Regulation of cadmium-induced apoptosis by PKCdelta in U937 human promonocytic cells.
Pulse treatment with cadmium chloride followed by recovery caused apoptosis in U937 human promonocytic cells. In addition, the treatment-induced PKCdelta translocation from cytosol to membrane fraction, which was already detected at 30 min of treatment; and also caused PKCdelta cleavage to give a 41-kDa fragment, which was detected at 3-6 h of recovery, concomitantly with the execution of apoptosis. All these effects were reduced by the PKCdelta-specific inhibitor rottlerin. By contrast, rottlerin did not prevent the cadmium-provoked stimulation of the stress response (as measured by HSP70 expression), nor inhibited the generation of apoptosis by heat-shock, which failed to cause PKCdelta translocation. Cadmium chloride rapidly induced p38(MAPK) activation, which was not affected by rottlerin. By contrast, the p38(MAPK) inhibitor SB203580 reduced PKCdelta translocation and cleavage, indicating that p38(MAPK) activation precedes and regulates PKCdelta activation. It is concluded that PKCdelta mediates apoptosis induction by cadmium ions via early membrane translocation, and also possibly through late kinase proteolytic cleavage and phosphorylation on tyrosine residues.
Miguel
Begoña G
BG
Dept. Bioquímica y Biología Molecular I, Facultad de Biología, Universidad Complutense de Madrid, 28040 Madrid, Spain.
Rodriguez
M Elena
ME
Aller
Patricio
P
Martinez
Ana M
AM
Mata
Felicísima
F
D000098:Acetophenones / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D001578:Benzopyrans / Q000494:pharmacology; D002104:Cadmium / Q000494:pharmacology*; D019256:Cadmium Chloride / Q000494:pharmacology; D004789:Enzyme Activation / Q000187:drug effects; D006801:Humans; D007527:Isoenzymes / Q000502:physiology; D010766:Phosphorylation; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000502:physiology*; D020298:U937 Cells; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
D000098:Acetophenones; D001578:Benzopyrans; D007527:Isoenzymes; D002104:Cadmium; C085746:rottlerin; D011493:Protein Kinase C; D048051:p38 Mitogen-Activated Protein Kinases; D019256:Cadmium Chloride