Lens proteasome shows enhanced rates of degradation of hydroxyl radical modified alpha-crystallin

Murakami, Katsuji; Jahngen, Jessica H.; Lin, Sharon; Davies, Kelvin J.A.; Taylor, Allen

doi:10.1016/0891-5849(90)90066-r

Cited by 72 publications

(22 citation statements)

References 23 publications

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“…The finding that treatment of rat liver proteins with AAPH leads to aggregation and formation of dityrosine derivatives of some proteins is analogous to the results of earlier studies (20,(26)(27)(28) showing that insoluble aggregates and dityrosine derivatives are formed by treatment of purified proteins with radiolytically generated ⅐OH. However, the mechanisms involved may be quite different since dityrosine formation and aggregation of proteins by the ⅐OH generating system occurs only in the absence of oxygen (26), whereas similar changes induced by the AAPH system occur only in the presence of oxygen.…”

Section: Discussionsupporting

confidence: 76%

Modification of protein surface hydrophobicity and methionine oxidation by oxidative systems

Chao

Ma²,

Stadtman³

1997

Proc. Natl. Acad. Sci. U.S.A.

289

192

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Aging and some pathological conditions are associated with the accumulation of altered (inactive or less active) forms of enzymes. It was suggested that these agerelated alterations ref lect spontaneous changes in protein conformation and͞or posttranslational modifications (e.g., oxidation). Because changes in protein conformations are often associated with changes in surface hydrophobicity, we have examined the effects of aging and oxygen radicaldependent oxidation on the hydrophobicity of rat liver proteins. As a measure of hydrophobicity, the increase in f luorescence associated with the binding of 8-anilino-1-naphthalene-sulfonic acid to hydrophobic regions on the proteins was used. By this criterion, the hydrophobicity of liver proteins of 24-month-old rats was 15% greater than that of 2-month-old animals. Exposure of liver proteins to a metal-catalyzed oxidation system (ascorbate͞Fe(II)͞H 2 O 2 ) or a peroxyl radical generating system, 2,2-azobis(2-amidinopropane) dihydrochloride (AAPH) led to increases of 2% or 30% in surface hydrophobicity, respectively. Treatment of liver proteins with the metal-catalyzed oxidation system led to a significant increase in reactive carbonyl content and to conversion of methionine residues to methionine sulfoxide residues. Treatment with AAPH led also to oxidation of methionine, tyrosine, and tryptophan residues and to the precipitation of some proteins. Dityrosine was detected in AAPH-treated protein, both the precipitate and supernatant fraction. The oxidation-dependent increase of hydrophobicity was correlated with an increase in the levels of methionine sulfoxide and dityrosine. These results suggest that oxidative modification of proteins may be responsible for the agerelated increase of protein surface hydrophobicity in vivo, and that the oxidation of methionine by an oxidative system may be an important event for the change of protein conformation.Covalent modification of proteins by oxidative systems have been implicated in various physiological and pathological conditions, such as aging, ischemia repurfusion and inflammatory disorders [for reviews, see Oliver et al. (1,2), and Stadtman (3, 4)]. These disorders are often associated with the accumulation of altered (inactive or less active) forms of various enzymes [for reviews, see Rothstein (5) and Oliver et al. (6)]. The age-related alterations may reflect spontaneous changes in protein conformations (7,8) or in protein oxidative modifications by reactive oxygen species (ROS) [for reviews, see Stadtman (9)]. The latter possibility is consistent with the facts that (i) many enzymes that accumulate as altered forms during aging are highly susceptible to modification by ROS; (ii) the ROS-mediated modifications of an enzyme can provoke changes in thermostability (10) and susceptibility to proteolytic degradation (10) similar to those that occur during aging (11); (iii) the level of oxidatively damaged protein, as measured by the presence of reactive carbonyl groups, increases with age (2). By whatever mechan...

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Section: Discussionsupporting

confidence: 76%

Modification of protein surface hydrophobicity and methionine oxidation by oxidative systems

Chao

Ma²,

Stadtman³

1997

Proc. Natl. Acad. Sci. U.S.A.

289

192

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“…In cell-free systems, the 20S proteasome can degrade oxidized proteins in a ubiquitin-independent manner (Paci®ci et al, 1989(Paci®ci et al, , 1993Murakami et al, 1990). Since none of the proteasome inhibitors can distinguish the 26S proteasome from the 20S proteasome, accumulation of oxidized proteins in the presence of proteasome inhibitor does not necessarily indicate the involvement of ubiquitination in their degradation.…”

Section: Carbonyl Containing Proteins Are Ubiquitinated In Cells and mentioning

confidence: 95%

Removal of Oxidatively Damaged Proteins from Lens Cells by the Ubiquitin-Proteasome Pathway

Shang

Nowell

Taylor

2001

Experimental Eye Research

Self Cite

105

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“…In lens homogenates, characterization of different proteolytic systems, especially the proteasome, has been the subject of many studies starting with reports from van Heyningens's group [9,12,[25][26][27][28][29]. Experimental results [5] have suggested that cataract formation may be linked to decreased activity of the proteasome leading to development of light-scattering aggregates, which thereby will destroy the transparency of the lens.…”

Section: Discussionmentioning

confidence: 99%

A New Model for Assessing Proteolysis in the Intact Mouse Lens in Organ Culture

et al. 2004

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Purpose: To develop a new method to investigate proteolysis in the intact lens in organ culture. Methods: Intact mouse lenses were assayed at regular intervals for proteolytic activity using fluorogenic peptide substrates ± addition of ionomycin. Specific inhibitors were used to determine the activity of calpains, the proteasome and acid lysosomal enzymes. Results: Significant levels of proteolytic activity were present in the intact lens. Proteolysis was stimulated by ionomycin. Preincubation with an inhibitor to the proteasome significantly decreased proteolysis whereas inhibitors of calpain and acid lysosomal enzymes did not. Conclusion: This study indicates that in the intact mouse lens in culture, the proteasome is an important protease. Its activity is at least partially regulated by calcium.

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Lens proteasome shows enhanced rates of degradation of hydroxyl radical modified alpha-crystallin

Cited by 72 publications

References 23 publications

Modification of protein surface hydrophobicity and methionine oxidation by oxidative systems

Modification of protein surface hydrophobicity and methionine oxidation by oxidative systems

Removal of Oxidatively Damaged Proteins from Lens Cells by the Ubiquitin-Proteasome Pathway

A New Model for Assessing Proteolysis in the Intact Mouse Lens in Organ Culture

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