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Proliferation and Differentiation of Murine Myeloid Precursor 32D/G-CSF-R Cells
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Early growth-responsive-1-dependent manganese superoxide dismutase gene transcription mediated by platelet-derived

K Maehara1, K Oh-Hashi, K I Isobe

  • 1Department of Basic Gerontology, National Institute for Longevity Sciences, 36-3 Gengo, Morioka-cho, Obu, Aichi 474-8522, Japan.

FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology
|August 21, 2001
PubMed

Insights

Platelet-derived growth factor (PDGF) promotes cell survival by upregulating manganese superoxide dismutase (Mn-SOD) gene expression. This process involves the transcription factor Egr-1 and the MEK/ERK signaling pathway, highlighting Mn-SOD

Area of Science:

  • Cell biology
  • Molecular biology
  • Biochemistry

Background:

  • Manganese superoxide dismutase (Mn-SOD) is crucial for mitochondrial protection against oxidative stress and promotes cell survival.
  • Platelet-derived growth factor (PDGF) acts as a survival factor, inhibiting apoptosis and promoting proliferation via signaling pathways.

Purpose of the Study:

  • To investigate the role of PDGF in Mn-SOD gene expression and its underlying molecular mechanisms.
  • To elucidate the involvement of transcription factors and signaling pathways in PDGF-mediated Mn-SOD induction.

Main Methods:

  • NIH3T3 cells were used to study PDGF-induced Mn-SOD expression.
  • Electrophoretic mobility shift assays (EMSA) were performed to assess Egr-1 binding to the Mn-SOD promoter.
  • Transfection studies were conducted to evaluate promoter activity.
  • Western blotting and MEK1 inhibition (U0126) were used to analyze signaling pathways.

Main Results:

  • PDGF significantly induced Mn-SOD gene expression in NIH3T3 cells.
  • PDGF-induced Mn-SOD expression was associated with the transcription factor early growth response-1 (Egr-1).
  • Egr-1 directly bound to the Mn-SOD gene promoter in response to PDGF.
  • The MEK1/ERK1/2 signaling pathway mediated PDGF's induction of Egr-1.

Conclusions:

  • PDGF induces Mn-SOD expression through Egr-1 activation, which binds to the Mn-SOD promoter.
  • The MEK1/ERK1/2 pathway is essential for PDGF-induced Egr-1 and subsequent Mn-SOD upregulation.
  • Mn-SOD induction is a key component of PDGF's anti-apoptotic effects.

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