Glycation-induced inactivation of malate dehydrogenase protection by aspirin and a lens molecular chaperone, alpha-crystallin.
Non-enzymic glycosylation (glycation) of structural proteins has been widely studied as a possible mechanism in the long-term complications of diabetes. Here we show that glycation inactivates malate dehydrogenase. Aspirin affords some protection against the glycation, but alpha-crystallin, a lens protein which appears to act as a molecular chaperone in other systems, is much more effective. For example, 5 mM glucose completely inactivates malate dehydrogenase in four days, and 5 micrograms alpha-crystallin/ml provides complete protection against this inactivation. Fructose, a superior glycating agent, inactivates the enzyme in 24 hours but even so the same low concentration of alpha-crystallin is able to protect 80% of the activity. Other proteins provide no protection at the same concentration. The inactivation of malate dehydrogenase and other enzymes by glycation could play a role in diabetic complications, and molecular chaperones like alpha-crystallin could serve to protect them.
Heath
M M
MM
Nuffield Laboratory of Ophthalmology, University of Oxford, UK.
Rixon
K C
KC
Harding
J J
JJ
D000818:Animals; D001241:Aspirin / Q000494:pharmacology*; D002241:Carbohydrates / Q000494:pharmacology; D002386:Cataract / Q000209:etiology / Q000378:metabolism; D003459:Crystallins / Q000494:pharmacology* / Q000502:physiology; D048909:Diabetes Complications; D003920:Diabetes Mellitus / Q000378:metabolism; D006031:Glycosylation / Q000187:drug effects; D007052:Ibuprofen / Q000494:pharmacology; D007908:Lens, Crystalline / Q000378:metabolism*; D008291:Malate Dehydrogenase / Q000037:antagonists & inhibitors / Q000187:drug effects* / Q000378:metabolism; D018832:Molecular Chaperones / Q000494:pharmacology* / Q000502:physiology; D009124:Muscle Proteins / Q000037:antagonists & inhibitors / Q000187:drug effects / Q000378:metabolism; D009206:Myocardium / Q000201:enzymology; D011485:Protein Binding; D013552:Swine
D002241:Carbohydrates; D003459:Crystallins; D018832:Molecular Chaperones; D009124:Muscle Proteins; D008291:Malate Dehydrogenase; D001241:Aspirin; D007052:Ibuprofen