ArticleBiochemistry2008
Isolevuglandin-modified proteins, including elevated levels of inactive calpain-1, accumulate in glaucomatous trabecular meshwork.
Article in Biochemistry, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 29 citations in OpenAlex.
- Candidate Glaucoma Biomarkers: From Proteins to Metabolites, and the Pitfalls to Clinical Applications.Biology · 2021Review
- Isolevuglandins as mediators of disease and the development of dicarbonyl scavengers as pharmaceutical interventions.Pharmacology & therapeutics · 2020Review
- Molecular Structures of Isolevuglandin-Protein Cross-Links.Chemical research in toxicology · 2016Article
- Isolevuglandin adducts in disease.Antioxidants & redox signaling · 2015Review
- Mass spectrometry detection of isolevuglandin adduction to specific protein residues.Methods in molecular biology (Clifton, N.J.) · 2015Article
- Lipid peroxidation generates biologically active phospholipids including oxidatively N-modified phospholipids.Chemistry and physics of lipids · 2014Review
- Pretreatment with pyridoxamine mitigates isolevuglandin-associated retinal effects in mice exposed to bright light.The Journal of biological chemistry · 2013Article
- Posttranslational modification by an isolevuglandin diminishes activity of the mitochondrial cytochrome P450 27A1.Journal of lipid research · 2013Article
- Quantitative proteomics: TGFβ₂ signaling in trabecular meshwork cells.Investigative ophthalmology & visual science · 2011Article
- Isolevuglandins and mitochondrial enzymes in the retina: mass spectrometry detection of post-translational modification of sterol-metabolizing CYP27A1.The Journal of biological chemistry · 2011Article
- Decreased carbohydrate metabolism enzyme activities in the glaucomatous trabecular meshwork.Molecular vision · 2010Article
- Generation and biological activities of oxidized phospholipids.Antioxidants & redox signaling · 2010Review
- Isolevuglandins covalently modify phosphatidylethanolamines in vivo: detection and quantitative analysis of hydroxylactam adducts.Free radical biology & medicine · 2009Article
- Formation of gamma-ketoaldehyde-protein adducts during ethanol-induced liver injury in mice.Free radical biology & medicine · 2009Article
- Potential for transcriptional upregulation of cochlin in glaucomatous trabecular meshwork: a combinatorial bioinformatic and biochemical analytical approach.Investigative ophthalmology & visual science · 2009Article
- Increased isolevuglandin-modified proteins in glaucomatous astrocytes.Molecular vision · 2009Article
- The role of proteolytic cellular systems in trabecular meshwork homeostasis.Experimental eye research · 2009Review
- Cultured porcine trabecular meshwork cells display altered lysosomal function when subjected to chronic oxidative stress.Investigative ophthalmology & visual science · 2008Article
- Neuroprotection in glaucoma using calpain-1 inhibitors: regional differences in calpain-1 activity in the trabecular meshwork, optic nerve and implications for therapeutics.CNS & neurological disorders drug targets · 2008Review
- Technical Brief: a novel strategy for enrichment of trabecular meshwork protease proteome.Molecular vision · 2008Article
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
We report that protein adducts of iso[4]levuglandin E2 (iso[4]LGE2), a highly reactive product of free radical-induced lipid oxidation, accumulate in human glaucomatous trabecular meshwork (TM) but not in controls. Reactive oxygen species play a pathogenic role in primary open angle glaucoma by fostering changes that reduce permeability of the TM tissue and consequently impede aqueous humor outflow resulting in elevated intraocular pressure. IsoLGs covalently modify proteins and are especially effective in causing protein-protein cross-linking. We found elevated levels of calpain-1 in glaucomatous TM. However, calpain activity in glaucomatous TM is only about 50% of that in controls. This paradox is explicable by the fact that modification by isoLGs renders calpain-1 inactive. Thus, treatment of calpain-1 with iso[4]LGE2 in vitro results in covalent modification, inactivation, the formation of high molecular weight aggregates (as determined by Western and dynamic light scattering analyses), and resistance to proteasomal digestion. Iso[4]LGE2-modified calpain-1 undergoes ubiquitination, and its loading impairs the cellular proteasome activity, consistent with competitive inhibition and formation of suicidal high molecular weight aggregates. These data suggest that interference with proteasomal activity, owing to protein modification by isoLGs, could contribute to glaucoma pathophysiology by decreasing the ability of the TM to modulate outflow resistance.
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Registered trials
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