These tools will no longer be maintained as of December 31, 2024. Archived website can be found here. PubMed4Hh GitHub repository can be found here. Contact NLM Customer Service if you have questions.


Pubmed for Handhelds

PUBMED FOR HANDHELDS

Search MEDLINE/PubMed

  • Title: Inflammation and apoptosis, two key events induced by hyperglycemia mediated reactive nitrogen species in RGC-5 cells.
    Author: Pal S, Rao GN, Pal A.
    Journal: Life Sci; 2021 Aug 15; 279():119693. PubMed ID: 34111464.
    Abstract:
    Nitrosative stress plays a critical role in retinal injury in high glucose (HG) environment of eye, but the mechanisms remain poorly understood. Here we tested the hypothesis that HG induced reactive nitrogen species (RNS) production acts as a key functional mediator of antioxidant depletion, mitochondrial dysfunction, biomolecule damage, inflammation and apoptosis. Our findings illustrated that exposure of cultured RGC-5 cells to HG significantly disrupts the antioxidant defense mechanism and mitochondrial machineries by increasing the loss of mitochondrial membrane potential (ΔѰM) and elevating mitochondrial mass. Furthermore, we used biochemical tools to analyze the changes in metabolites, sulfur amino acids (SAAs) such as L-glutathione (GSH) and L-cysteine (Cys), in the presence of HG environment. These metabolic changes were followed by an increase in glycolytic flux that is phosphofructokinase-2 (PFK-2) activity. Moreover, HG exposure results in a significant disruption of protein carbonylation (PC) and lipid peroxidation (LPO), downregulation of OGG1 and increase in 8-OHdG accumulations in RGC-5 cells. In addition, our results demonstrated that HG environment coinciding with increased expression of inflammatory mediators, cell cycle deregulation, decreased in cell viability and expression of FoxOs, increased lysosomal content leading to apoptosis. Pre-treatment of selective inhibitors of RNS significantly reduced the HG-induced cell cycle deregulation and apoptosis in RGC-5 cells. Collectively, these results illustrated that accumulated RNS exacerbates the antioxidant depletion, mitochondrial dysfunction, biomolecule damage, inflammation and apoptosis induced by HG exposure in RGC-5 cells. Treatment of pharmacological inhibitors attenuated the HG induced in retinal cells.
    [Abstract] [Full Text] [Related] [New Search]