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Title: Stage-specific cytosolic protein kinase C-like activity in human malarial parasite Plasmodium falciparum
Authors: Sharma, Arun
Biswas, Sukla
Keywords: Malaria
Plasmodium falciparum
Protein kinase C
Drug resistance
Phorbol myristate acetate
Phosphatidyl serine
Issue Date: Jun-2005
Publisher: CSIR
IPC CodeA 61 P 33/06
Abstract: Protein kinase C (PKC)-like activity was characterized in malarial parasite Plasmodium falciparum and its involvement in growth, maturation and differentiation functions, during the asexual stages (ring, trophozoite and schizont) of development was studied. PKC-like activity was found distributed in all the stages of the parasite maturation. The activity was predominantly cytosolic, however it was also present in the membrane fraction. The activation of cytosolic PKC required Ca²⁺, phosphatidyl serine (PS), and either diacylglycerol or phorbol myristate acetate (PMA). The 9-fold increase in the activity was observed in the presence of the co-factors (Ca²⁺, PS and PMA) in the late trophozoite stage, as compared to the ring stage. The activation of trophozoites with PMA resulted in redistribution of PKC-like activity from cytosol to membrane fractions. An antimalarial drug, chloroquine (CQ) inhibited directly the PKC-like activity in a dose-dependent manner (IC₅₀ of 45 nM) in trophozoites of chloroquine-sensitive CQ(S) strains, however, the activity remained unaltered in the chloroquine-resistant CQ(R) strains. Kinetic studies showed that the inhibition of cytosolic PKC-like activity by CQ was non-competitive with respect to ATP, histone and PS. The results suggest that the PKC-like activity is developmentally expressed during the parasitic survival and development.
Page(s): 145-151
ISSN: 0301-1208
Source:IJBB Vol.42(3) [June 2005]

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