Long-term activation of protein kinase C causes chronic Na/H antiporter stimulation in cultured proximal tubule cells

Shigeo Horie, Orson Moe, R. Tyler Miller, Robert J. Alpern

Research output: Contribution to journalArticle

44 Citations (Scopus)

Abstract

To examine the role of protein kinase C as a chronic regulator of proximal tubule Na/H antiporter activity, the effect of phorbol 12-myristate 13-acetate (PMA) on the Na/H antiporter was studied in cultured proximal tubule cells. Short-term activation of protein kinase C by 5 min exposure to PMA caused an acute increase in Na/H antiporter activity that was not prevented by cycloheximide or actinomycin D and did not persist 24 h later. Long-term activation of protein kinase C by 2 h exposure to PMA caused a dose-dependent increase in Na/H antiporter activity 24 h later. This latter effect was due to protein kinase C activation in that it was inhibited by sphingosine and was not seen with 4α-PMA, an inactive analogue. The chronic effect of PMA was inhibited by 10 nM actinomycin D or 7 μM cycloheximide. Proximal tubule cells exposed to PMA for 2 h demonstrated a two- to threefold increase in Na/H antiporter mRNA (mRNANa/H) abundance 4 h later. In conclusion, short-term activation of protein kinase C leads to a transient increase in Na/H antiporter activity that is independent of transcription and translation, whereas long-term activation of protein kinase C causes a persistent increase in antiporter activity that is dependent on transcription and translation and is associated with increased mRNANa/H abundance. This latter effect may mediate increased Na/H antiporter activity in a number of chronic conditions.

Original languageEnglish (US)
Pages (from-to)365-372
Number of pages8
JournalJournal of Clinical Investigation
Volume89
Issue number2
StatePublished - 1992

Fingerprint

Sodium-Hydrogen Antiporter
Protein Kinase C
Acetates
Dactinomycin
Cycloheximide
Antiporters
Sphingosine
phorbol-12-myristate
Messenger RNA

Keywords

  • Actinomycin D
  • Cycloheximide
  • Memory
  • Northern blot
  • Phorbol esters

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Long-term activation of protein kinase C causes chronic Na/H antiporter stimulation in cultured proximal tubule cells. / Horie, Shigeo; Moe, Orson; Miller, R. Tyler; Alpern, Robert J.

In: Journal of Clinical Investigation, Vol. 89, No. 2, 1992, p. 365-372.

Research output: Contribution to journalArticle

@article{322bf30f0f8242e6a892c59b473e8402,
title = "Long-term activation of protein kinase C causes chronic Na/H antiporter stimulation in cultured proximal tubule cells",
abstract = "To examine the role of protein kinase C as a chronic regulator of proximal tubule Na/H antiporter activity, the effect of phorbol 12-myristate 13-acetate (PMA) on the Na/H antiporter was studied in cultured proximal tubule cells. Short-term activation of protein kinase C by 5 min exposure to PMA caused an acute increase in Na/H antiporter activity that was not prevented by cycloheximide or actinomycin D and did not persist 24 h later. Long-term activation of protein kinase C by 2 h exposure to PMA caused a dose-dependent increase in Na/H antiporter activity 24 h later. This latter effect was due to protein kinase C activation in that it was inhibited by sphingosine and was not seen with 4α-PMA, an inactive analogue. The chronic effect of PMA was inhibited by 10 nM actinomycin D or 7 μM cycloheximide. Proximal tubule cells exposed to PMA for 2 h demonstrated a two- to threefold increase in Na/H antiporter mRNA (mRNANa/H) abundance 4 h later. In conclusion, short-term activation of protein kinase C leads to a transient increase in Na/H antiporter activity that is independent of transcription and translation, whereas long-term activation of protein kinase C causes a persistent increase in antiporter activity that is dependent on transcription and translation and is associated with increased mRNANa/H abundance. This latter effect may mediate increased Na/H antiporter activity in a number of chronic conditions.",
keywords = "Actinomycin D, Cycloheximide, Memory, Northern blot, Phorbol esters",
author = "Shigeo Horie and Orson Moe and Miller, {R. Tyler} and Alpern, {Robert J.}",
year = "1992",
language = "English (US)",
volume = "89",
pages = "365--372",
journal = "Journal of Clinical Investigation",
issn = "0021-9738",
publisher = "The American Society for Clinical Investigation",
number = "2",

}

TY - JOUR

T1 - Long-term activation of protein kinase C causes chronic Na/H antiporter stimulation in cultured proximal tubule cells

AU - Horie, Shigeo

AU - Moe, Orson

AU - Miller, R. Tyler

AU - Alpern, Robert J.

PY - 1992

Y1 - 1992

N2 - To examine the role of protein kinase C as a chronic regulator of proximal tubule Na/H antiporter activity, the effect of phorbol 12-myristate 13-acetate (PMA) on the Na/H antiporter was studied in cultured proximal tubule cells. Short-term activation of protein kinase C by 5 min exposure to PMA caused an acute increase in Na/H antiporter activity that was not prevented by cycloheximide or actinomycin D and did not persist 24 h later. Long-term activation of protein kinase C by 2 h exposure to PMA caused a dose-dependent increase in Na/H antiporter activity 24 h later. This latter effect was due to protein kinase C activation in that it was inhibited by sphingosine and was not seen with 4α-PMA, an inactive analogue. The chronic effect of PMA was inhibited by 10 nM actinomycin D or 7 μM cycloheximide. Proximal tubule cells exposed to PMA for 2 h demonstrated a two- to threefold increase in Na/H antiporter mRNA (mRNANa/H) abundance 4 h later. In conclusion, short-term activation of protein kinase C leads to a transient increase in Na/H antiporter activity that is independent of transcription and translation, whereas long-term activation of protein kinase C causes a persistent increase in antiporter activity that is dependent on transcription and translation and is associated with increased mRNANa/H abundance. This latter effect may mediate increased Na/H antiporter activity in a number of chronic conditions.

AB - To examine the role of protein kinase C as a chronic regulator of proximal tubule Na/H antiporter activity, the effect of phorbol 12-myristate 13-acetate (PMA) on the Na/H antiporter was studied in cultured proximal tubule cells. Short-term activation of protein kinase C by 5 min exposure to PMA caused an acute increase in Na/H antiporter activity that was not prevented by cycloheximide or actinomycin D and did not persist 24 h later. Long-term activation of protein kinase C by 2 h exposure to PMA caused a dose-dependent increase in Na/H antiporter activity 24 h later. This latter effect was due to protein kinase C activation in that it was inhibited by sphingosine and was not seen with 4α-PMA, an inactive analogue. The chronic effect of PMA was inhibited by 10 nM actinomycin D or 7 μM cycloheximide. Proximal tubule cells exposed to PMA for 2 h demonstrated a two- to threefold increase in Na/H antiporter mRNA (mRNANa/H) abundance 4 h later. In conclusion, short-term activation of protein kinase C leads to a transient increase in Na/H antiporter activity that is independent of transcription and translation, whereas long-term activation of protein kinase C causes a persistent increase in antiporter activity that is dependent on transcription and translation and is associated with increased mRNANa/H abundance. This latter effect may mediate increased Na/H antiporter activity in a number of chronic conditions.

KW - Actinomycin D

KW - Cycloheximide

KW - Memory

KW - Northern blot

KW - Phorbol esters

UR - http://www.scopus.com/inward/record.url?scp=0026594771&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0026594771&partnerID=8YFLogxK

M3 - Article

C2 - 1310692

AN - SCOPUS:0026594771

VL - 89

SP - 365

EP - 372

JO - Journal of Clinical Investigation

JF - Journal of Clinical Investigation

SN - 0021-9738

IS - 2

ER -