Tumor promoter 12‐0‐tetradecanoyl‐phorbol‐13‐acetate (TPA) can reduce the Ca‐transporting ability of Ca‐lonophores in T lymphocytes: The involvement of intracellular heavy metal lons

Péter Csermely, János Somogyi

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

12‐0‐tetradecanoyl‐phorbol‐13‐acetate (TPA) can significantly reduce the Caionophore‐induced rise in the intracellular calcium concentration (Cai) of T lymphocytes measured by quin2 or fura‐2 fluorescence. This counteraction of TPA is maximal at a preincubation of 90 min at TPA concentrations higher than 20 nM. 45Ca uptake and efflux measurements directly indicate that TPA does not activate the calcium extrusion systems in thymocytes but impairs the Ca‐transporting ability of Ca‐ionophores. TPA causes no immobilization of the Ca‐ionophores as it is demonstrated by the lack of significant changes in fluorescence and fluorescence polarisation of A23187 during TPA incubation. Similarly the energy transfer between the Tyr, Try groups of membrane proteins and A23187 shows no significant difference in control and TPA treated thymocytes. This indicates that A23187 is not in a membrane proteinbound form after TPA preincubation. The intracellular heavy metal chelator, N,N,N′,N′‐tetrakis(2‐pyridylmethyl)ethylenediamine (TPEN) restores the ionophoretic ability of Ca‐ionophores in TPA pretreated cells to the control level. Diacyl‐glycerols also impair the Ca‐transporting ability of Ca‐ionophores. TPEN prevents this effect as well. These findings suggest that TPA and diacylglycerols may cause an increase in the availability of intracellular heavy metal ions. Our results may reflect a new, physiologically important mechanism of the action of diacyl‐glycerols and phorbol esters.

Original languageEnglish
Pages (from-to)593-602
Number of pages10
JournalJournal of Cellular Physiology
Volume138
Issue number3
DOIs
Publication statusPublished - Mar 1989

ASJC Scopus subject areas

  • Physiology
  • Clinical Biochemistry
  • Cell Biology

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