Counteracting the enzymatic activity of dipeptidylpeptidase 4 for potential therapeutic advantage, with an emphasis on cord blood transplantation

Abstract

Dipeptidylpeptidase (DPP) 4, also known as CD26, is an enzyme present on the surface of a number of different cell types. It is also found within cells and as a soluble protein in body fluids. It can specifically truncate proteins at the penultimate N-terminus residue for some amino acids, such as alanine, proline, serine, and perhaps others. DPP4 has been implicated in regulating the in vitro and in vivo functional activities of a number of hematopoietically active molecules, and this information, along with that on inhibition of DPP4, has been studied in efforts to enhance hematopoietic cell transplantation (HCT), hematopoiesis after stress in mouse models, and in the clinical setting of single-unit cord blood (CB) HCT. This article reviews the current status of this compound's effects on regulatory proteins, the field of CB HCT, a potential role for modulating DPP4 activity in enhancing single-unit CB HCT in adults, and future aspects in context of other cellular therapies and the area of regenerative medicine.

What doesn't kill you makes you stranger: Dipeptidyl peptidase-4 (CD26) proteolysis differentially modulates the activity of many peptide hormones and cytokines generating novel cryptic bioactive ligands

“…It also has a soluble form (sCD26/DPP4) that can be found in the circulation and in various tissue compartments. DPP4 regulates the activity of many different chemokines and peptide hormones, and it acts by cleaving off N-terminus dipeptides typically with a penultimate alanine or proline, although under some conditions other amino acids may be targeted (Broxmeyer, 2013;Drucker, 2007;Mortier, et al, 2016).…”

The perceptions of natural compounds against dipeptidyl peptidase 4 in diabetes: from in silico to in vivo

“…15,31 Accordingly, sDPP-4 inhibition can improve success rate of transplantation after analyzing the relationship between sDPP-4 activity and hematopoietic stem cell transplantation. 32 The known DPP-4 (both soluble and membrane-bound forms) substrates include numerous homeostatic hormones such as GLP-1, NPY, glucagon, peptide Y, and secretin, which accurately regulate blood sugar homeostasis. 15 GLP-1 is involved in insulin sensitivity and secretion, food reward, and appetite through ghrelin and leptin, and cellular metabolism with adiponectin.…”