Proline-Rich Cytokine from Neurosecretory Granules: A New Natural Substrate for Dipeptidyl Peptidase IV

Antonyan, Alvard; Sharoyan, Svetlana; Mardanyan, Sona; Galoyan, A. A.

doi:10.1007/s11064-010-0258-4

Cited by 6 publications

(4 citation statements)

References 15 publications

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“…CD26 is a multifunctional integral type II membrane glycoprotein, with a single transmembrane domain anchoring an extracellular catalytic domain with proteolytic activity (EC 3.4.14.5) to the membrane. As an enzyme, CD26 catalyzes the cleavage of dipeptides from the N‐terminus of polypeptides, with Pro or Ala at the penultimate position of different neuropeptides, hormones, vasoactive peptides, quimiocines, and a new natural proline‐rich cytokine . CD26 is widely expressed as a homodimer in most cell types, including T lymphocytes, on which it is a marker of activation .…”

Section: Cell Surface Ada As a Costimulatory Molecule With Implicatiomentioning

confidence: 99%

Moonlighting Adenosine Deaminase: A Target Protein for Drug Development

Cortés

Gracia

Moreno

et al. 2014

Medicinal Research Reviews

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Interest in adenosine deaminase (ADA) in the context of medicine has mainly focused on its enzymatic activity. This is justified by the importance of the reaction catalyzed by ADA not only for the intracellular purine metabolism, but also for the extracellular purine metabolism as well, because of its capacity as a regulator of the concentration of extracellular adenosine that is able to activate adenosine receptors (ARs). In recent years, other important roles have been described for ADA. One of these, with special relevance in immunology, is the capacity of ADA to act as a costimulator, promoting T-cell proliferation and differentiation mainly by interacting with the differentiation cluster CD26. Another role is the ability of ADA to act as an allosteric modulator of ARs. These receptors have very general physiological implications, particularly in the neurological system where they play an important role. Thus, ADA, being a single chain protein, performs more than one function, consistent with the definition of a moonlighting protein. Although ADA has never been associated with moonlighting proteins, here we consider ADA as an example of this family of multifunctional proteins. In this review, we discuss the different roles of ADA and their pathological implications. We propose a mechanism by which some of their moonlighting functions can be coordinated. We also suggest that drugs modulating ADA properties may act as modulators of the moonlighting functions of ADA, giving them additional potential medical interest.

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Section: Cell Surface Ada As a Costimulatory Molecule With Implicatiomentioning

confidence: 99%

Moonlighting Adenosine Deaminase: A Target Protein for Drug Development

Cortés

Gracia

Moreno

et al. 2014

Medicinal Research Reviews

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“…The kidney is a main site of expression of DPPIV, where it constitutes up to 14% of total membrane protein [17]. It is a highly specific serine protease with catalytic activity, but it can also function as a binding protein [18,19]. When associated with NHE3, the resulting oligomeric complex is exclusively distributed in microvilli of the BBM of the proximal tubule, where NHE3 is also active [13].…”

Section: Effect Of Serine Proteases On Na+ Transporting Proteins Of Tmentioning

confidence: 99%

Potential Role of Serine Proteases in Modulating Renal Sodium Transport in vivo

Jacquillet

Rubera²,

Unwin³

2011

Nephron Physiol

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The maintenance of sodium (Na⁺) homeostasis is an essential function of the kidney. It is achieved by a variety of transport processes localized all along the highly specialised segments of the nephron. Impairment of these transport mechanisms, and thereby Na⁺ handling, is associated with disturbed Na⁺ and water balance, leading to hypertension and oedema. This review focuses on the novel regulation of sodium reabsorption by serine proteases acting along the entire nephron.

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“…However, the peptide concentration in the blood decreased at day 2 post-injection to 3.111 ng/ml, similar to that found in the control, which was explained by proteolytic breakdown of the peptide. This assumption has been based on the recently revealed data indicating PRP-1 as a new natural substrate for DPPs (46) that are widely expressed on the surface of the lymphocytes in the blood plasma, substrates of which are chemokines, hormones, neuropeptides, and growth factors (47,48).…”

Section: Discussionmentioning

confidence: 99%

Morpho‑functional study of the hypothalamic proline‑rich polypeptide apoptotic activity against mouse Ehrlich ascites carcinoma

et al. 2020

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A new type of bioactive polypeptides of the neurosecretory hypothalamus called proline-rich peptides (PRPs), which are isolated from bovine neurosecretory granules of the neurohypophysis, are synthesized in the form of a common precursor protein (neurophysin vasopressin-associated glycoprotein). Proline-rich polypetide 1 (PRP-1; also known as galarmin) is comprised of 15 amino acids residues, and has been suggested to possess anti-neurodegenerative, immunoregulatory, hematopoietic, antimicrobial and antitumor properties. The cytostatic, antiproliferative effect of PRP-1 was demonstrated in the human chondrosarcoma JJ012 and triple negative breast carcinoma MDA MB 231 cell lines. PRP-1 action is disease and tissue specific. To further explore the antitumorigenic and possible cytotoxic effects of PRP-1, a morpho-functional study on the effect of PRP-1 on a mouse Ehrlich ascites carcinoma (EAC) model was conducted. The PRP-1-induced morphological features of EAC cells confirmed the apoptotic nature of PRP-1, as manifested by cell shrinkage, membrane blebbing, chromosome condensation (pyknosis) and nuclear fragmentation (karyorrhexis). The effect of PRP-1 on the number of tumor cells incubated for 24 h and their viability in trypan blue-stained samples lead to a 44% reduction in the number of viable cells on day 11 post-inoculation vs. 22% inhibition of viable cells after PRP-1 treatment (0.1 µg/ml) on day 7 post-inoculation. Apoptosis experiments using an Annexin V-cyanine 3 apoptosis detection kit indicated that 24 h incubation with 0.1 µg/ml PRP-1 caused a significant increase in the number of apoptotic cells, reaching 50.33%, compared to 8.33% in the sample control on day 7 post-inoculation.

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Proline-Rich Cytokine from Neurosecretory Granules: A New Natural Substrate for Dipeptidyl Peptidase IV

Cited by 6 publications

References 15 publications

Moonlighting Adenosine Deaminase: A Target Protein for Drug Development

Moonlighting Adenosine Deaminase: A Target Protein for Drug Development

Potential Role of Serine Proteases in Modulating Renal Sodium Transport in vivo

Morpho‑functional study of the hypothalamic proline‑rich polypeptide apoptotic activity against mouse Ehrlich ascites carcinoma

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