Epidermal growth factor inhibits Na-Pi cotransport and mRNA in OK cells

Mazen Arar, Michel Baum, Jurg Biber, Heini Murer, Moshe Levi

Research output: Contribution to journalArticle

37 Citations (Scopus)

Abstract

The present study examined the effect of epidermal growth factor (EGF) on Na-Pi cotransport in a tubular epithelial cell line derived from the opossum kidney (OKP cells). EGF caused a time- and dose-dependent decrease in Na-Pi cotransport. The inhibition of Na-Pi cotransport by 10-8 M EGF was first demonstrable after 18 h with maximal effect seen at 24 h. EGF inhibited Na-Pi cotransport by decreasing the maximal velocity (10.8 ± 0.9 in control vs. 4.9 ± 0.8 nmol 32Pi·4 min-1·mg protein-1 in EGF, P < 0.001). Northern blot analysis indicated that EGF caused a significant decrease in NaPi-4 mRNA abundance. The abundance of NaPi-4 mRNA relative to β-actin and/or glyceraldehyde-3-phosphate dehydrogenase mRNA was decreased by twofold in OK cells treated with EGF for 4 h and threefold in OKP cells treated with EGF for 24 h. Thus the decrease in NaPi-4 mRNA abundance preceded the decrease in Na-Pi cotransport activity. Inhibition of transcription with actinomycin D and protein synthesis with cycloheximide prevented the inhibition of Na-Pi cotransport. Furthermore, inhibition of phospholipase C activity with U-73,122 also significantly blocked the inhibitory effect of EGF on Na-Pi cotransport. The results indicate that EGF-induced decrease in OKP Na-Pi cotransport is mediated through a decrease in NaPi-4 mRNA and activation of the phospholipase C signaling pathway.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Renal Fluid and Electrolyte Physiology
Volume268
Issue number2 37-2
StatePublished - Feb 1995

Fingerprint

epidermal growth factor
Epidermal Growth Factor
Messenger RNA
cells
phospholipase C
Type C Phospholipases
Opossums
Glyceraldehyde-3-Phosphate Dehydrogenases
actinomycin D
glyceraldehyde-3-phosphate dehydrogenase
Dactinomycin
opossums
cycloheximide
Cycloheximide
kidney cells
Northern blotting
Northern Blotting
actin
Actins
Proteins

Keywords

  • Phospholipase C
  • Sodium phosphate 4 messenger ribonucleic acid
  • Transcription
  • Translation

ASJC Scopus subject areas

  • Physiology
  • Agricultural and Biological Sciences(all)

Cite this

Epidermal growth factor inhibits Na-Pi cotransport and mRNA in OK cells. / Arar, Mazen; Baum, Michel; Biber, Jurg; Murer, Heini; Levi, Moshe.

In: American Journal of Physiology - Renal Fluid and Electrolyte Physiology, Vol. 268, No. 2 37-2, 02.1995.

Research output: Contribution to journalArticle

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abstract = "The present study examined the effect of epidermal growth factor (EGF) on Na-Pi cotransport in a tubular epithelial cell line derived from the opossum kidney (OKP cells). EGF caused a time- and dose-dependent decrease in Na-Pi cotransport. The inhibition of Na-Pi cotransport by 10-8 M EGF was first demonstrable after 18 h with maximal effect seen at 24 h. EGF inhibited Na-Pi cotransport by decreasing the maximal velocity (10.8 ± 0.9 in control vs. 4.9 ± 0.8 nmol 32Pi·4 min-1·mg protein-1 in EGF, P < 0.001). Northern blot analysis indicated that EGF caused a significant decrease in NaPi-4 mRNA abundance. The abundance of NaPi-4 mRNA relative to β-actin and/or glyceraldehyde-3-phosphate dehydrogenase mRNA was decreased by twofold in OK cells treated with EGF for 4 h and threefold in OKP cells treated with EGF for 24 h. Thus the decrease in NaPi-4 mRNA abundance preceded the decrease in Na-Pi cotransport activity. Inhibition of transcription with actinomycin D and protein synthesis with cycloheximide prevented the inhibition of Na-Pi cotransport. Furthermore, inhibition of phospholipase C activity with U-73,122 also significantly blocked the inhibitory effect of EGF on Na-Pi cotransport. The results indicate that EGF-induced decrease in OKP Na-Pi cotransport is mediated through a decrease in NaPi-4 mRNA and activation of the phospholipase C signaling pathway.",
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