当前位置： SCI文献检索 > JOURNAL OF CELLULAR PHYSIOLOGY期刊下所有文献 > Transition metal chelator TPEN counteracts phorbol ester-induced actin cytoskeletal disruption in C6 rat glioma cells without inhibiting activation or translocation of protein kinase C.

Transition metal chelator TPEN counteracts phorbol ester-induced actin cytoskeletal disruption in C6 rat glioma cells without inhibiting activation or translocation of protein kinase C.

Abstract：

:Phorbol ester-induced reorganization of the actin cytoskeleton was investigated in C6 rat glioma cells. Observations by fluorescence microscopy and photoelectron microscopy indicated that pretreatment with the transition metal chelator N,N,N',N'-tetrakis(2-pyridylmethyl)ethylenediamine (TPEN) for 1-2 h at 50 microM reduced the sensitivity of the actin cytoskeleton to disruption by the subsequent addition of 200 nM phorbol myristate acetate (PMA). The protective effect of TPEN was eliminated by adding back Zn2+ prior to PMA addition, implicating chelation of metal ions as the mechanism of action of TPEN. C6 cells exposed to PMA experience potent activation of protein kinase C (PKC) and substantial redistribution of the kinase from a soluble to a particulate cellular fraction (translocation). TPEN pretreatment did not block PKC translocation in PMA-exposed cells. By two-dimensional gel analysis, TPEN also did not reduce, but rather slightly increased, the PMA-stimulated phosphorylation of the acidic 80 kDa endogenous PKC substrate, as well as two other proteins at 18 kDa and 50 kDa. In contrast, TPEN significantly suppressed phosphorylation of a 20 kDa protein, both in cells treated with TPEN only and in TPEN-pretreated PMA-exposed cells. The results indicate that the ability of TPEN to protect against PKC-mediated actin cytoskeletal disruption is not due to either a block of PKC translocation or to general inhibition of PKC activity. Rather, the action of TPEN is more selective and probably involves chelation of Zn2+ at a critical Zn(2+)-dependent phosphorylation step downstream from the initial tumor promoter-induced effects on PKC.

journal_name

J Cell Physiol

journal_title

Journal of cellular physiology

authors

Hedberg KK,Birrell GB,Mobley PL,Griffith OH

doi

10.1002/jcp.1041580216

subject

Has Abstract

pub_date

1994-02-01 00:00:00

pages

337-46

issue

eissn

0021-9541

issn

1097-4652

journal_volume

158

pub_type

杂志文章

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Transition metal chelator TPEN counteracts phorbol ester-induced actin cytoskeletal disruption in C6 rat glioma cells without inhibiting activation or translocation of protein kinase C.