Xanthurenic acid provokes formation of unfolded proteins in endoplasmic reticulum of the lens epithelial cells.
The role of xanthurenic acid in a cell is unknown, but it is suspected to provoke several diseases. This study shows that accumulation of xanthurenic acid in the lens epithelial cells leads to an overexpression of endoplasmic reticulum (ER) resident stress chaperones proteins, glucose-regulated protein (Grp94), and calreticulin. Both chaperones proteins are overexpressed in the presence of unfolded proteins. A formation of the unfolded protein in the presence of xanthurenic acid may take place due to covalent binding of xanthurenic acid to protein. Grp94 is responsible for scavenging of the unfolded proteins. The results suggest that Grp94 scavenged xanthurenic acid-modified proteins, and for this reason become preferentially yellow-stained in the presence of yellow xanthurenic acid. Such a modified Grp94 is weakly recognized by anti-Grp94 antibody. An end point of the xanthurenic acid accumulation in the cell is the cell death. In conclusion xanthurenic acid can lead to cell pathology.
Malina
H Z
HZ
Department of Clinical and Experimental Research, University of Bern, Tiefenaustrasse 120, Bern, 3004, Switzerland. hmalina@hotmail.com
D000818:Animals; D002135:Calcium-Binding Proteins / Q000378:metabolism; D037282:Calreticulin; D002417:Cattle; D016923:Cell Death / Q000187:drug effects; D002478:Cells, Cultured; D003459:Crystallins / Q000737:chemistry* / Q000187:drug effects* / Q000378:metabolism; D004721:Endoplasmic Reticulum / Q000187:drug effects / Q000378:metabolism; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism; D018840:HSP70 Heat-Shock Proteins / Q000378:metabolism; D007908:Lens, Crystalline / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D008565:Membrane Proteins / Q000378:metabolism; D018832:Molecular Chaperones / Q000378:metabolism; D011485:Protein Binding; D011489:Protein Denaturation / Q000187:drug effects; D012261:Ribonucleoproteins / Q000378:metabolism; D013552:Swine; D014977:Xanthurenates / Q000378:metabolism / Q000494:pharmacology*
D002135:Calcium-Binding Proteins; D037282:Calreticulin; D003459:Crystallins; D018840:HSP70 Heat-Shock Proteins; D008565:Membrane Proteins; D018832:Molecular Chaperones; D012261:Ribonucleoproteins; D014977:Xanthurenates; C018551:glucose-regulated proteins; C028330:xanthurenic acid