دورية أكاديمية
Increased Prolylcarboxypeptidase Expression Can Serve as a Biomarker of Senescence in Culture
| العنوان: | Increased Prolylcarboxypeptidase Expression Can Serve as a Biomarker of Senescence in Culture |
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| المؤلفون: | Nicholas Glen Boullard, Jason J. Paris, Zia Shariat-Madar, Fakhri Mahdi |
| المصدر: | Molecules, Vol 29, Iss 10, p 2219 (2024) |
| بيانات النشر: | MDPI AG, 2024. |
| سنة النشر: | 2024 |
| المجموعة: | LCC:Organic chemistry |
| مصطلحات موضوعية: | cardiovascular dysfunction, metabolic syndrome, renin–angiotensin system, kallikrein–kinin system, human telomerase reverse transcriptase, complex I inhibitor, Organic chemistry, QD241-441 |
| الوصف: | Prolylcarboxypeptidase (PRCP, PCP, Lysosomal Pro-X-carboxypeptidase, Angiotensinase C) controls angiotensin- and kinin-induced cell signaling. Elevation of PRCP appears to be activated in chronic inflammatory diseases [cardiovascular disease (CVD), diabetes] in proportion to severity. Vascular endothelial cell senescence and mitochondrial dysfunction have consistently been shown in models of CVD in aging. Cellular senescence, a driver of age-related dysfunction, can differentially alter the expression of lysosomal enzymes due to lysosomal membrane permeability. There is a lack of data demonstrating the effect of age-related dysfunction on the expression and function of PRCP. To explore the changes in PRCP, the PRCP-dependent prekallikrein (PK) pathway was characterized in early- and late-passage human pulmonary artery endothelial cells (HPAECs). Detailed kinetic analysis of cells treated with high molecular weight kininogen (HK), a precursor of bradykinin (BK), and PK revealed a mechanism by which senescent HPAECs activate the generation of kallikrein upon the assembly of the HK–PK complex on HPAECs in parallel with an upregulation of PRCP and endothelial nitric oxide (NO) synthase (eNOS) and NO formation. The NO production and expression of both PRCP and eNOS increased in early-passage HPAECs and decreased in late-passage HPAECs. Low activity of PRCP in late-passage HPAECs was associated with rapid decreased telomerase reverse transcriptase mRNA levels. We also found that, with an increase in the passage number of HPAECs, reduced PRCP altered the respiration rate. These results indicated that aging dysregulates PRCP protein expression, and further studies will shed light into the complexity of the PRCP-dependent signaling pathway in aging. |
| نوع الوثيقة: | article |
| وصف الملف: | electronic resource |
| اللغة: | English |
| تدمد: | 29102219 1420-3049 |
| العلاقة: | https://www.mdpi.com/1420-3049/29/10/2219Test; https://doaj.org/toc/1420-3049Test |
| DOI: | 10.3390/molecules29102219 |
| الوصول الحر: | https://doaj.org/article/b74d598d5b8a44829589c111cff8df25Test |
| رقم الانضمام: | edsdoj.b74d598d5b8a44829589c111cff8df25 |
| قاعدة البيانات: | Directory of Open Access Journals |
Full Text Finder | تدمد: | 29102219 14203049 |
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| DOI: | 10.3390/molecules29102219 |