The release of prolylcarboxypeptidase delays endothelial cell function loss

Abstract

Prolylcarboxypeptidase (PRCP) is a risk factor for cardiovascular disease. Its functions are well-characterized. It is a critical factor for preserving cellular function by regulating angiotensin, prekallikrein, as well as des-Arg9-bradykinin, induced cell signaling. Several studies, including ours, provide evidence that PRCP levels influence vascular biology. An increased circulating level of PRCP is observed and is implemented in the pathogenesis of several chronic inflammatory diseases. The expression pattern and function of PRCP, a lysosomal serine protease, caused by long-time culture has not been thoroughly investigated. Brefeldin A (0.2 mM), an inhibitor of protein trafficking in the secretory pathway, was ineffective in blocking PRCP release, signifying that PRCP might be secreted via an uncharacterized exocytotic pathway. Cellular senescence, a driving force of age-related dysfunction, can differentially alter the expression of lysosomal enzymes. Here, two structurally distinct lysosomal enzymes, PRCP and SA β-galactosidase, were used to identify their expression pattern during the progression of senescence in endothelial cells. Increased expression of PRCP occurred in parallel to a decline in telomerase reverse transcriptase (hTERT) mRNA levels in the early stages of cellular senescence. However, independent of pH alterations, SA β-galactosidase expression was significantly ( P ≤ 0.5) higher in senescent cells compared to those in early-passage cells. Unlike SA β-galactosidase, expression and activity of PRCP was significantly ( P ≤ 0.5) declined in the later stages of cellular senescence. Our findings support the notion that PRCP potentially has a physiological role in delaying cellular senescence via suppressing reactive oxygen species production, endothelial cell function loss, and may have major implications on endothelial aging. Overhead account, University of Mississippi This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.