The emerging role of dipeptidyl peptidase 3 in pathophysiology

Malovan, Grazia; Hierzberger, Bettina; Suraci, Samuele; Schaefer, Maximillian; Santos, Karine; Jha, Shalinee; Macheroux, Peter

doi:10.1111/febs.16429

Cited by 17 publications

(15 citation statements)

References 120 publications

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“…The most notable DPP3 substrate is angiotensin II (Ang II), which serves as the primary effector molecule of the renin–angiotensin–aldosterone system (RAAS). The RAAS plays a vital role in regulating the cardiovascular system homeostasis, modulating blood pressure through the sympathetic system, glomerular filtration, releasing endogenous catecholamine and vasopressin, and stimulating vascular smooth muscle cells [ 20 , 21 ].…”

Section: Introductionmentioning

confidence: 99%

Dipeptidyl Amino-Peptidase 3 (DPP3) as an Early Marker of Severity in a Patient Population with Cardiogenic Shock

et al. 2023

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Dipeptidyl amino-peptidase 3 (DPP3) is an aminopeptidase that is released into circulation upon cell death. DPP3 is involved in the degradation of angiotensins, enkephalines, and endomorphines. It has been shown that circulating DPP3 (cDPP3) plasma concentration increases in cardiogenic shock (CS) patients and correlates with high mortality risk. Cardiogenic shock is a life-threatening syndrome associated with organ hypoperfusion. One of the common causes of CS is acute myocardial infarction (AMI). This study aimed to investigate if cDPP3 levels are associated with CS severity and the need for ventilation in patients suffering from CS. Fifteen patients with CS were included in this study. Six patients were invasively ventilated. The values of cDPP3 were higher in ventilated patients than in non-ventilated patients at admission, 3 h, and 24 h after admission in the intensive care unit. Patients with pulmonary hypertension at admission also showed high cDPP3 values at all time points. Furthermore, high cDPP3 levels were associated with reduced stroke volume. Our results suggest that cDPP3 could predict CS progression and guide therapy escalation.

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Section: Introductionmentioning

confidence: 99%

Dipeptidyl Amino-Peptidase 3 (DPP3) as an Early Marker of Severity in a Patient Population with Cardiogenic Shock

et al. 2023

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“…Hypotheses supporting their hypotensive effects were also published [90][91][92][93]. On the other hand, orthologous proteins of the dipeptidases, aminopeptidases, dipeptidyl peptidase, and serine carboxypeptidase (Table 2) have a consolidated biological role as processing enzymes [94][95][96][97].…”

Section: Discussionmentioning

confidence: 98%

Extracellular Vesicles from Bothrops jararaca Venom Are Diverse in Structure and Protein Composition and Interact with Mammalian Cells

Machado

Verçoza

Nogueira

et al. 2022

Toxins

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Snake venoms are complex cocktails of non-toxic and toxic molecules that work synergistically for the envenoming outcome. Alongside the immediate consequences, chronic manifestations and long-term sequelae can occur. Recently, extracellular vesicles (EVs) were found in snake venom. EVs mediate cellular communication through long distances, delivering proteins and nucleic acids that modulate the recipient cell’s function. However, the biological roles of snake venom EVs, including possible cross-organism communication, are still unknown. This knowledge may expand the understanding of envenoming mechanisms. In the present study, we isolated and characterized the EVs from Bothrops jararaca venom (Bj-EVs), giving insights into their biological roles. Fresh venom was submitted to differential centrifugation, resulting in two EV populations with typical morphology and size range. Several conserved EV markers and a subset of venom related EV markers, represented mainly by processing enzymes, were identified by proteomic analysis. The most abundant protein family observed in Bj-EVs was 5’-nucleotidase, known to be immunosuppressive and a low abundant and ubiquitous toxin in snake venoms. Additionally, we demonstrated that mammalian cells efficiently internalize Bj-EVs. The commercial antibothropic antivenom partially recognizes Bj-EVs and inhibits cellular EV uptake. Based on the proteomic results and the in vitro interaction assays using macrophages and muscle cells, we propose that Bj-EVs may be involved not only in venom production and processing but also in host immune modulation and long-term effects of envenoming.

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“…Despite the attention gained by Dpp3 since its discovery at the end of the 1960s [13], several aspects related to its function remain elusive [14]. For example, a poorly investigated topic is Dpp3 function in the context of bone biology, which has been addressed only recently by Menale et al, who showed that the absence of Dpp3 in the mouse model Dpp3 KO caused bone loss owing to increased osteoclast activity and impaired bone quality, particularly in female mice after ovariectomy [7].…”

Section: Discussionmentioning

confidence: 99%

Dipeptidyl Peptidase 3 Activity as a Promising Biomarker of Bone Fragility in Postmenopausal Women

et al. 2022

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The dipeptidyl peptidase 3 (Dpp3) is a ubiquitous zinc-dependent aminopeptidase, participating in the activation or degradation of signaling peptides and in the Keap1–Nrf2 antioxidant pathway. The absence of Dpp3 in the Dpp3 knockout mouse model causes increased osteoclast activity, altered osteogenic function, sustained oxidative stress in the bone tissue, and bone loss. We aimed to assess the association of Dpp3 activity with bone fragility in postmenopausal osteoporosis and the impact of denosumab on enzymatic activity. We conducted a two-phase study including 69 postmenopausal women with severe osteoporosis and 36 postmenopausal women without osteometabolic conditions, as controls (cross-sectional phase). Subjects with severe osteoporosis were assessed at baseline and 14 days after the first denosumab administration (prospective phase). The results showed significant reduction in serum Dpp3 activity (expressed as nmoles of formed product/mg proteins/min) in patients vs. controls (0.791 ± 0.232 vs. 1.195 ± 0.338; p < 0.001), and significant association with bone mass at the femoral neck (r = 0.28, p = 0.02) in patients prior to treatment. We found a negative correlation between C-terminal telopeptide (CTX) or N-terminal pro-peptide of type 1 procollagen (P1NP) levels and Dpp3 activity (respectively, r = −0.29, p = 0.012; and r = −0.2572, p = 0.033). Dpp3 activity did not change after denosumab injection. Our findings support a critical role played by Dpp3 in bone homeostasis as a potential bone protective factor. Additional clinical studies in larger cohorts might explore the implementation of Dpp3 assessment as a biomarker of bone health status.

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The emerging role of dipeptidyl peptidase 3 in pathophysiology

Cited by 17 publications

References 120 publications

Dipeptidyl Amino-Peptidase 3 (DPP3) as an Early Marker of Severity in a Patient Population with Cardiogenic Shock

Dipeptidyl Amino-Peptidase 3 (DPP3) as an Early Marker of Severity in a Patient Population with Cardiogenic Shock

Extracellular Vesicles from Bothrops jararaca Venom Are Diverse in Structure and Protein Composition and Interact with Mammalian Cells

Dipeptidyl Peptidase 3 Activity as a Promising Biomarker of Bone Fragility in Postmenopausal Women

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