ArticleThe American journal of pathology2011
Tyrosine nitration of prostacyclin synthase is associated with enhanced retinal cell apoptosis in diabetes.
Article in The American journal of pathology, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 33 citations in OpenAlex.
- Diabetic retinopathy: shaped by the "hidden hand" of post-translational modifications.Molecular neurodegeneration · 2026Review
- Synergism of mechanisms underlying early-stage changes in retina function in male hyperglycemic db/db mice in the absence and presence of chemically-induced dyslipidemia.Scientific reports · 2023Article
- Emerging Roles of Dyslipidemia and Hyperglycemia in Diabetic Retinopathy: Molecular Mechanisms and Clinical Perspectives.Frontiers in endocrinology · 2021Review
- Autophagic degradation of KAT2A/GCN5 promotes directional migration of vascular smooth muscle cells by reducing TUBA/α-tubulin acetylation.Autophagy · 2020Article
- Inhibition of protein nitration prevents cisplatin-induced inactivation of STAT3 and promotes anti-apoptotic signaling in organ of Corti cells.Experimental cell research · 2019Article
- Mechanisms Underlying Early-Stage Changes in Visual Performance and Retina Function After Experimental Induction of Sustained Dyslipidemia.Neurochemical research · 2018Article
- High Glucose-Mediated Tyrosine Nitration of PI3-Kinase: A Molecular Switch of Survival and Apoptosis in Endothelial Cells.Antioxidants (Basel, Switzerland) · 2018Article
- Vitamin C Deficiency Reduces Muscarinic Receptor Coronary Artery Vasoconstriction and Plasma Tetrahydrobiopterin Concentration in Guinea Pigs.Nutrients · 2017Article
- Targeting nitrative stress for attenuating cisplatin-induced downregulation of cochlear LIM domain only 4 and ototoxicity.Redox biology · 2016Article
- Myeloperoxidase deletion prevents high-fat diet-induced obesity and insulin resistance.Diabetes · 2014Article
- Taurine prevents high glucose-induced angiopoietin-2/tie-2 system alterations and apoptosis in retinal microvascular pericytes.Molecular and cellular biochemistry · 2014Article
- Article
- Modified Lipoproteins in Diabetic Retinopathy: A Local Action in the Retina.Journal of clinical & experimental ophthalmology · 2013Article
- Article
- Retinal angiogenesis in the Ins2(Akita) mouse model of diabetic retinopathy.Investigative ophthalmology & visual science · 2013Article
- Serotonin 2B receptor (5-HT2B R) signals through prostacyclin and PPAR-ß/δ in osteoblasts.PloS one · 2013Article
- Diabetes-induced superoxide anion and breakdown of the blood-retinal barrier: role of the VEGF/uPAR pathway.PloS one · 2013Article
- Oxidative and endoplasmic reticulum stresses mediate apoptosis induced by modified LDL in human retinal Müller cells.Investigative ophthalmology & visual science · 2012Article
- Molecular mechanisms of diabetic retinopathy: potential therapeutic targets.Middle East African journal of ophthalmologyReview
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Authors and funding
6 authors at 2 institutions in 2 countries.
Funding
Abstract
The risk of diabetic retinopathy is associated with the presence of both oxidative stress and toxic eicosanoids. Whether oxidative stress actually causes diabetic retinopathy via the generation of toxic eicosanoids, however, remains unknown. The aim of the present study was to determine whether tyrosine nitration of prostacyclin synthase (PGIS) contributes to retinal cell death in vitro and in vivo. Exposure of human retinal pericytes to heavily oxidized and glycated LDL (HOG-LDL), but not native forms of LDL (N-LDL), for 24 hours significantly increased pericyte apoptosis, accompanied by increased tyrosine nitration of PGIS and decreased PGIS activity. Inhibition of the thromboxane receptor or cyclooxygenase-2 dramatically attenuated HOG-LDL-induced apoptosis without restoring PGIS activity. Administration of superoxide dismutase (to scavenge superoxide anions) or L-N(G)-nitroarginine methyl ester (L-NAME, a nonselective nitric oxide synthase inhibitor) restored PGIS activity and attenuated pericyte apoptosis. In Akita mouse retinas, diabetes increased intraretinal levels of oxidized LDL and glycated LDL, induced PGIS nitration, enhanced apoptotic cell death, and impaired blood-retinal barrier function. Chronic administration of tempol, a superoxide scavenger, reduced intraretinal oxidized LDL and glycated LDL levels, PGIS nitration, and retina cell apoptosis, thereby preserving the integrity of blood-retinal barriers. In conclusion, oxidized LDL-mediated PGIS nitration and associated thromboxane receptor stimulation might be important in the initiation and progression of diabetic retinopathy.
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