Identifying neuropeptide Y (NPY) as the main stress-related substrate of dipeptidyl peptidase 4 (DPP4) in blood circulation

Wagner, Leona; Kaestner, Florian; Wolf, Reinhard; Stiller, Harald; Heiser, Ulrich; Manhart, Susanne; Hoffmann, Torsten; Rahfeld, Jens‐Ulrich; Demuth, Hans‐Ulrich; Rothermundt, Matthias; Hörsten, Stephan von

doi:10.1016/j.npep.2016.02.007

Cited by 35 publications

(34 citation statements)

References 106 publications

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“…The decreased fibrinogen is usually associated with decreased coagulation31 but not with post-PCI bleeding32. It has been reported that the membrane-bound and soluble forms of DPP4 may have different levels of efficiency regarding their ability to cleave substrates3334. As fibrin is a DPP4 substrate35, the soluble form of DPP4 may truncate fibrin more easily than the membrane-bound form, leading to a negative correlation between DPP4a and fibrinogen.…”

Section: Discussionmentioning

confidence: 99%

Plasma DPP4 activity is associated with no-reflow and major bleeding events in Chinese PCI-treated STEMI patients

Li¹,

Chen²,

Chen³

et al. 2016

Sci Rep

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Dipeptidyl peptidase-4 (DPP4) is an important regulator of incretins and inflammation, and it is involved in the pathophysiological process of myocardial infarction (MI). This study investigated the role of plasma DPP4 activity (DPP4a) in patients with ST-segment elevation myocardial infarction (STEMI) who had undergone percutaneous coronary intervention (PCI). We recruited 747 consecutive PCI-treated STEMI patients from a tertiary referral center from January 2014 to October 2015. The outcomes of interest were the rates of no-reflow, in-hospital major adverse cardiac or cerebrovascular events (iMACCE), in-hospital complications (IHC) and in-hospital major bleeding. The DPP4a was lower in STEMI patients compared with the controls (p < 0.0001). Multivariate logistic-regression analyses (adjusted for confounding variables) showed that a 1 U/L increase in DPP4a was associated with an increased rate of no-reflow events (odds ratio [OR]: 1.07; 95% CI: 1.02–1.11; p < 0.01) and a decreased rate of major bleeding events (OR: 0.90; 95% CI: 0.82–0.98; p = 0.02). There were no associations between DPP4a and either iMACCE or IHC. In conclusions, high levels of DPP4a are independently associated with an increased rate of no-reflow events and a decreased rate of major bleeding events in PCT-treated STEMI patients.

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Section: Discussionmentioning

confidence: 99%

Plasma DPP4 activity is associated with no-reflow and major bleeding events in Chinese PCI-treated STEMI patients

Li¹,

Chen²,

Chen³

et al. 2016

Sci Rep

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“…The substrates reported include hormones, chemokines and several neuropeptides, such as substance P, neuropeptide Y, peptide YY, endomorphin‐1 and endomorphin‐2. Thus, the actions of these drugs might increase the levels of a variety of active peptides in vivo . On the other hand, DPP‐4 inhibitors also interact with other dipeptidyl peptidases including DPP‐8 and DPP‐9 .…”

Section: Discussionmentioning

confidence: 99%

Ineffectiveness of saxagliptin as a neuroprotective drug in 6-OHDA-lesioned rats

Turnes

Bassani

Souza

et al. 2018

Journal of Pharmacy and Pharmacology

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“…Previous studies demonstrated that enhancing NPY function boosts resilience (Christiansen et al, 2011; Southwick and Charney, 2012; Cohen et al, 2015). NPY can be served as a potential anti-depressive factor and used to monitor treatment of depression by recent findings (Bigio et al, 2016; Nakhate et al, 2016; Ozsoy et al, 2016; Wagner et al, 2016). NPY is one of the most abundant peptides in the central nervous system and mediates mood disorder, stress response and antidepressant effect mainly through the Y1 and Y2 receptors, which are densely expressed in the cortex, hippocampus and amygdala (Dumont et al, 1998; Price and Drevets, 2012).…”

Section: Discussionmentioning

confidence: 99%

The Role of Neuropeptide Y mRNA Expression Level in Distinguishing Different Types of Depression

Yue

Jiang

Yin

et al. 2016

Front. Aging Neurosci.

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Previous studies demonstrate that the protein of neuropeptide Y (NPY) is abnormal in depression patients, but the changes of NPY in different types of depression are unclear. This study was aimed to examine protein and mRNA expression levels of NPY in 159 cases with four groups including post-stroke depression (PSD) group, stroke without depression (Non-PSD) group, major depressive disorder (MDD) group and normal control (NC) group. The protein and gene expression analysis were performed by enzyme-linked immunosorbent assay (ELISA) and quantitative polymerase chain reaction-based methods. One way analysis of variance (ANOVA), chi-square tests and nonparametric test were used to evaluate general characteristics, clinical and biological materials. In order to explore the role of NPY in different types of depression, the partial correlations, binary logistic regression analysis and receiver operating characteristic (ROC) curve were calculated for PSD and MDD groups. There are significant differences of NPY protein (Fdf(3) = 5.167, P = 0.002) and mRNA expression levels (χKruskal2-Wallis, df(3) = 20.541, P < 0.001) among four groups. Bonferroni multiple comparisons found that the NPY protein was significantly decreased in PSD (FBonferroni = −7.133, P = 0.002) and Non-PSD group (FBonferroni = −5.612, P = 0.018) compared with NC group. However, contrasted with MDD group, the mRNA expression was increased in PSD and Non-PSD group by nonparametric test (all P < 0.05). In binary logistic analyses, NPY mRNA expression was independent predictors of PSD (odds ratio: 1.452, 95% CI, 1.081–1.951, P = 0.013). The ROC curve showed NPY mRNA had a general prognostic accuracy (area under the curve: 0.766, 95% CI, 0.656–0.876, P < 0.001). This is the first study to explore the distinguishing function of NPY in different types of depression. It will provide help in the identification of different subtypes of depression.

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Identifying neuropeptide Y (NPY) as the main stress-related substrate of dipeptidyl peptidase 4 (DPP4) in blood circulation

Cited by 35 publications

References 106 publications

Plasma DPP4 activity is associated with no-reflow and major bleeding events in Chinese PCI-treated STEMI patients

Plasma DPP4 activity is associated with no-reflow and major bleeding events in Chinese PCI-treated STEMI patients

Ineffectiveness of saxagliptin as a neuroprotective drug in 6-OHDA-lesioned rats

The Role of Neuropeptide Y mRNA Expression Level in Distinguishing Different Types of Depression

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