Altered calcium homeostasis and membrane destabilization in erythrocytes of hamsters infected with Leishmania donovani.
Homeostatic mechanisms regulating intracellular concentrations of Ca2+ at a low level are prerequisites for maintaining the integral and cytoskeletal structure of erythrocytes under normal physiological conditions. The present study was undertaken to assess the contribution of Ca2+ homeostasis in modifying red-cell stability in hamsters, during the anaemia caused by Leishmania donovani. Erythrocytes from the infected animals became increasingly fragile as infection progressed. This fragility may be the result of a gradual change in membrane permeability, as indicated by enhanced uptake of 45Ca2+. The increase in cytosolic Ca2+ and decrease in membrane-bound Ca2+ observed indicate the release of Ca2+ from the membrane store, leading to [Ca2+]i accumulation in the later stages of the post-infection period. Decline in the efficacy of Ca(2+)-effluxing enzyme may also contribute to the enhanced [Ca2+]i level, with subsequent degradation of membrane proteins in the erythrocytes of the infected animals. Marked inhibition of proteolytic degradation by the Ca(2+)-dependent thiol protease inhibitor leupeptin, with concomitant thiol depletion, indicates the involvement of Ca(2+)-induced thiol protease in the observed degradation of membrane proteins. The results indicate that an altered Ca2+ homeostasis in erythrocytes following leishmanial infection causes enhanced cellular accumulation of Ca2+, which in turn may lead to haemolysis in experimental visceral leishmaniasis.
Sen
G
G
Department of Physiology, Indian Institute of Chemical Biology, Jadavpur, Calcutta, India.
Ghosal
J
J
Naskar
K
K
Biswas
T
T
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002463:Cell Membrane Permeability / Q000502:physiology; D006224:Cricetinae; D004910:Erythrocyte Membrane / Q000502:physiology; D004912:Erythrocytes / Q000378:metabolism / Q000469:parasitology*; D006706:Homeostasis / Q000502:physiology; D007893:Leishmania donovani; D007898:Leishmaniasis, Visceral / Q000378:metabolism*; D008565:Membrane Proteins / Q000502:physiology
D008565:Membrane Proteins; D002118:Calcium