Objective: Viral infections contribute to the pathogenesis of type 1 diabetes. Viruses, or viral products such as double-stranded RNA (dsRNA), affect pancreatic beta-cell survival and trigger autoimmunity by unknown mechanisms. We presently investigated the mediators and downstream effectors of dsRNA-induced beta-cell death.
Research Design And Methods: Primary rat beta-cells and islet cells from wild-type, toll-like receptor (TLR) 3, type I interferon receptor (IFNAR1), or interferon regulatory factor (IRF)-3 knockout mice were exposed to external dsRNA (external polyinosinic-polycytidylic acid [PICex]) or were transfected with dsRNA ([PICin]).
Results: TLR3 signaling mediated PICex-induced nuclear factor-kappaB (NF-kappaB) and IRF-3 activation and beta-cell apoptosis. PICin activated NF-kappaB and IRF-3 in a TLR3-independent manner, induced eukaryotic initiation factor 2 alpha phosphorylation, and triggered a massive production of interferon (IFN)-beta. This contributed to beta-cell death, as islet cells from IFNAR1(-/-) or IRF-3(-/-) mice were protected against PICin-induced apoptosis.
Conclusions: PICex and PICin trigger beta-cell apoptosis via the TLR3 pathway or IRF-3 signaling, respectively. Execution of PICin-mediated apoptosis depends on autocrine effects of type I IFNs.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.2337/db07-0844 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Background/aims: Bruise is the extravasation of blood that may be mild or severe. Bone marrow mesenchymal stem cells (BM-MSCs) are one of the most promising cells used in regenerative medicine for treating many disorders. We aimed to evaluate the efficiency of BM-MSCs in treating cutaneous bruises.
View Article and Find Full Text PDFInvestigating the role of hyperexpressed HCN1 in inducing myocardial infarction through activation of the NF-κB signaling pathway.
Open Life Sci
December 2024
Department of Cardiology, The Third Affiliated Hospital of Zunyi Medical University (The First People's Hospital of Zunyi), Zunyi, 563000, Guizhou, People's Republic of China.
We investigated the protective effect of the NF-κB inhibitor, pyrrolidine dithiocarbamate (PDTC) on cardiomyocyte injury induced by HCN1 channel overexpression, and explored the underlying mechanisms. An HCN1 overexpression vector was constructed and transfected into H9C2 cells, followed by PDTC treatment. The experiments comprised the following groups: control, control + PDTC, overexpression negative control, HCN1 overexpression (HCN1-OE), and combined HCN1-OE + PDTC groups.
View Article and Find Full Text PDFPeroxisome Proliferator-Activated Receptor Gamma Coactivator-1-Alpha in Endometriosis: Expression, Regulation, and Potential Role.
Cureus
January 2025
Obstetrics and Gynecology, Affiliated People's Hospital of Fujian University of Traditional Chinese Medicine, Fuzhou, CHN.
Objective: The present study was designed to comprehensively analyze the expression profiles of peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α), estrogen-related receptor-α (ERRα), estrogen receptor-β (ERβ), interleukin-6 (IL-6), cysteinyl-aspartic acid-specific protease-3 (caspase-3), and cysteinyl-aspartic acid-specific protease-9 (caspase-9) in endometriosis tissues. It also aimed to elucidate the hitherto unclarified role of PGC-1α in the processes of proliferation, apoptosis, and gene expression regulation of human endometrial stromal cells, thereby providing novel insights and identifying potential molecular targets for advancing endometriosis treatment modalities.
Methods: A total of 49 ectopic endometrial tissue samples and 50 normal endometrial tissue samples were meticulously collected from patients who underwent gynecological surgeries in the People's Hospital Affiliated to Fujian University of Traditional Chinese Medicine in Fuzhou, China, between January 2022 and January 2023.
WT161, a selective HDAC6 inhibitor, decreases growth, enhances chemosensitivity, promotes apoptosis, and suppresses motility of melanoma cells.
Cancer Chemother Pharmacol
January 2025
Human Genetics Laboratory, Institute of Natural Sciences, Federal University of Alfenas (UNIFAL-MG), Alfenas, MG, 37130-001, Brazil.
Purpose: Histone deacetylase 6 (HDAC6) plays a critical role in tumorigenesis and tumor progression, contributing to proliferation, chemoresistance, and cell motility by regulating microtubule architecture. Despite its upregulation in melanoma tissues and cell lines, the specific biological roles of HDAC6 in melanoma are not well understood. This study aims to explore the functional effects and underlying mechanisms of WT161, a selective HDAC6 inhibitor, in melanoma cell lines.
View Article and Find Full Text PDFZinc Transporter 9 (ZnT9) Improves Obesity-Induced Asthenospermia by Attenuating Endoplasmic Reticulum Stress (ERS).
Biol Trace Elem Res
January 2025
Department of Physiology and Pathophysiology, School of Basic Medicine, Dali University, Dali, 671003, China.
The aim of this study was to explore the role of the ZnT9 protein in obesity-induced sperm maturation disorders in men. We generated a mouse model of obesity-induced weak spermatogenesis via a high-fat diet (HFD) for 10 weeks. In addition to the HFD, a 5-week intervention of salubrinal (SAL) (an inhibitor of endoplasmic reticulum stress) (1 mg/kg/day), ZnSO (15 mg/kg/day), and their combination was started at week 6, after which sperm viability and epididymal tissue damage were assessed.
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!