Varljen JadrankaSchool of Medicine; Department of Chemistry and Biochemistry; Brace Branchetta St. No. 20; HR-52000 Rijeka CroatiaPhone : +38551651135 Fax : Send E-Mail to Varljen Jadranka
Title: The effect of CD26-deficiency on dipeptidyl peptidase 8 and 9 expression profiles in a mouse model of Crohn's disease Buljevic S, Detel D, Pugel EP, Varljen J Ref: Journal of Cellular Biochemistry, 119:6743, 2018 : PubMed
The involvement of dipeptidyl peptidase (DP) IV/CD26 (DPP IV/CD26) family members in the pathogenesis of Crohn's disease (CD), an autoimmune inflammatory condition of the gut, is effected mainly through proteolytic cleavage of immunomodulatory substrates and DPP IV/CD26's costimulatory function. DP8 and DP9 are proteases with diverse functions including cell interactions, apoptosis, and immune response but their localization remains to be clarified. We assessed the impact of DPP IV/CD26 deficiency (CD26(-/-) ) on the expression profiles of DP8 and DP9 by qPCR and immunodetection as well as quantified DP8/9 enzyme activity in distinctive phases of a chemically-induced CD model in mice. CD26(-/-) did not affect colon DP8 mRNA expression, while the physiological concentration of DP8 protein is decreased in CD26(-/-) mice but rises in inflammation (P < 0.05). On the other hand, DP9 mRNA level is significantly increased in CD26(-/-) mice in inflammation as well as healing with the DP9 concentration being almost twofold increased (P < 0.05) in all experimental points in CD26(-/-) mice compared to wild-type indicating the expected up-regulation in CD26(-/-) conditions. Surprisingly, dominantly intracellular DP8 and DP9 were found in abundance in serum. DP8/9 activity is decreased in the inflamed colon, whereas its contribution to the overall serum DPP IV/CD26-like activity is negligible, suggesting the importance of their extra-enzymatic functions. To summarize, CD induction generated gene, protein and enzymatic changes of DP8 and DP9 so their involvement in inflammation development and/or healing process is implicated, especially in CD26(-/-) , and the question of their subcellular localization should be revised.
Fibromyalgia (FM) is a chronic pain syndrome with number of symptoms that present challenge in terms of diagnosis and treatment. Patients with FM show abnormal profile of purines in plasma. In this work, we measured serum activities of enzymes involved in purine metabolism, namely total adenosine deaminase (ADE) and its isoforms (ADE1 and ADE2), ecto-ATPase, and 5'-nucleotidase (5'-NT). We also measured activity of dipeptidyl peptidase IV (DPPIV) and prolyl endopeptidase (PEP). Spectrophotometric and fluorometric methods were used for enzyme activity determinations. Enzyme activities were measured in sera of 24 patients with FM that were not undergoing pharmacological treatment during the study. Control group comprised 32 healthy control subjects. Significantly higher activities of total ADE (P = 0.025) and ADE2 (P = 0.011) were observed in FM patients, while no significant differences in ADE1, ecto-ATPase, and 5'-NT activities (P > 0.05) were found when compared to healthy controls. Moreover, increase in the activity of DPPIV (P = 0.015) and lower activity of PEP (P = 0.011) were also found in the FM group. ROC analysis pointed to different diagnostic sensitivities/specificities for individual enzyme activities measured as follows: ADE (50.0/87.5), ADE2 (41.7/90.6), DPPIV (62.5/71.9), and PEP (83.3/62.5). ADE2 and PEP were shown to be independent predictors of FM, while combination of the two gives AUC of 0.786 (95 % confidence interval of 0.656-0.885, P < 0.05). Our results are showing that serum activities of ADE2 and PEP could be useful as biomarkers for FM diagnosis. However, relatively low diagnostic sensitivity of ADE2 and specificity of PEP must be taken into account.
        
Title: The influence of age on intestinal dipeptidyl peptidase IV (DPP IV/CD26), disaccharidases, and alkaline phosphatase enzyme activity in C57BL/6 mice Detel D, Baticic L, Varljen J Ref: Exp Aging Res, 34:49, 2008 : PubMed
The objective of this study was to determine and describe the age-related changes in intestinal brush border membrane enzyme activities that occur in C57Bl/6 mice. Specifically, jejunal, duodenal, and ileal dipeptidyl peptidase IV/CD26, disaccharidase (lactase, sucrase, and maltase), and alkaline phosphatase activities were determined. A significant correlation between analyzed intestinal brush border membrane enzyme activities and animal age was found. Our study revealed that intestinal dipeptidyl peptidase IV/CD26, lactase, sucrase, maltase, and alkaline phosphatase activities decline significantly with age (p < .05). Nevertheless, the horizontal (duodenum to ileum) enzyme activity patterns are not affected by age.
        
Title: Serum and intestinal dipeptidyl peptidase IV (DPP IV/CD26) activity in children with celiac disease Detel D, Persic M, Varljen J Ref: J Pediatr Gastroenterol Nutr, 45:65, 2007 : PubMed
OBJECTIVE: Dipeptidyl peptidase IV (DPP IV/CD26) is involved in the degradation of proline-rich proteins such as gliadin and in modulation of the immune response. The aim of this study was to examine the possible causal connection between DPP IV enzyme activities and celiac disease (CD) in children. PATIENTS AND METHODS: Intestinal mucosal biopsy specimens were obtained from 97 patients. The patients were divided into 3 groups: patients with active CD (n = 38), patients with malabsorption syndrome (MS) of other causes (n = 37), and control patients (n = 22). In addition, blood samples were collected from 48 patients with active CD and 50 control patients without gastrointestinal diseases. DPP IV enzyme activity was measured in the intestinal mucosal biopsy specimens and in the serum samples. RESULTS: DPP IV activity in the small intestine correlated inversely with the grade of mucosal damage in the CD (r = -0.92, P < 0.001) and MS groups (r = -0.90, P < 0.001). Intestinal DPP IV activity was statistically significantly lower in the CD and MS groups than in the control group (P < 0.001). By contrast, serum DPP IV activity was not significantly different between the CD and control groups. CONCLUSIONS: Our results suggest that the decrease in intestinal DPP IV activity is not specific to CD because it correlates with the level of mucosal damage in both patients with CD and those with MS. In addition, it seems that serum DPP IV activity cannot be used as a specific noninvasive diagnostic or prognostic marker of CD.