Department of Biochemistry and Mass Spectrometry Research Center, Vanderbilt University School of Medicine, Nashville, TN 37232, USA.
Cells. 2022 Dec 14;11(24):4042. doi: 10.3390/cells11244042.
Age-related protein truncation is a common process in long-lived proteins such as proteins found in the ocular lens. Major truncation products have been reported for soluble and membrane proteins of the lens, including small peptides that can accelerate protein aggregation. However, the spatial localization of age-related protein fragments in the lens has received only limited study. Imaging mass spectrometry (IMS) is an ideal tool for examining the spatial localization of protein products in tissues. In this study we used IMS to determine the spatial localization of small crystallin fragments in aged and cataractous lenses. Consistent with previous reports, the pro-aggregatory αA-crystallin 66-80 peptide as well as αA-crystallin 67-80 and γS-crystallin 167-178 were detected in normal lenses, but found to be increased in nuclear cataract regions. In addition, a series of γS-crystallin C-terminal peptides were observed to be mainly localized to cataractous regions and barely detected in transparent lenses. Other peptides, including abundant αA3-crystallin peptides were present in both normal and cataract lenses. The functional properties of these crystallin peptides remain unstudied; however, their cataract-specific localization suggests further studies are warranted.
年龄相关的蛋白截断是一种常见的过程，在长寿蛋白中，如在眼晶状体中发现的蛋白质。已报道了晶状体可溶性和膜蛋白的主要截断产物，包括可以加速蛋白聚集的小肽。然而，年龄相关的蛋白片段在晶状体中的空间定位只受到了有限的研究。成像质谱（IMS）是研究组织中蛋白产物空间定位的理想工具。在这项研究中，我们使用 IMS 来确定老年和白内障晶状体中小结晶蛋白片段的空间定位。与之前的报道一致，促聚集的 αA-晶体蛋白 66-80 肽以及 αA-晶体蛋白 67-80 和 γS-晶体蛋白 167-178 被检测到在正常晶状体中，但在核性白内障区域中发现增加。此外，一系列 γS-晶体蛋白 C 末端肽被观察到主要定位于白内障区域，在透明晶状体中几乎检测不到。其他肽，包括丰富的 αA3-晶体蛋白肽，存在于正常和白内障晶状体中。这些晶体蛋白肽的功能特性尚未研究；然而，它们在白内障中的特异性定位表明需要进一步研究。
