US EPA

1489283 

Journal Article 

COPPER DEFICIENCY ALTERS PROTEIN-KINASE-C MEDIATION OF THROMBIN-INDUCED DENSE GRANULE SECRETION FROM RAT PLATELETS 

Johnson, WT; Dufault, SN 

1991 

1 

Journal of Nutritional Biochemistry
ISSN: 0955-2863
EISSN: 1873-4847 

2 

12 

663-670 

English 

10113/48346 

WOS:A1991GT06300005 

http://://WOS:A1991GT06300005
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Experiments were conducted to determine if copper
deficiency enhances the rate of thrombin-induced dense granule secretion by modifying the major
signal transduction pathways of rat platelets. Platelets were obtained from male, weanling
Sprague-Dawley rats fed diets containing either deficient (< 0.5-mu-g/g diet) or adequate (5.5-
mu-g/g diet) copper for 5 weeks. Following stimulation with thrombin (0.1 U/mL), the rate of
dense granule secretion as measured by ATP release was 160% higher in platelets from copper-
deficient than from control rats. Inhibition of the rate of thrombin-induced ATP release by (6-
aminohexyl)-1-naphthalene-sulfonamide, a calmodulin antagonist was independent of copper status.
However, 1-(5-isoquinoline-sulfonyl)-2-methylpiperazine, a protein kinase C inhibitor, inhibited
the rate of ATP release only in platelets from copper-deficient rats. Aspirin had no effect on
ATP release from platelets obtained from either copper-deficient or control rats. This suggests
that copper deficiency alters the role of protein kinase C in regulating dense granule secretion.
Analysis of autoradiographs showing [P-32]-labeled platelet proteins indicated that the
phosphorylation of a 40 kDa protein, a known substrate for protein kinase C in platelets, was
significantly less following thrombin stimulation in platelets from copper-deficient than from
control rats. When protein kinase C was activated by phorbol 12-myristate 13-acetate prior to
thrombin stimulation, ATP release was attenuated regardless of copper status. These findings
suggest that protein kinase C can still function as a feedback inhibitor of platelet dense
granule secretion in copper deficiency, but impaired activation of this enzyme following thrombin
stimulation may prevent it from achieving full regulatory capacity. 

COPPER DEFICIENCY; PLATELETS; SECRETION; PROTEIN KINASE-C