ArticleThe Journal of clinical investigation2003
Inhibition of GAPDH activity by poly(ADP-ribose) polymerase activates three major pathways of hyperglycemic damage in endothelial cells.
Article in The Journal of clinical investigation, 2003. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 341 papers.
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Who cites it
341 citing papers in PubMed, 793 citations in OpenAlex.
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- Targeting Oxidative Stress and Mitochondrial Dysfunction in Diabetic Neuropathy: Mechanisms and Therapeutic Opportunities.Antioxidants (Basel, Switzerland) · 2026Review
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- The Central Role of Oxidative Stress in Diabetic Retinopathy: Advances in Pathogenesis, Diagnosis, and Therapy.Diagnostics (Basel, Switzerland) · 2026Review
- The diabetic retina-brain axis hypothesis in diabetic cognitive impairment: from pathophysiological mechanisms to therapeutic implications.Frontiers in endocrinology · 2026Review
- The Potential Connection Between Mechanical Stress and Heart Failure with Preserved Ejection Fraction: Mechanistic Insights and Therapeutic Potential.International journal of medical sciences · 2026Review
- Endothelial Metabolic Reprogramming Links Diabetes to Atherosclerosis.Diabetes, metabolic syndrome and obesity : targets and therapy · 2026Review
- Dysregulation of the Glycolytic Entry Gate and Survival Route by Advanced Lipoxidation End Products in Diabetes Mellitus.Journal of ophthalmology · 2026Article
- Molecular pathways of oxidative stress in diabetes: redox imbalance and insulin pathway dysregulation.Molecular biology reports · 2025Review
- Mechanisms of action of retinal microglia in diabetic retinopathy (Review).International journal of molecular medicine · 2025Review
- The mechanistic interplay of reactive oxygen species in metabolic pathways and insulin signaling in type 2 diabetes.Molecular biology reports · 2025Review
- Cysteine S-acetylation is a widespread post-translational modification on metabolic proteins.npj metabolic health and disease · 2025Article
- Application of Biomaterials in Diabetic Wound Healing: The Recent Advances and Pathological Aspects.Pharmaceutics · 2025Review
- Fenofibrate and Diabetic Retinopathy.Diabetes therapy : research, treatment and education of diabetes and related disorders · 2025Review
- High-density lipoproteins. Part 2. Impact of disease states on functionality.American journal of preventive cardiology · 2025Article
- Retinal Gatekeepers: Molecular Mechanism and Therapeutic Role of Cysteine and Selenocysteine.Biomolecules · 2025Review
281 more citing papers are in PubMed but not listed here.
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Authors and funding
7 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
In this report, we show that hyperglycemia-induced overproduction of superoxide by the mitochondrial electron transport chain activates the three major pathways of hyperglycemic damage found in aortic endothelial cells by inhibiting GAPDH activity. In bovine aortic endothelial cells, GAPDH antisense oligonucleotides activated each of the pathways of hyperglycemic vascular damage in cells cultured in 5 mM glucose to the same extent as that induced by culturing cells in 30 mM glucose. Hyperglycemia-induced GAPDH inhibition was found to be a consequence of poly(ADP-ribosyl)ation of GAPDH by poly(ADP-ribose) polymerase (PARP), which was activated by DNA strand breaks produced by mitochondrial superoxide overproduction. Both the hyperglycemia-induced decrease in activity of GAPDH and its poly(ADP-ribosyl)ation were prevented by overexpression of either uncoupling protein-1 (UCP-1) or manganese superoxide dismutase (MnSOD), which decrease hyperglycemia-induced superoxide. Overexpression of UCP-1 or MnSOD also prevented hyperglycemia-induced DNA strand breaks and activation of PARP. Hyperglycemia-induced activation of each of the pathways of vascular damage was abolished by blocking PARP activity with the competitive PARP inhibitors PJ34 or INO-1001. Elevated glucose increased poly(ADP-ribosyl)ation of GAPDH in WT aortae, but not in the aortae from PARP-1-deficient mice. Thus, inhibition of PARP blocks hyperglycemia-induced activation of multiple pathways of vascular damage.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.