ArticleAnnals of surgery2013
Poly-ADP-ribose-polymerase inhibition ameliorates hind limb ischemia reperfusion injury in a murine model of type 2 diabetes.
Article in Annals of surgery, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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15 citing papers in PubMed, 28 citations in OpenAlex.
- Hepatic GAPDH prevents excessive fasting-induced steatosis via serine-dependent inhibition of diacylglycerol synthesis.Cell death and differentiation · 2026Article
- PARP inhibitors target cellular energy metabolism: Mechanisms of action and clinical implications.Translational oncology · 2026Review
- SARS-CoV-2 N protein-induced Dicer, XPO5, SRSF3, and hnRNPA3 downregulation causes pneumonia.Nature communications · 2024Article
- Targeting protein modifications in metabolic diseases: molecular mechanisms and targeted therapies.Signal transduction and targeted therapy · 2023Review
- The Role of Poly(ADP-Ribose) Polymerase-1 in Cutaneous Wound Healing.Advances in wound care · 2019Review
- Remarks on the design and analyses of longitudinal studies for cancer patients with anorexia and weight loss.Journal of cachexia, sarcopenia and muscle · 2019Review
- Role of pseudohypoxia in the pathogenesis of type 2 diabetes.Hypoxia (Auckland, N.Z.) · 2019Article
- Does the Poly (ADP-Ribose) Polymerase Inhibitor Veliparib Merit Further Study for Cancer-Associated Weight Loss? Observations and Conclusions from Sixty Prospectively Treated Patients.Journal of palliative medicine · 2018Article
- Redox imbalance stress in diabetes mellitus: Role of the polyol pathway.Animal models and experimental medicine · 2018Article
- Pancreatic mitochondrial complex I exhibits aberrant hyperactivity in diabetes.Biochemistry and biophysics reports · 2017Article
- Sources and implications of NADH/NAD(+) redox imbalance in diabetes and its complications.Diabetes, metabolic syndrome and obesity : targets and therapy · 2016Review
- Hyperglycemic Stress and Carbon Stress in Diabetic Glucotoxicity.Aging and disease · 2016Review
- Protein Recognition in Drug-Induced DNA Alkylation: When the Moonlight Protein GAPDH Meets S23906-1/DNA Minor Groove Adducts.International journal of molecular sciences · 2015Review
- Rab2A is a pivotal switch protein that promotes either secretion or ER-associated degradation of (pro)insulin in insulin-secreting cells.Scientific reports · 2014Article
- Hind limb ischemia-reperfusion injury in diet-induced obese mice.The Journal of surgical research · 2014Article
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8 authors at 4 institutions in 1 country.
Funding
Abstract
introductionDiabetes is known to increase poly-ADP-ribose-polymerase (PARP) activity and posttranslational poly-ADP-ribosylation of several regulatory proteins involved in inflammation and energy metabolism. These experiments test the hypothesis that PARP inhibition will modulate hind limb ischemia reperfusion (IR) in a mouse model of type-II diabetes and ameliorate the ribosylation and the activity/transnuclear localization of the key glycolytic enzyme glyceraldehyde-3-phosphate dehydrogenase (GAPDH).
methodsdb/db mice underwent 1.5 hours of hind limb ischemia followed by 1, 7, or 24 hours of reperfusion. The treatment group received the PARP inhibitor PJ34 (PJ34) over a 24-hour period; the untreated group received Lactated Ringer (LR) at the same time points. IR muscles were analyzed for indices of PARP activity, fiber injury, metabolic activity, inflammation, GAPDH activity/intracellular localization, and poly-ADP-ribosylation of GAPDH.
resultsPARP activity was significantly lower in the PJ34-treated groups than in the Lactated Ringer group at 7 and 24 hours of reperfusion. There was significantly less muscle fiber injury in the PJ34-treated group than in the Lactated Ringer-treated mice at 24 hours of reperfusion. PJ34 lowered levels of select proinflammatory molecules at 7 hours and 24 hours of IR. There were significant increases in metabolic activity only at 24 hours of IR in the PJ34 group, which temporally correlated with increase in GAPDH activity, decreased GAPDH poly-ADP-ribosylation, and nuclear translocation of GAPDH.
conclusionsPJ34 reduced PARP activity, GAPDH ribosylation, and GAPDH translocation; ameliorated muscle fiber injury; and increased metabolic activity after hind limb IR injury in a murine model of type-II diabetes. PARP inhibition might be a therapeutic strategy after IR in diabetic humans.
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