Role of proteolysis in lenses: a review.
It has been suggested that proteases are involved in removal of damaged or obsolete proteins and/or that the activation of proteases could contribute to cataract formation. This review summarizes the properties of several recently studied lens endopeptidases including: trypsin-like protease, multicatalytic endopeptidase complex, membrane bound proteases, and calpain. Properties discussed include composition, substrate specificity, distribution, changes in activity during aging, and regulation. Additionally, properties of the lens ubiquitin conjugation system are reviewed. When possible, an attempt was made to relate these findings to whether the lens proteolytic activity was involved in clearing damaged proteins, or whether it could contribute to cataract formation. Clearing of damaged or obsolete lens proteins may involve the participation of several protease activities. Findings suggest that lens protease activities are lost at variable rates during aging, and differ in concentration between species. It was concluded that the consequence of proteolytic activity in the lens may depend closely on the compliment of proteolytic activities found. For instance, proteases causing only partial degradation of lens proteins may predominate in lenses undergoing cataract formation, while proteases assisting in the removal of partially degraded proteins are lost. The partially degraded lens proteins, as well as other denatured lens proteins, may then accumulate and lead to cataract formation.
David
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Department of Ophthalmology, School of Dentistry, Portland, OR 97201.
Shearer
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TR
D000375:Aging; D000818:Animals; D020346:Aquaporins; D002154:Calpain / Q000378:metabolism; D002352:Carrier Proteins / Q000378:metabolism; D002386:Cataract / Q000209:etiology; D002462:Cell Membrane / Q000201:enzymology; D003546:Cysteine Endopeptidases / Q000378:metabolism; D010450:Endopeptidases / Q000378:metabolism*; D005136:Eye Proteins / Q000378:metabolism; D006801:Humans; D007908:Lens, Crystalline / Q000201:enzymology*; D008025:Ligases; D008562:Membrane Glycoproteins; D009097:Multienzyme Complexes / Q000378:metabolism; D046988:Proteasome Endopeptidase Complex; D014357:Trypsin / Q000378:metabolism; D044763:Ubiquitin-Conjugating Enzymes
D020346:Aquaporins; D002352:Carrier Proteins; D005136:Eye Proteins; D008562:Membrane Glycoproteins; D009097:Multienzyme Complexes; C030328:aquaporin 0; C046288:ubiquitin carrier proteins; D044763:Ubiquitin-Conjugating Enzymes; D010450:Endopeptidases; D014357:Trypsin; D002154:Calpain; D003546:Cysteine Endopeptidases; D046988:Proteasome Endopeptidase Complex; D008025:Ligases