Transient elevation of temperature promotes cross-linking of α-crystallin-client proteins through formation of advanced glycation endproducts: A potential role in presbyopia and cataracts

The chaperone activity of alpha-crystallin is important for maintaining the transparency of the human lens. alpha B-crystallin (alpha BC) is a long-lived protein in the lens that accumulates chemical modifications during aging. The formation of advanced glycation end products (AGEs) through glycation is one such modification. alpha BC is a small heat shock protein that exhibits chaperone activity. We have previously shown that alpha BC-client protein complexes can undergo AGE-mediated interprotein cross-linking. Here, we demonstrate that short-term (1 h) exposure to elevated temperatures and methylglyoxal (MGO) during the chaperoning of client proteins by alpha BC promotes AGE-mediated interprotein cross-linking. Liquid chromatography/mass spectrometry (LC-MS/MS) analyses revealed the rapid formation of AGEs by MGO. Interestingly, we found that despite protein cross-linking, the chaperone activity of alpha BC increased during the transient elevation of temperature in the presence of MGO. Together, these results imply that transient and subtle elevation of temperature in the lens of the eye can promote protein cross-linking through AGEs, and if this phenomenon recurs over a period of many years, it could lead to early onset of presbyopia and age-related cataracts. (C) 2020 Elsevier Inc. All rights reserved.