losartan-potassium and Trypanosomiasis

Trypanosoma carassii is a flagellated bloodstream parasite of cyprinid fish with pathogenesis manifesting primarily as anemia in experimentally infected fish. This anemia is characterized by decreases in the number of circulating red blood cells (RBCs) during peak parasitemia. We examined changes in the key blood metrics and expression of genes known to be important in the regulation of erythropoiesis. Increasing parasitemia was strongly correlated with an overall decrease in the total number of circulating RBCs. Gene expression of key erythropoiesis regulators (EPO, EPOR, GATA1, Lmo2, and HIFα) and proinflammatory cytokines (IFNγ and TNFα) were measured and their expressions differed from those in fish made anemic by injections of phenylhydrazine (PHZ). Significant upregulation of pro-erythropoietic genes was observed in PHZ-induced anemia, but not during peak parasitic infection. Previously, we reported on functional characterization of goldfish erythropoietin (rgEPO) and its ability to induce survival and differentiation of erythroid progenitor cells in vitro. Treatment of goldfish during the infection with rgEPO reduced the severity of anemia but failed to fully prevent the onset of the anemic state in infected fish. Proinflammatory cytokines have been implicated in the suppression of erythropoiesis during trypanosomiasis, specifically the cytokines TNFα, IFNγ, and IL-1β. Analysis of key proinflammatory cytokines revealed that mRNA levels of IFNγ and TNFα were upregulated in response to infection, but only TNFα increased in response to PHZ treatment. Synergistic activity of the proinflammatory cytokines may be required to sustain prolonged anemia. These findings provide insight into the relationship between T. carassii and host anemia and suggest that T. carassii may directly or indirectly suppress host erythropoiesis.

Topics: Anemia; Animals; Cytokines; Erythrocyte Count; Erythropoiesis; Erythropoietin; GATA1 Transcription Factor; Gene Expression Regulation; Goldfish; Interferon-gamma; LIM Domain Proteins; Parasitemia; Phenylhydrazines; Receptors, Erythropoietin; RNA, Messenger; Trypanosoma; Trypanosomiasis; Tumor Necrosis Factor-alpha

A bovine cDNA encoding erythropoietin (Epo) was isolated by polymerase chain reaction (PCR) amplification and screening of a bovine kidney cDNA library. The sequenced cDNA has a length of 1312 bp and an open reading frame that encodes a predicted 192-amino-acid (aa) protein, including a putative signal sequence of 25 aa. A mature protein of 167 aa (18.4 kDa) results upon cleavage of the putative signal peptide. The deduced bovine mature Epo peptide exhibits 96, 88, 83, 82 and 79% sequence identity to that of sheep, swine, human, monkey and rat, respectively. The expression of the bovine Epo gene in tissues from a severely anemic calf, bovine fetus and a healthy steer was analysed by a competitive RT-PCR method. In kidneys of the severely anemic calf, Epo mRNA levels increased 60-fold relative to that from the kidneys of the healthy steer. Epo mRNA levels were threefold higher in the liver of the bovine fetus than that in its kidneys. Low levels of Epo transcripts were detected in RNA from spleen of the severely anemic calf and the bovine fetus. No Epo transcripts were detectable in spleen from the healthy steer.

Topics: Amino Acid Sequence; Anemia; Animals; Base Sequence; Blotting, Northern; Cattle; Cloning, Molecular; DNA, Complementary; Erythropoietin; Fetus; Gene Expression Regulation, Developmental; Kidney; Liver; Male; Mammals; Molecular Sequence Data; Polymerase Chain Reaction; Sequence Homology, Amino Acid; Tissue Distribution; Transcription, Genetic; Trypanosomiasis