Distribution of Proline-Specific Aminopeptidases in Human Tissues and Body Fluids

Abstract

The proline-specific peptidases, aminopeptidase P (EC 3.4.11.9) and dipeptidyl peptidase IV (EC 3.4.14.5), were measured in human tissue homogenates and physiological fluids. All tissues examined contained measurable aminopeptidase P and dipeptidyl peptidase IV activities. High specific activities for both enzymes under study were found in benign prostatic hypertrophy. Normal prostate and prostatic adenocarcinoma had a much lower activity. This difference, however, is not reflected in the serum values of the patients. The most striking finding is the extremely high activity of dipeptidyl peptidase IV in prostatosomes, prostate-derived organelles, which occur freely in human seminal plasma, and which are important for enhancement of sperm forward motility.

Lowered Serum Dipeptidyl Peptidase IV Activity is Associated with Depressive Symptoms and Cytokine Production in Cancer Patients Receiving Interleukin-2-Based Immunotherapy

“…The results that the changes in serum DPP IV are inversely correlated to serum IL-6 and IL-2R suggest that serum DPP IV activity is sensitive to graded differences in IRS activation. These findings are in accordance with previous studies showing that lower serum DPP IV activity accompanies inflammatory disorders, such as rheumatoid arthritis, colitis ulcerosa, autoimmune chronic hepatitis, and systemic lupus erythematosus (Fujita et al 1978;De Meester 1992;De Meester et al 1993).…”

“…Conditions accompanied by activation of the IRS, such as inflammatory and autoimmune disorders (rheumatoid arthritis, autoimmune chronic hepatitis, and systemic lupus erythematosus (Fujita et al 1978;De Meester 1992;De Meester et al 1993) and major depression (Maes et al 1991;Elgun et al 1999) are characterized by lowered serum activity of dipeptidyl peptidase IV (DPP IV; EC 3.4.14.5). The ectoenzyme DPP IV is a membrane-bound serine protease that catalyses the cleavage of dipeptides from the amino-terminus of oligo-and polypeptides under definite structural conditions (De Meester 1992;De Meester et al 1999;HopsuHavu and Glenner 1966;Van Hoof et al 1992).…”

“…The ectoenzyme DPP IV is a membrane-bound serine protease that catalyses the cleavage of dipeptides from the amino-terminus of oligo-and polypeptides under definite structural conditions (De Meester 1992;De Meester et al 1999;HopsuHavu and Glenner 1966;Van Hoof et al 1992). Cytokines, such as tumor necrosis factor-alpha (TNF ␣ ) and transforming growth-factor-␤ (TGF-␤ ) may inhibit DPP IV mRNA expression in renal tubular epithelial and carcinoma cells or the expression of DPP IV enzyme activity (Kehlen et al 1998;Riemann et al 1995).…”

Characterization of a Dipeptidyl Peptidase and its Role in Motility of Rat Epididymal Maturing Spermatozoa

“…We also observed that sitagliptin, a specific inhibitor of DPPIV, has a significant effect on the forward motility of mature caudal spermatozoa. As indicated in previous studies, 45,46 this result indicates the involvement of this peptidase in controlling sperm movement, but the mechanism is still unknown. Although secretion of epididymal fluid is important for the survival and maturation of spermatozoa, the actual role of the proteins in the fluid is yet to be determined.…”

The Janus-faced nature of prostasomes: their pluripotency favours the normal reproductive process and malignant prostate growth

“…91 As mentioned above, DPP IV is derived (among genital glands) nearly exclusively from the prostate gland and more precisely concentrated to an extremely high level in the membrane fraction of prostatic fluid, that is, the prostasomes. 16,17,92 DPP IV hydrolyses biologically active peptides, for example, substance P. 93 Substance P is among the various neuropeptides present Janus-faced nature of prostasomes G Ronquist and BO Nilsson in the prostate gland 94 (although there is so far no report on its occurrence in prostasomes) and it has been found occasionally elevated in plasma in connection with prostate cancer. 95 Hence, DPP IV seems to be involved in activation or deactivation of a broad range of biologically relevant peptides like also growth factors and cytokines.…”