Fibroblast activation protein (FAP, seprase, EC 3.4.21.B28) and dipeptidyl peptidase-IV (DPP-IV, CD26, EC 3.4.14.5) are homologous serine proteases implicated in the modulation of the bioavailability and thus the function of a number of biologically active peptides. In spite of their generally nonoverlapping expression patterns, DPP-IV and FAP are co-expressed and probably co-regulated in certain cell types suggesting that for some biological processes their functional synergy is essential. By an in situ enzymatic activity assay, we show an abundant DPP-IV-like enzymatic activity sensitive to a highly specific DPP-IV inhibitor sitagliptin and corresponding DPP-IV immunoreactivity in the adult human islets of Langerhans. Moreover, the homologous protease FAP was present in the human endocrine pancreas and was co-expressed with DPP-IV. DPP-IV and FAP were found in the pancreatic alpha cells as determined by the co-localization with glucagon immunoreactivity. In summary, we show abundant enzymatic activity of the canonical DPP-IV (CD26) in Langerhans islets in the natural tissue context and demonstrate for the first time the co-expression of FAP and DPP-IV in pancreatic alpha cells in adult humans. Given their ability to proteolytically modify several biologically active peptides, both proteases have the potential to modulate the paracrine signaling in the human Langerhans islets.

• MeSH
• buňky vylučující glukagon enzymologie   MeSH
• dipeptidylpeptidasa 4 analýza   MeSH
• dospělí MeSH
• endopeptidasy MeSH
• glukagon analýza   MeSH
• imunohistochemie MeSH
• konfokální mikroskopie MeSH
• Langerhansovy ostrůvky cytologie   enzymologie   MeSH
• lidé MeSH
• membránové proteiny analýza   MeSH
• serinové endopeptidasy analýza   MeSH
• želatinasy analýza   MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• dipeptidylpeptidasa 4 MeSH
• DPP4 protein, human MeSH Prohlížeč
• endopeptidasy MeSH
• fibroblast activation protein alpha MeSH Prohlížeč
• glukagon MeSH
• membránové proteiny MeSH
• serinové endopeptidasy MeSH
• želatinasy MeSH

Dipeptidyl peptidase-IV (DPP-IV) and fibroblast activation protein-α (FAP) are speculated to participate in the regulation of multiple biological processes, because of their unique enzymatic activity, as well as by non-hydrolytic molecular interactions. At present, the role of DPP-IV and FAP in the development and progression of various types of tumors, including glioblastoma, is intensively studied, and their functional crosstalk is hypothesized. In this article, we describe the correlative expression of DPP-IV and FAP mRNA in primary cell cultures derived from human glioblastoma and associated expression dynamics of both molecules in astrocytoma cell lines depending on culture conditions. Although the molecular mechanisms of DPP-IV and FAP co-regulations remain unclear, uncoupled expression of transgenic DPP-IV and the endogenous FAP suggests that it occurs rather at the transcriptional than at the posttranscriptional level. Understanding of the expressional and functional coordinations of DPP-IV and FAP may help clarify the mechanisms of biological roles of both molecules in transformed astrocytic cells.

• MeSH
• buněčná diferenciace MeSH
• buněčné extrakty chemie   MeSH
• buněčné kultury MeSH
• dipeptidylpeptidasa 4 genetika   metabolismus   MeSH
• endopeptidasy MeSH
• enzymatické testy MeSH
• genetická transkripce * MeSH
• lidé MeSH
• membránové proteiny genetika   metabolismus   MeSH
• messenger RNA genetika   metabolismus   MeSH
• neuroglie enzymologie   metabolismus   MeSH
• rekombinantní proteiny genetika   metabolismus   MeSH
• serinové endopeptidasy genetika   metabolismus   MeSH
• transformované buněčné linie MeSH
• želatinasy genetika   metabolismus   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• buněčné extrakty MeSH
• dipeptidylpeptidasa 4 MeSH
• endopeptidasy MeSH
• fibroblast activation protein alpha MeSH Prohlížeč
• membránové proteiny MeSH
• messenger RNA MeSH
• rekombinantní proteiny MeSH
• serinové endopeptidasy MeSH
• želatinasy MeSH

Several of the proinflammatory peptides involved in rheumatoid arthritis pathogenesis, including peptides induced downstream of tumor necrosis factor-alpha as well as the monocyte/T cell-attracting chemokines RANTES and stromal cell-derived factor (SDF)-1alpha and the neuropeptides vasoactive intestinal peptide (VIP) and substance P, have their biological half-lives controlled by dipeptidyl peptidase IV (DPPIV). Proteolysis by DPPIV regulates not only the half-life but also receptor preference and downstream signaling. In this article, we examine the role of DPPIV homologs, including CD26, the canonical DPPIV, and their substrates in the pathogenesis of rheumatoid arthritis. The differing specific activities of the DPPIV family members and their differential inhibitor response provide new insights into therapeutic design.

• MeSH
• dipeptidylpeptidasa 4 chemie   metabolismus   MeSH
• inhibitory proteas MeSH
• izoenzymy MeSH
• katalytická doména MeSH
• lidé MeSH
• myši MeSH
• peptidy metabolismus   MeSH
• revmatoidní artritida enzymologie   etiologie   patologie   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH
• Názvy látek
• dipeptidylpeptidasa 4 MeSH
• inhibitory proteas MeSH
• izoenzymy MeSH
• peptidy MeSH