Differential Inhibition of Three Peptidase Activities of the Proteasome in Human Lens Epithelium by Heat and Oxidation

Andersson, My; Sjöstrand, Johan; Karlsson, Jens

doi:10.1006/exer.1999.0688

Cited by 28 publications

(13 citation statements)

References 38 publications

(48 reference statements)

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“…Evidence from previous studies showing partial reversal of peroxide-induced inhibition of chymotrypsin-like activity by DTT and the inhibition of chymotrypsin-like activity by sulfhydryl blocking compounds (Demasi et al, 2003;Andersson et al, 1999), suggest that at least one of the sites critical for maintenance of chymotrypsin-like activity is a cysteine residue. In fact, recent data suggests that the reversible S-glutathionylation of cysteine may be an important physiological regulator of the chymotrypsin-like activity (Demasi et al, 2001;Demasi et al, 2003).…”

Section: Mechanisms Of Chymotrypsin-like Inhibitionmentioning

confidence: 91%

“…Previous studies have shown oxidation or modification of a reactive cysteine residue can inhibit the chymotrypsin-like activity (Andersson et al, 1999;Demasi et al, 2003). To determine if there were age-dependent differences in the extent of reversible cysteine modification, we measured the chymotrypsin-like activity in the absence and presence of DTT.…”

Section: Inhibition Of Proteasome Activity With N-ethylmaleimidementioning

confidence: 99%

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Age-dependent inhibition of proteasome chymotrypsin-like activity in the retina

Kapphahn

Bigelow

Ferrington

2007

Experimental Eye Research

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The proteasome plays a fundamental role in processes essential for cell viability. A loss in proteasome function has been associated with aging, as well as a number of age-related diseases. Defining the mechanism(s) behind this loss in function will add important information regarding the molecular basis for aging. In the current study, we performed an age-based comparison of proteasome function and composition of subunits and regulatory proteins in the neural retina and retinal pigment epithelium (RPE) in Fischer 344 rats. In the RPE, there was no age-dependent difference in activity, subunit composition, or content of proteasome regulators, PA28 and PA700. In contrast, the aged neural retina demonstrated a significant reduction in the chymotrypsin-like activity and decreased degradation of both casein and casein modified by 4-hydroxynonenal. This loss in function could not be explained by differences in subunit composition, content of PA28 and PA700, or reversible modification of cysteine residues. To begin investigating the molecular basis for the age-associated decrement in proteasome function, we modified the cysteine residues in proteasome from young rats with the sulfhydryl reactive chemical N-ethylmaleimide. We observed inhibition of the chymotrypsin-like activity and decreased degradation of casein that was comparable to that seen in aged retinas. Thus, chemical modification of cysteine provides an in vitro method that partially recapitulates aging proteasome. Further studies are required to confirm irreversible modification of functionally significant cysteine as a potential mechanism behind the age-related loss in proteasome function.

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Section: Mechanisms Of Chymotrypsin-like Inhibitionmentioning

confidence: 91%

Section: Inhibition Of Proteasome Activity With N-ethylmaleimidementioning

confidence: 99%

Age-dependent inhibition of proteasome chymotrypsin-like activity in the retina

Kapphahn

Bigelow

Ferrington

2007

Experimental Eye Research

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“…The synthetic substrate LLVY can be cleaved by the proteasome and the calpains [11,[15][16][17]. In order to investigate the activity of these proteases in the intact mouse lens, the lenses were preincubated for 1 h with the proteasome inhibitor lactacystin, diluted to a final concentration of 10 ÌM from a 1 mM (H 2 O) stock solution or with the calpain inhibitor calpeptin, 50 ÌM (0.1% DMSO) or an inhibitor of acid lysosomal enzymes, monensin 10 ÌM (0.2% ethanol).…”

Section: Proteolytic Activity In the Mouse Lensmentioning

confidence: 99%

“…The involvement of these proteases in processes related to cataractogenesis has been shown for cultured cells [7], lens epithelial explants [8,9], cell lysates [6,10,11] and homogenized lenses [12]. An approach more similar to the in vivo situation is to monitor the protease systems in the intact lens with the proteases in their normal subcellular localization and the lens epithelium and lens fibers still intact.…”

Section: Introductionmentioning

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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“…Inhibitors specific to qertain 20S proteasome subunit are available commercially, which supports the possibility of Isubunit specific activity regulation (Kisselev and Goldberg 2001;Myung, Kim et al 2001;Kissel~v, Garcia-Calvo et al 2003). Several publications also report that proteasome activities carl be controlled in a subunit specific manner in certain phYSiological/pathological settings in Vfvo (Andersson, Sjostrand et al 1999;Bulteau, Lundberg et al 2001;Basset, Raymond et ~1. 2002).…”

Section: Regulation 0' Proteolytic Activities By Post-translational Mmentioning

confidence: 99%

Explore the murine cardiac 20S proteasomes : molecular composition and regulation.

Zong¹

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Differential Inhibition of Three Peptidase Activities of the Proteasome in Human Lens Epithelium by Heat and Oxidation

Cited by 28 publications

References 38 publications

Age-dependent inhibition of proteasome chymotrypsin-like activity in the retina

Age-dependent inhibition of proteasome chymotrypsin-like activity in the retina

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

Explore the murine cardiac 20S proteasomes : molecular composition and regulation.

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