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

Journal Article · Fri Apr 14 04:00:00 EDT 2006 · Biochemical and Biophysical Research Communications

DOI:https://doi.org/10.1016/j.bbrc.2006.02.019· OSTI ID:20798889

Kanasaki, Keizo ^[1]; Haneda, Masakazu ^[2]; Sugimoto, Toshiro ^[1]; Shibuya, Kazuyuki ^[1]; Isono, Motohide ^[1]; Isshiki, Keiji ^[1]; Araki, Shin-ichi ^[1]; Uzu, Takashi ^[1]; Kashiwagi, Atsunori ^[1]; Koya, Daisuke ^[3]

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1. Department of Medicine, Shiga University of Medical Science, Otsu, Shiga (Japan)
2. Second Department of Medicine, Asahikawa Medical College, Asahikawa, Hokkaido (Japan)
3. Division of Endocrinology and Metabolism, Kanazawa Medical University, Ishikawa (Japan)

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.

• OSTI ID: 20798889
• Journal Information: Biochemical and Biophysical Research Communications, Journal Name: Biochemical and Biophysical Research Communications Journal Issue: 3 Vol. 342; ISSN 0006-291X; ISSN BBRCA9
• Country of Publication: United States
• Language: English

Related Subjects

60 APPLIED LIFE SCIENCES
CALVES
CELL CYCLE
CELL PROLIFERATION
DISEASES
DNA
GROWTH FACTORS
INHIBITION
PROLINE
RNA
STEM CELLS
SYNTHESIS
TOXICITY