Inhibition and stimulation of growth of Entamoeba histolytica in culture: Association with PKC activity and protein phosphorylation

We studied the role of protein kinase C (PKC) and protein threonine phospho rylation in the inhibition and stimulation of growth of the protozoan paras ite Entamoeba histolytica. PKC was activated after serum deprivation in E. histolytica and during this period proteins became threonine phosphorylated . Conversely, on serum stimulation of serum-deprived cells, PKC activation was rapidly reversed and the threonine phosphorylation of proteins quickly declined. Growth of E. histolytica was not affected by either PKC inhibitor s H-7 and GF109203X or by down-regulation of PKC by Phorbol 12-Myristate 13 -Acetate (PMA). Interestingly, very low doses of PMA which caused activatio n of PKC and were unable to down-regulate PKC after 48 h of culture, negati vely influenced the growth of E. histolytica. Serine/threonine phosphatase inhibitors Okadaic acid and Calyculin A drastically inhibited growth of E. histolytica. In conclusion, the growth of E. histolytica is not adversely a ffected by PKC down-regulation. On the contrary, growth inhibition of E. hi stolytica is associated with activation of Ca2+, Diacylglyceol (DAG)-depend ent PKC, and threonine phosphorylation of proteins. (C) 2000 Academic Press .