Changes in Trypanosoma cruzi infectivity by treatments that affect calcium ion levels.
The possible role of the intracellular Ca2+ level in the regulation of Trypanosoma cruzi infectivity was explored by measuring the capacity of trypomastigote forms of this organism to invade mammalian host cells after treatments which decrease or elevate cytoplasmic Ca2+. Parasites loaded with either bis-(o-aminophenoxy)-ethane-N,N,N',N' tetraacetic acid (BAPTA) or 2-([2-bis(carboxymethyl)-amino-5-methylphenoxy]methyl)-6-nethoxy-8 - bis(carboxymethyl)aminoquinoline (Quin-2) to chelate Ca2+ displayed significantly decreased infectivity. This effect was denoted by reductions in both the proportion of rat heart myoblasts invaded by the parasite in vitro and the number of trypanosomes penetrating these host cells, the extents of which were BAPTA or Quin-2 concentration dependent. Consistent with these observations, inhibitory effects were also recorded when the parasite was pretreated with the calmodulin-binding phenothiazines trifluoperazine and chlorpromazine or with felodipine, a chemically different type of calmodulin antagonist, for as little as 5 min. In contrast, pretreatment with the Ca2+ ionophore ionomycin, which elevated Ca2+ levels in T. cruzi, significantly enhanced the infective capacity of the parasite. These results point to the existence of a Ca(2+)-dependent mechanism that regulates the invasive capacity of T. cruzi.
Yakubu
M A
MA
Department of Microbiology, Michigan State University, East Lansing 48824.
Majumder
S
S
Kierszenbaum
F
F
D000634:Aminoquinolines / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002147:Calmodulin / Q000037:antagonists & inhibitors*; D002460:Cell Line; D002478:Cells, Cultured; D004533:Egtazic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D005456:Fluorescent Dyes; D006321:Heart / Q000469:parasitology; D007202:Indicators and Reagents; D015759:Ionomycin / Q000494:pharmacology*; D051381:Rats; D014349:Trypanosoma cruzi / Q000187:drug effects* / Q000472:pathogenicity*
D000634:Aminoquinolines; D002147:Calmodulin; D005456:Fluorescent Dyes; D007202:Indicators and Reagents; D004533:Egtazic Acid; D015759:Ionomycin; C025603:1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid; C035739:Quin2; D002118:Calcium