Effect of Endothelin-1 (1-31) on Human Mesangial Cell Proliferation

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Author(s)

Abstract

It was previously found that human chymase cleaves big endothelins(ETs)at the Tyr<SUP>3</SUP>1−Gly<SUP>3</SUP>2 bond and produces 31−amino acid ETs(1−31).In the present study, human plasma concentrations of ET−1(1−31)and ET−1 were examined and the effect of synthetic ET−1(1−31)on the proliferation of cultured human mesangial cells(HMCs)was investigated.The proliferative effect of ET−1(1−31)was evaluated from the [<SUP>3</SUP>H]−thymidine uptake.The activity of extracellular signal−regulated kinase(ERK)and DNA binding activity of activator protein−1 were determined by using an in−gel kinase assay and gel mobility shift assay, respectively.Immunoreactive ET−1(1−31)was detectable in plasma, but the level was slightly lower than that of ET−1.ET−1(1−31)increased [<SUP>3</SUP>H]−thymidine incorporation in HMCs to a degree similar to that induced by ET−1.ET−1(1−31)also activated ERK1/2.Inhibition of protein kinase C and ERK kinase caused a reduction of ET−1(1−31)−induced ERK1/2 activation.The ERK1/2 activation was followed by an increase in transcription factor activator protein−1 DNA binding activity.These findings suggest that ET−1(1−31)is a bioactive peptide in humans and ET−1(1−31)itself stimulates HMC proliferation.

Journal

  • The Japanese Journal of Pharmacology

    The Japanese Journal of Pharmacology 84(2), 146-155, 2000-10-01

    The Japanese Pharmacological Society

References:  45

Cited by:  1

Codes

  • NII Article ID (NAID)
    10008185571
  • NII NACSIS-CAT ID (NCID)
    AA00691188
  • Text Lang
    ENG
  • Article Type
    Journal Article
  • ISSN
    00215198
  • NDL Article ID
    5549225
  • NDL Source Classification
    ZS51(科学技術--薬学)
  • NDL Call No.
    Z53-D199
  • Data Source
    CJP  CJPref  NDL  J-STAGE 
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