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Title: N-Acetyl-seryl-aspartyl-lysyl-proline inhibits DNA synthesis in human mesangial cells via up-regulation of cell cycle modulators

Abstract

N-Acetyl-seryl-aspartyl-lysyl-proline (Ac-SDKP) was originally reported as a natural inhibitor of the proliferation of stem cells. To elucidate whether Ac-SDKP inhibits the proliferation of human mesangial cells, we examined the effect of Ac-SDKP on fetal calf serum (FCS)- or platelet-derived growth factor (PDGF)-BB-induced DNA synthesis and a cell proliferation. Ac-SDKP inhibited PDGF-BB- or FCS-induced DNA synthesis without cellular toxicity. The protein expression of p53 and p27{sup kip1} was significantly increased by Ac-SDKP. Ac-SDKP also up-regulated the PDGF-BB-stimulated expression of p21{sup cip1} and suppressed PDGF-BB-induced cyclin D{sub 1} expression. In p53 knock-out human mesangial cells made with small interference RNA, the protein expression of p21{sup cip1} and p27{sup kip1} was also decreased and the inhibitory effect of Ac-SDKP on mesangial proliferation was completely abolished. Ac-SDKP increased the stability of p53 protein as demonstrated by pulse-chase experiment. These results suggest that p53 is the key mediator of Ac-SDKP-induced inhibition of DNA synthesis through the up-regulation of cell cycle modulators, highlighting a potential effect of Ac-SDKP on various progressive renal diseases.

Authors:
 [1];  [2];  [3];  [1];  [1];  [1];  [1];  [1];  [1];  [4]
  1. Department of Medicine, Shiga University of Medical Science, Otsu, Shiga (Japan)
  2. Second Department of Medicine, Asahikawa Medical College, Asahikawa, Hokkaido (Japan)
  3. Department of Medicine, Shiga University of Medical Science, Otsu, Shiga (Japan). E-mail: toshiro@belle.shiga-med.ac.jp
  4. Division of Endocrinology and Metabolism, Kanazawa Medical University, Ishikawa (Japan)
Publication Date:
OSTI Identifier:
20798889
Resource Type:
Journal Article
Resource Relation:
Journal Name: Biochemical and Biophysical Research Communications; Journal Volume: 342; Journal Issue: 3; Other Information: DOI: 10.1016/j.bbrc.2006.02.019; PII: S0006-291X(06)00301-9; Copyright (c) 2006 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; CALVES; CELL CYCLE; CELL PROLIFERATION; DISEASES; DNA; GROWTH FACTORS; INHIBITION; PROLINE; RNA; STEM CELLS; SYNTHESIS; TOXICITY

Citation Formats

Kanasaki, Keizo, Haneda, Masakazu, Sugimoto, Toshiro, Shibuya, Kazuyuki, Isono, Motohide, Isshiki, Keiji, Araki, Shin-ichi, Uzu, Takashi, Kashiwagi, Atsunori, and Koya, Daisuke. N-Acetyl-seryl-aspartyl-lysyl-proline inhibits DNA synthesis in human mesangial cells via up-regulation of cell cycle modulators. United States: N. p., 2006. Web. doi:10.1016/j.bbrc.2006.02.019.
Kanasaki, Keizo, Haneda, Masakazu, Sugimoto, Toshiro, Shibuya, Kazuyuki, Isono, Motohide, Isshiki, Keiji, Araki, Shin-ichi, Uzu, Takashi, Kashiwagi, Atsunori, & Koya, Daisuke. N-Acetyl-seryl-aspartyl-lysyl-proline inhibits DNA synthesis in human mesangial cells via up-regulation of cell cycle modulators. United States. doi:10.1016/j.bbrc.2006.02.019.
Kanasaki, Keizo, Haneda, Masakazu, Sugimoto, Toshiro, Shibuya, Kazuyuki, Isono, Motohide, Isshiki, Keiji, Araki, Shin-ichi, Uzu, Takashi, Kashiwagi, Atsunori, and Koya, Daisuke. Fri . "N-Acetyl-seryl-aspartyl-lysyl-proline inhibits DNA synthesis in human mesangial cells via up-regulation of cell cycle modulators". United States. doi:10.1016/j.bbrc.2006.02.019.
@article{osti_20798889,
title = {N-Acetyl-seryl-aspartyl-lysyl-proline inhibits DNA synthesis in human mesangial cells via up-regulation of cell cycle modulators},
author = {Kanasaki, Keizo and Haneda, Masakazu and Sugimoto, Toshiro and Shibuya, Kazuyuki and Isono, Motohide and Isshiki, Keiji and Araki, Shin-ichi and Uzu, Takashi and Kashiwagi, Atsunori and Koya, Daisuke},
abstractNote = {N-Acetyl-seryl-aspartyl-lysyl-proline (Ac-SDKP) was originally reported as a natural inhibitor of the proliferation of stem cells. To elucidate whether Ac-SDKP inhibits the proliferation of human mesangial cells, we examined the effect of Ac-SDKP on fetal calf serum (FCS)- or platelet-derived growth factor (PDGF)-BB-induced DNA synthesis and a cell proliferation. Ac-SDKP inhibited PDGF-BB- or FCS-induced DNA synthesis without cellular toxicity. The protein expression of p53 and p27{sup kip1} was significantly increased by Ac-SDKP. Ac-SDKP also up-regulated the PDGF-BB-stimulated expression of p21{sup cip1} and suppressed PDGF-BB-induced cyclin D{sub 1} expression. In p53 knock-out human mesangial cells made with small interference RNA, the protein expression of p21{sup cip1} and p27{sup kip1} was also decreased and the inhibitory effect of Ac-SDKP on mesangial proliferation was completely abolished. Ac-SDKP increased the stability of p53 protein as demonstrated by pulse-chase experiment. These results suggest that p53 is the key mediator of Ac-SDKP-induced inhibition of DNA synthesis through the up-regulation of cell cycle modulators, highlighting a potential effect of Ac-SDKP on various progressive renal diseases.},
doi = {10.1016/j.bbrc.2006.02.019},
journal = {Biochemical and Biophysical Research Communications},
number = 3,
volume = 342,
place = {United States},
year = {Fri Apr 14 00:00:00 EDT 2006},
month = {Fri Apr 14 00:00:00 EDT 2006}
}