Increased Prolylcarboxypeptidase Expression Can Serve as a Biomarker of Senescence in Culture

Nicholas Glen Boullard ¹, Jason J Paris ², Zia Shariat-Madar ²

⁰Jackson Hinds Comprehensive Health Center, Jackson, MS 39216, USA.

Molecules (basel, Switzerland) +

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May 25, 2024

View abstract on PubMed

Summary

Aging dysregulates prolylcarboxypeptidase (PRCP) in human pulmonary artery endothelial cells. Reduced PRCP impacts nitric oxide (NO) production and cellular respiration, highlighting its role in age-related vascular dysfunction.

Area Of Science

Biochemistry
Cell Biology
Aging Research

Background

Prolylcarboxypeptidase (PRCP) regulates angiotensin and kinin signaling, with elevated levels linked to chronic inflammatory diseases like cardiovascular disease (CVD) and diabetes.
Vascular endothelial cell senescence and mitochondrial dysfunction are key features of aging-related CVD.
Cellular senescence can alter lysosomal enzyme expression, but the effect on PRCP in aging remains unclear.

Purpose Of The Study

To investigate the impact of age-related cellular dysfunction on the expression and function of PRCP.
To characterize the PRCP-dependent prekallikrein (PK) pathway in human pulmonary artery endothelial cells (HPAECs) across different passages.

Main Methods

Kinetic analysis of HPAECs treated with high molecular weight kininogen (HK) and PK.
Assessment of PRCP and endothelial nitric oxide synthase (eNOS) expression and nitric oxide (NO) formation.
Measurement of telomerase reverse transcriptase mRNA levels and cellular respiration rates.

Main Results

Senescent HPAECs showed increased PRCP and eNOS expression and NO formation in early passages, which decreased in late passages.
Low PRCP activity in late-passage HPAECs correlated with reduced telomerase reverse transcriptase mRNA.
Increased passage number and reduced PRCP in HPAECs altered cellular respiration rates.

Conclusions

Aging dysregulates PRCP protein expression in HPAECs.
PRCP plays a role in age-related changes in NO production and cellular respiration.
Further research is needed to elucidate the complexity of the PRCP-dependent signaling pathway in aging.

Keywords:

cardiovascular dysfunction complex I inhibitor human telomerase reverse transcriptase kallikrein–kinin system metabolic syndrome renin–angiotensin system