Prolyl carboxypeptidase activity in the circulation and its correlation with body weight and adipose tissue in lean and obese subjects

Kehoe, Kaat; Noels, Heidi; Theelen, Wendy; Hert, Emilie De; Xu, S.; Verrijken, An; Arnould, Thierry; Fransén, Erik; Hermans, Nina; Lambeir, Anne‐Marie; Gaal, Luc Van; Meester, Ingrid De

doi:10.1371/journal.pone.0197603

Cited by 8 publications

(23 citation statements)

References 37 publications

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“…Circulating PRCP mainly exists in white blood cells and plasma. The correlations between serum PRCP activity and various metabolic parameters, including body mass index and subcutaneous, abdominal, and visceral adipose tissues, have been confirmed (Kehoe et al, 2018). Our data indicate that plasma PRCP level and activity are elevated in AMI but not in unstable angina.…”

Section: Discussionsupporting

confidence: 74%

Prolylcarboxypeptidase Mitigates Myocardial Ischemia/Reperfusion Injury by Stabilizing Mitophagy

Hao

Liu

Guo

et al. 2020

Front. Cell Dev. Biol.

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The role of prolylcarboxypeptidase (PRCP) in myocardial ischemia/reperfusion (I/R) injury is unclear. Herein, we aimed to evaluate the protective effect of the PRCP-angiotensin-(1-7) [Ang-(1-7)]/bradykinin-(1-9) [BK-(1-9)] axis on myocardial I/R injury and identify the mechanisms involved. Plasma PRCP level and activity, as well as Ang-(1-7) and BK-(1-9) levels, were compared in healthy subjects, patients with unstable angina, and those with ST-segment-elevated acute myocardial infarction (AMI). Thereafter, the effects of PRCP overexpression and knockdown on left ventricular function, mitophagy, and levels of Ang-(1-7) and BK-(1-9) were examined in rats during myocardial I/R. Finally, the effects of Ang-(1-7) and BK-(1-9) on I/R-induced mitophagy and the signaling pathways involved were investigated in vitro in rat cardiomyocytes. AMI patients showed increased plasma level and activity of PRCP and levels of Ang-(1-7) and BK-(1-9) as compared with healthy subjects and those with unstable angina. PRCP protected against myocardial I/R injury in rats by paradoxical regulation of cardiomyocyte mitophagy during the ischemia and reperfusion phases, which was mediated by downstream Ang-(1-7) and BK-(1-9). We further depicted a possible role of activation of AMPK in mitophagy induction during ischemia and activation of Akt in mitophagy inhibition during reperfusion in the beneficial effects of Ang-(1-7) and BK-(1-9). Thus, the PRCP-Ang-(1-7)/BK-(1-9) axis may protect against myocardial I/R injury by paradoxical regulation of cardiomyocyte mitophagy during ischemia and reperfusion phases.

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Section: Discussionsupporting

confidence: 74%

Prolylcarboxypeptidase Mitigates Myocardial Ischemia/Reperfusion Injury by Stabilizing Mitophagy

Hao

Liu

Guo

et al. 2020

Front. Cell Dev. Biol.

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“…Significantly less (pyr)-apelin-13 (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12) was detected in PRCP-inhibited or PRCP/ACE2inhibited HUVEC after 24 h compared with control or ACE2-inhibited HUVEC. In the supernatants of all inhibitor-treated HAoEC, significantly less (pyr)-apelin-13 (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12) was observed after 24 h compared with the control group.…”

Section: Resultsmentioning

confidence: 91%

“…2.1. Cleavage of (Pyr)-Apelin-13 to (Pyr)-Apelin-13 (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12) Is PRCP-Dependent in HUVEC and PRCP-and ACE2-Dependent in HAoEC C-terminal cleavage of (pyr)-apelin-13 to (pyr)-apelin-13 (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12) in HUVEC and HAoEC (n = 4 per group) is shown in Figure 1 and is expressed as the ratio of the peak intensity of (pyr)-apelin-13 (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12) to the peak intensity of (pyr)-apelin-13 measured in the supernatant. The cleavage is significant after 24 h within all treatment groups in both types of endothelial cells, but is already observable after 8 h in control, PRCP-inhibited, and ACE2-inhibited HAoEC.…”

Section: Resultsmentioning

confidence: 99%

“…As there is still formation of (pyr)-apelin-13 (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12) after PRCP-inhibition in HUVEC or after PRCP/ACE2-inhibition in HAoEC, it is likely that also other enzymes are involved in this cleavage. As prolyl oligopeptidase (PREP, EC 3.4.21.26) cleaves after a proline, (pyr)apelin-13 is theoretically susceptible to C-terminal cleavage by PREP, but to the best of our knowledge PREP's putative contribution to this cleavage was never investigated previously.…”

Section: Stimulation With Pro-inflammatory Agents Revealed An Increase In Prcp Activity In the Supernatant Of Huvec And Haoecmentioning

confidence: 99%

“…PRCP has been implicated in the pathophysiology of hypertension and inflammation [5][6][7][8][9]. However, since Wallingford et al discovered that PRCP is responsible for inactivating the anorexigenic peptide alpha-melanocyte stimulating hormone 1-13 (α-MSH 1-13), PRCP mainly received interest for its role in metabolic disorders [10][11][12][13][14]. Both non-brain-penetrating and centrally active PRCP-inhibitors showed body weight reduction in diet-induced obesity in mice [15,16].…”

Section: Introductionmentioning

confidence: 99%

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Prolyl Carboxypeptidase Mediates the C-Terminal Cleavage of (Pyr)-Apelin-13 in Human Umbilical Vein and Aortic Endothelial Cells

Hert

Bracke

Pintelon

et al. 2021

IJMS

Self Cite

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The aim of this study was to investigate the C-terminal cleavage of (pyr)-apelin-13 in human endothelial cells with respect to the role and subcellular location of prolyl carboxypeptidase (PRCP). Human umbilical vein and aortic endothelial cells, pre-treated with prolyl carboxypeptidase-inhibitor compound 8o and/or angiotensin converting enzyme 2 (ACE2)-inhibitor DX600, were incubated with (pyr)-apelin-13 for different time periods. Cleavage products of (pyr)-apelin-13 in the supernatant were identified by mass spectrometry. The subcellular location of PRCP was examined via immunocytochemistry. In addition, PRCP activity was measured in supernatants and cell lysates of LPS-, TNFα-, and IL-1β-stimulated cells. PRCP cleaved (pyr)-apelin-13 in human umbilical vein and aortic endothelial cells, while ACE2 only contributed to this cleavage in aortic endothelial cells. PRCP was found in endothelial cell lysosomes. Pro-inflammatory stimulation induced the secretion of PRCP in the extracellular environment of endothelial cells, while its intracellular level remained intact. In conclusion, PRCP, observed in endothelial lysosomes, is responsible for the C-terminal cleavage of (pyr)-apelin-13 in human umbilical vein endothelial cells, while in aortic endothelial cells ACE2 also contributes to this cleavage. These results pave the way to further elucidate the relevance of the C-terminal Phe of (pyr)-apelin-13.

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Transcriptome-wide association study identifies novel genes associated with bone mineral density and lean body mass in children

Zeng

et al. 2022

Endocrine

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Objective To identify novel candidate genes whose expression is associated with bone mineral density (BMD) and body lean mass (LM) in children. Methods A tissue-specific transcriptome-wide association study (TWAS) was conducted utilizing a large-scale genome-wide association study (GWAS) dataset associated with BMD and LM and involving 10,414 participants. The measurement of BMD and LM phenotypes was made based on total-body dual-energy X-ray absorptiometry (TB-DXA) scans. TWAS was conducted by using FUSION software. Reference panels for muscle skeleton (MS), peripheral blood (NBL) and whole blood (YBL) were used for TWAS analysis. Functional enrichment and protein–protein interaction (PPI) analyses of the genes identified by TWAS were performed by using the online tool Metascape (http://metascape.org). Results For BMD, we identified 174 genes with P < 0.05, such as IKZF1 (P = 1.46 × 10−9) and CHKB (P = 8.31 × 10−7). For LM, we identified 208 genes with P < 0.05, such as COPS5 (P = 3.03 × 10−12) and MRPS33 (P = 5.45 × 10−10). Gene ontology (GO) enrichment analysis of the BMD-associated genes revealed 200 GO terms, such as protein catabolic process (Log P = −5.09) and steroid hormone-mediated signaling pathway (Log P = −3.13). GO enrichment analysis of the LM-associated genes detected 287 GO terms, such as the apoptotic signaling pathway (Log P = −8.08) and lipid storage (Log P = −3.55). Conclusion This study identified several candidate genes for BMD and LM in children, providing novel clues to the genetic mechanisms underlying the development of childhood BMD and LM.

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Prolyl carboxypeptidase activity in the circulation and its correlation with body weight and adipose tissue in lean and obese subjects

Cited by 8 publications

References 37 publications

Prolylcarboxypeptidase Mitigates Myocardial Ischemia/Reperfusion Injury by Stabilizing Mitophagy

Prolylcarboxypeptidase Mitigates Myocardial Ischemia/Reperfusion Injury by Stabilizing Mitophagy

Prolyl Carboxypeptidase Mediates the C-Terminal Cleavage of (Pyr)-Apelin-13 in Human Umbilical Vein and Aortic Endothelial Cells

Transcriptome-wide association study identifies novel genes associated with bone mineral density and lean body mass in children

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