Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C1519176 (PSA)
 5,490 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

IGFBPs play an important role in IGF biological actions by modulating IGF binding to its receptors. The major IGFBP in serum is IGFBP-3, which transports 70-90% of the circulating IGFs. In target cell systems, it sequesters IGFs and inhibits their hormonal actions, but may potentiate IGF activity or exert IGF-independent effects under specific conditions. IGFBP-3 can be modified by IGFBP-3 proteases, which degrade it into smaller fragments. IGFBP-3 fragments generated by proteolysis have reduced affinity for IGFs, thereby modifying IGF action. To study IGFBP-3 fragments in vivo and in vitro, we constructed six different IGFBP-3 fragments by use of a baculovirus expression system and generated 8 different monoclonal IGFBP-3 antibodies. Based on the known cleavage sites of IGFBP-3 for PSA, MMPs, and the predicted plasmin cleavage sites, we expressed a N-terminal IGFBP-3(1-97) fragment and a C-terminal IGFBP-3(98-264) fragment. By stepwise truncation from the C-terminal end, we created IGFBP-3(98-232), IGFBP-3(98-206), IGFBP-3(98-179), and IGFBP-3(98-159). A strong recognition of the C-terminus and the intermediate parts of IGFBP-3 by six antibodies was found. Four of these mAbs were able to recognize the intermediate fragment alone. Two mAbs were found to immunoreact only with the N-terminal IGFBP-3 fragment and two additional mAbs recognized the N- as well as the C-terminal parts and lacked immunoreactivity for the intermediate part of IGFBP-3. The 15 kDa IGFBP-3 fragment resulting from plasmin digestion was found to only react with N-terminal antibodies, while the 29 kDa fragment in pregnancy serum reacted with both N- and C-terminal antibodies. Thus, these mAbs will be useful tools to determine whether IGFBP-3 fragments found in vivo derive from either the N- or C-terminal domains of IGFBP-3.
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PMID:Synthesis of IGFBP-3 fragments in a baculovirus system and characterization of monoclonal anti-IGFBP-3 antibodies. 921 21

Benign prostatic hyperplasia (BPH) represents a pattern of non-malignant growth of prostatic fibromuscular stroma. Metabolic disturbances such us pre-diabetes and metabolic syndrome may have a role in BPH pathophysiology. A potential explanation for the above relationship involves the insulin-like growth factor (IGF) axis as well as IGF binding proteins, (IGFBPs) of which the most abundant form is IGFBP-3. Therefore, the aim of the present study was to investigate the association between intra-prostatic levels of IGF-1, IGF-2 as well as to evaluate the role of locally expressed IGFBP-3 in BPH development in pre-diabetes. A total of 49 patients admitted to the Urology department of a tertiary urban Greek hospital, for transurethral prostate resection, or prostatectomy and with pre-diabetes [impaired fasting glucose (IFG) and impaired glucose tolerance (IGT) or both] were finally included. The majority of the sample consisted of subjects with IGT (51.0%), followed by IFG and IGT (32.7%) and isolated IFG (16.3%). For all participants a clinical examination was performed and blood samples were collected. In addition, total prostate (TP) volume or transitional zone (TZ) volume were estimated by transrectal ultrasonography. The results of the multivariate analysis regarding TP volume showed that higher PSA (p<0.001), larger waist circumference (p=0.007) and higher IGFBP-3 expression levels (p<0.001) independently predicted higher TP volume. The results regarding the volume of the TZ showed that higher PSA (p<0.001), larger waist circumference (p<0.001) and higher IGFBP-3 expression levels (p=0.024) were independently associated with higher TZ volume. Our findings show that intra-prostatic levels of IGFBP-3, PSA and waist circumference, but not overall obesity, are positively associated with prostate volume. IGFBP-3 seems to be a multifunctional protein, which can potentiate or inhibit IGF activity.
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PMID:Linking pre-diabetes with benign prostate hyperplasia. IGFBP-3: a conductor of benign prostate hyperplasia development orchestra? 2436 83