Hemoglobin catabolism and host-parasite heme balance in chloroquine-sensitive and chloroquine-resistant Plasmodium berghei infections.
Catabolism of host hemoglobin by the malaria parasite liberates required amino acid precursors, but is also releases large amounts of potentially toxic heme that accumulates in parasite food vacuoles during intra-erythrocytic development. The schizonticidal drug chloroquine binds to free heme with high affinity and is concentrated in parasite food vacuoles. To better understand the disposition of heme within the host-parasite complex, we studied the balance of hemoglobin and heme in Plasmodium berghei-infected reticulocytes in the rat and compared this process in chloroquine-sensitive (CS) and chloroquine-resistant (CR) parasites. We found that CS P. berghei parasites have 1.5-fold more heme than CR parasites isolated from rats, and that CS P. berghei-infected reticulocytes accumulate more chloroquine than CR P. berghei-infected reticulocytes. Despite these differences in parasite heme content, the decrease in host cell hemoglobin content and the rate of free amino acid generation within the host-parasite complex is similar in CS and CR P. berghei-infected rat reticulocytes. The heme content of the infected reticulocyte-parasite complex decreases with increasing parasitemia but to a lesser extent than expected for the decrease in hemoglobin. Furthermore, the decrease in host-parasite heme is accelerated in the CR P. berghei infection compared with the CS P. berghei infection. Therefore, hemoglobin catabolism by malaria parasites is associated with the overall loss of heme from the host-parasite complex and with variable deposition of heme within parasites.(ABSTRACT TRUNCATED AT 250 WORDS)
Wood
P A
PA
Stratton Veterans Administration Medical Center, Albany, New York.
Eaton
J W
JW
D000704:Analysis of Variance; D000818:Animals; D002738:Chloroquine / Q000097:blood / Q000378:metabolism / Q000494:pharmacology*; D004351:Drug Resistance; D004912:Erythrocytes / Q000737:chemistry / Q000378:metabolism / Q000469:parasitology; D006418:Heme / Q000032:analysis / Q000378:metabolism*; D006454:Hemoglobins / Q000032:analysis / Q000378:metabolism*; D006790:Host-Parasite Interactions; D008288:Malaria / Q000097:blood* / Q000469:parasitology; D008297:Male; D051379:Mice; D010962:Plasmodium berghei / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012156:Reticulocytes / Q000737:chemistry / Q000378:metabolism / Q000469:parasitology
D006454:Hemoglobins; D006418:Heme; D002738:Chloroquine