PMID- 20868675
OWN - NLM
STAT- MEDLINE
DCOM- 20110303
LR  - 20220408
IS  - 1879-0712 (Electronic)
IS  - 0014-2999 (Linking)
VI  - 649
IP  - 1-3
DP  - 2010 Dec 15
TI  - Prolidase-dependent regulation of TGF beta (corrected) and TGF beta receptor 
      expressions in human skin fibroblasts.
PG  - 115-9
LID - 10.1016/j.ejphar.2010.09.034 [doi]
AB  - Transforming growth factor beta 1 (TGF beta1) is a protein that in most cells 
      control proliferation and differentiation. One of the best characterized 
      functions of TGF beta1 is stimulation of collagen biosynthesis that may lead to 
      tissue fibrosis. Several reports suggest that prolidase, through regulation of 
      expression of growth factors and transcription factors, e.g. vascular endothelial 
      growth factor (VEGF) and hypoxia-inducible factor-1alpha (HIF-1 alpha) may be important 
      in many physiologic and pathophysiologic processes like: wound healing, 
      inflammation and angiogenesis. We found that inhibitors of prolidase activity 
      (N-benzyloxycarbonyl-l-proline, Cbz-Pro and phosphoenolopyruvate, PEP) induced 
      decrease in TGF beta1 and its receptor expressions. On the other hand, products of 
      prolidase catalytic activity, proline (Pro) and hydroxyproline (HyPro) induced 
      increase in the amount of TGF beta1 and TGF beta receptors. Simultaneously, inhibitors 
      of prolidase induced down-regulation of expression of the phospho-AKT. An 
      addition of Pro or HyPro to the cells induced increase in the expression of 
      phospho-AKT. An important transcription factor involved in signal induced by TGF 
      beta receptor is mammalian target of rapamycin (mTOR). We found that prolidase 
      inhibitors induced decrease in the expression of phospho-mTOR, while Pro or HyPro 
      counteracted the effect. Rapamycin (pharmacological inhibitor of mTOR) resulted 
      in decrease in prolidase activity. The down-regulation of phospho-mTOR by 
      rapamycin contributed to down-regulation of prolidase activity suggesting its 
      important role in prolidase-dependent function. It seems, that products of 
      prolidase activity, Pro or HyPro may act as an interface between mTOR and 
      phospho-mTOR in regulation of numerous TGF beta receptor-dependent functions.
CI  - Copyright (c) 2010 Elsevier B.V. All rights reserved.
FAU - Surazynski, Arkadiusz
AU  - Surazynski A
AD  - Department of Medicinal Chemistry, Medical University in Bialystok, Kilinskiego 
      1, 15-230 Bialystok, Poland.
FAU - Miltyk, Wojciech
AU  - Miltyk W
FAU - Prokop, Izabela
AU  - Prokop I
FAU - Palka, Jerzy
AU  - Palka J
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20100921
PL  - Netherlands
TA  - Eur J Pharmacol
JT  - European journal of pharmacology
JID - 1254354
RN  - 0 (Protease Inhibitors)
RN  - 0 (Protein Kinase Inhibitors)
RN  - 0 (Receptors, Transforming Growth Factor beta)
RN  - 0 (TGFB1 protein, human)
RN  - 0 (Transforming Growth Factor beta1)
RN  - 1148-11-4 (carbobenzoxyproline)
RN  - 73-89-2 (Phosphoenolpyruvate)
RN  - 9DLQ4CIU6V (Proline)
RN  - EC 2.7.1.1 (MTOR protein, human)
RN  - EC 2.7.11.1 (Protein Serine-Threonine Kinases)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - EC 2.7.11.30 (Receptor, Transforming Growth Factor-beta Type I)
RN  - EC 3.4.13.- (Dipeptidases)
RN  - EC 3.4.13.9 (proline dipeptidase)
RN  - RMB44WO89X (Hydroxyproline)
RN  - W36ZG6FT64 (Sirolimus)
SB  - IM
MH  - Cells, Cultured
MH  - Dipeptidases/antagonists & inhibitors/*physiology
MH  - Down-Regulation/*drug effects
MH  - Fibroblasts/drug effects/metabolism
MH  - Humans
MH  - Hydroxyproline/metabolism
MH  - Osmolar Concentration
MH  - Phosphoenolpyruvate/metabolism
MH  - Phosphorylation/drug effects
MH  - Proline/analogs & derivatives/metabolism/pharmacology
MH  - Protease Inhibitors/pharmacology
MH  - Protein Kinase Inhibitors/pharmacology
MH  - Protein Serine-Threonine Kinases/*metabolism
MH  - Proto-Oncogene Proteins c-akt/metabolism
MH  - Receptor, Transforming Growth Factor-beta Type I
MH  - Receptors, Transforming Growth Factor beta/*metabolism
MH  - Sirolimus/pharmacology
MH  - Skin/drug effects/*metabolism
MH  - TOR Serine-Threonine Kinases/antagonists & inhibitors/metabolism
MH  - Transforming Growth Factor beta1/metabolism
MH  - Up-Regulation
EDAT- 2010/09/28 06:00
MHDA- 2011/03/04 06:00
CRDT- 2010/09/28 06:00
PHST- 2010/04/23 00:00 [received]
PHST- 2010/07/15 00:00 [revised]
PHST- 2010/09/14 00:00 [accepted]
PHST- 2010/09/28 06:00 [entrez]
PHST- 2010/09/28 06:00 [pubmed]
PHST- 2011/03/04 06:00 [medline]
AID - S0014-2999(10)00919-2 [pii]
AID - 10.1016/j.ejphar.2010.09.034 [doi]
PST - ppublish
SO  - Eur J Pharmacol. 2010 Dec 15;649(1-3):115-9. doi: 10.1016/j.ejphar.2010.09.034. 
      Epub 2010 Sep 21.