related CHOP/GADD153.
Hum Exp Toxicol
January 2025
Department of Gynecology and Obstetrics, Fuyong People's Hospital, Shenzhen, China.
Gestational diabetes mellitus (GDM) is a metabolic disorder that arises during pregnancy and heightens the risk of placental dysplasia. Ginsenoside Re (Re) may stabilize insulin and glucagon to regulate glucose levels, which may improve diabetes-associated diseases. This study aims to investigate the mechanism of Re in high glucose (HG)-induced apoptosis of trophoblasts through endoplasmic reticulum stress (ERS)-related protein CHOP/GADD153.
View Article and Find Full Text PDFInfluence of Ageing on the Pharmacodynamics and Pharmacokinetics of Chronically Administered Medicines in Geriatric Patients: A Review.
Clin Pharmacokinet
January 2025
Discipline of Pharmaceutical Sciences, School of Health Sciences, University of KwaZulu-Natal, Durban, South Africa.
As people age, the efficiency of various regulatory processes that ensure proper communication between cells and organs tends to decline. This deterioration can lead to difficulties in maintaining homeostasis during physiological stress. This includes but is not limited to cognitive impairments, functional difficulties, and issues related to caregivers which contribute significantly to medication errors and non-adherence.
View Article and Find Full Text PDFEffect of age-associated oxidative stress on sperm viability, acrosomal integrity and sperm apoptosis and DNA fragmentation in Sahiwal breeding bulls.
Vet Res Commun
January 2025
ARGO, ICAR- National Dairy Research Institute, Deemed University, Karnal, India.
Sperm motility is the prime functional attribute for semen quality and fertility of the bull. However, the bull's age directly affects the semen quality, and the bull's fertility and productive life decline with age. Even though research on age has been conducted in the past, it is still unclear how old a bull should be maintained at artificial insemination centers.
View Article and Find Full Text PDFUBIQUITIN-CONJUGATING ENZYME34 mediates pyrophosphatase AVP1 turnover and regulates abiotic stress responses in Arabidopsis.
Plant Physiol
January 2025
Institute of Biology, University of Graz, Graz, Austria.
Understanding the molecular mechanisms of abiotic stress responses in plants is instrumental for the development of climate-resilient crops. Key factors in abiotic stress responses, such as the proton- pumping pyrophosphatase (AVP1), have been identified, but their function and regulation remain elusive. Here, we explored the post-translational regulation of AVP1 by the ubiquitin-conjugating enzyme UBC34 and its relevance in the salt stress and phosphate starvation responses of Arabidopsis (Arabidopsis thaliana).
View Article and Find Full Text PDFE3 ligase substrate adaptor SPOP fine-tunes the UPR of pancreatic β cells.
Genes Dev
December 2024
Institute for Diabetes, Obesity, and Metabolism, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19146, USA;
The Cullin-3 E3 ligase adaptor protein SPOP targets proteins for ubiquitination and proteasomal degradation. We previously established the β-cell transcription factor (TF) and human diabetes gene PDX1 as an SPOP substrate, suggesting a functional role for SPOP in the β cell. Here, we generated a β-cell-specific deletion mouse strain ( ) and found that is necessary to prevent aberrant basal insulin secretion and for maintaining glucose-stimulated insulin secretion through impacts on glycolysis and glucose-stimulated calcium flux.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!