Lipid peroxidation in open‐angle glaucoma

Babizhayev, Mark A.; Bunin, A. Ya.

doi:10.1111/j.1755-3768.1989.tb01617.x

Cited by 69 publications

(104 citation statements)

References 24 publications

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“…Substantial aggregation of purified calpain-1 occurs even in the presence of micromolar concentrations of iso [4]LGE 2 (less than micromolar protein to molar iso [4]LGE 2 ratio). At non-physiological concentrations of iso [4]LGE 2 , the protein becomes highly aggregated and cannot enter the gel. Such aggregates are formed in physiological concentrations of iso [4]LGE 2 as well.…”

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confidence: 99%

“…This paradox is explicable by the fact that modification by isoLGs renders calpain-1 inactive. Thus, treatment of calpain-1 with iso [4]LGE 2 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]LGE 2 -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.…”

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confidence: 99%

“…Thus, treatment of calpain-1 with iso [4]LGE 2 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]LGE 2 -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 suggests 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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AbstractWe report that protein adducts of iso [4]levuglandin E 2 (iso [4]LGE 2 ), 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.

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confidence: 99%

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Isolevuglandin-Modified Proteins, Including Elevated Levels of Inactive Calpain-1, Accumulate in Glaucomatous Trabecular Meshwork

et al. 2007

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We report that protein adducts of iso [4]levuglandin E 2 (iso [4]LGE 2 ), 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 crosslinking. We found elevated levels of calpain-1 in glaucomatous TM. However, calpain activity in glaucomatous TM is only about 50% to 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]LGE 2 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]LGE 2 -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 suggests 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. KeywordsGlaucoma; Intraocular pressure; isolevuglandin; Primary open angle glaucoma; Retinal ganglion cell; Reactive oxygen species; Trabecular meshwork Glaucomas are a group of irreversible blinding neurodegenerative diseases that are late onset and progressive in nature. They are designated primary, when they occur without a known cause, or secondary, when onset can be attributed to any other illness or injury. World wide about 70 million people suffer from glaucoma 1 . Primary open angle glaucoma (POAG) is characterized by changes that reduce permeability of the trabecular meshwork (TM) tissue and consequently impede aqueous humor outflow resulting in elevated intraocular pressure (IOP). Mounting evidence supports the hypothesis that reactive oxygen species (ROS) play a pathogenic role in POAG 2 . Elevated levels of hydrogen peroxide in the aqueous humor promote TM degeneration and outflow resistance. Protection against the deleterious effects of ROS should be provided by the antioxidant activities of superoxide dismutase and glutathione Address Correspondence to: Sanjoy K. Bhattacharya, Bascom Palmer Eye, Institute, 1638 NW 10 th Avenue, Room 706A, University of Miami, Miami, FL,; E-mail: Sbhattacharya@med.miami.edu. NIH Public Access Author ManuscriptBiochemistry. Author manuscript; available in PMC 2009 January 15. Published in final edited form as:Biochemistry. 2008 January 15; 47(2): 817-825. doi:10.1021/bi701517m. NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author Manuscript peroxidase that are elevated in the aqueous humour of...

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Isolevuglandin-Modified Proteins, Including Elevated Levels of Inactive Calpain-1, Accumulate in Glaucomatous Trabecular Meshwork

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“…32) We therefore determined the level of lipid peroxidation, which is the hallmark of ROS-induced injury, by assessing the production of MDA in rat brains.…”

Section: Effect Of R Verniciflua Extract On Lipid Peroxidationmentioning

confidence: 99%

Preparative Isolation and Purification of Neuroprotective Compounds from <i>Rhus verniciflua</i> by High Speed Counter-Current Chromatography

Choi

Lee

et al. 2012

Biological & Pharmaceutical Bulletin

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In the present study, extracts from Rhus verniciflua were demonstrated to significantly attenuate the negative effects of hydrogen peroxide (H 2 O 2 ) on transformed retinal ganglion cell line (RGC-5 cells), indicating that they may be protective against oxidative stress-induced retinal degeneration. The inclusion of R. verniciflua in the culture was found to both reduce the levels of reactive oxygen species (ROS) present and lessen the up-regulation of apoptotic proteins such as cleaved poly(ADP-ribose) polymerase, cleaved caspase-3, and cleaved caspase-9. Active compounds were also successfully isolated from R. verniciflua using high-speed counter-current chromatography (HSCCC) with a two-phase solvent system composed of n-hexane-ethyl acetate-methanol-water (3.5 : 5 : 3.5 : 5, v/v). Using this method, we successfully separated 252.1 mg of fustin at a purity of over 93.09%, 51.2 mg of fisetin at a purity of over 95.45%, 39.7 mg of sulfuretin at a purity of over 95.17%, and 10.7 mg of butein at a purity of over 95.01% from 1.5 g of R. verniciflua extract. The chemical structures of these compounds were elucidated by chemical and spectral analyses. There isolated compounds also significantly attenuated the negative effects of H 2 O 2 on RGC-5 cells. Results therefore suggest that, due to its anti-oxidative and anti-apoptotic effects, R. verniciflua could be used as a lead substance for the treatment of retinal diseases such as glaucoma.

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Oxidative stress affects cytoskeletal structure and cell-matrix interactions in cells from an ocular tissue: The trabecular meshwork

1999

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The trabecular meshwork (TM) is a specialized eye tissue that regulates the aqueous humor outflow and controls intraocular pressure. Cells in this tissue are essential for maintenance of the outflow system. Disturbance of the TM cell status by insults such as oxidative stress may lead to elevation of the intraocular pressure and development of glaucoma. In the present study, we investigated the effect of oxidative stress on the adhesion of human TM cells to extracellular matrix (ECM) proteins. Treatment with 1 mM of H2O2 for 10 or 30 min did not affect cell viability, whereas the adhesion of TM cells to fibronectin, laminin, and collagen types I and IV was significantly reduced. Phalloidin and immunostaining also revealed reorganization of actin and vimentin structures. The level of integrins alpha5beta1, alphavbeta3, and beta1 was not altered, although the distribution of paxillin and focal adhesion kinase in focal contacts was reduced. Concomitantly, the level of transcription factor NF-kappaB was enhanced by the H2O2 treatment. Nuclear extracts of the treated cells also contained a heightened NF-kappaB binding activity. These changes persisted for up to 6 h after the H2O2 treatment but were partially recovered by 24 h. We concluded that under sublethal oxidative stress conditions, the TM cell adhesion to the ECM was impaired. The short-term loss of cell-matrix adhesiveness may be related to the rearrangement of cytoskeletal structures. Extensive and repeated oxidative stress in vivo may result in reduced TM cell adhesion, leading to cell loss, compromised TM integrity, and pathologic consequences.

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Lipid peroxidation in open‐angle glaucoma

Cited by 69 publications

References 24 publications

Isolevuglandin-Modified Proteins, Including Elevated Levels of Inactive Calpain-1, Accumulate in Glaucomatous Trabecular Meshwork

Isolevuglandin-Modified Proteins, Including Elevated Levels of Inactive Calpain-1, Accumulate in Glaucomatous Trabecular Meshwork

Preparative Isolation and Purification of Neuroprotective Compounds from <i>Rhus verniciflua</i> by High Speed Counter-Current Chromatography

Oxidative stress affects cytoskeletal structure and cell-matrix interactions in cells from an ocular tissue: The trabecular meshwork

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