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1.
Front Cell Infect Microbiol ; 13: 1150054, 2023.
Article in English | MEDLINE | ID: mdl-37360530

ABSTRACT

The protozoan disease is a major global health concern. Amoebiasis, leishmaniasis, Chagas disease, and African sleeping sickness affect several million people worldwide, leading to millions of deaths annually and immense social and economic problems. Iron is an essential nutrient for nearly all microbes, including invading pathogens. The majority of iron in mammalian hosts is stored intracellularly in proteins, such as ferritin and hemoglobin (Hb). Hb, present in blood erythrocytes, is a very important source of iron and amino acids for pathogenic microorganisms ranging from bacteria to eukaryotic pathogens, such as worms, protozoa, yeast, and fungi. These organisms have developed adequate mechanisms to obtain Hb or its byproducts (heme and globin) from the host. One of the major virulence factors identified in parasites is parasite-derived proteases, essential for host tissue degradation, immune evasion, and nutrient acquisition. The production of Hb-degrading proteases is a Hb uptake mechanism that degrades globin in amino acids and facilitates heme release. This review aims to provide an overview of the Hb and heme-uptake mechanisms utilized by human pathogenic protozoa to survive inside the host.


Subject(s)
Parasites , Animals , Humans , Parasites/metabolism , Hemoglobins/metabolism , Heme/metabolism , Endopeptidases , Peptide Hydrolases , Iron/metabolism , Mammals/metabolism
2.
Dev Growth Differ ; 53(5): 704-14, 2011 Jun.
Article in English | MEDLINE | ID: mdl-21671918

ABSTRACT

The activation of sea urchin eggs at fertilization provides an ideal system for studying the molecular events involved in cellular activation. Rho GTPases, which are key signaling enzymes in eukaryotes, are involved in sustaining the activation of sea urchin eggs; however, their downstream effectors have not yet been characterized. In somatic cells, RhoA regulates a serine/threonine kinase known as Rho-kinase (ROCK). The activity of ROCK in early sea urchin development has been inferred, but not tested directly. A ROCK gene was identified in the sea urchin (Strongylocentrotus purpuratus) genome and the sequence of its cDNA determined. The sea urchin ROCK (SpROCK) sequence predicts a protein of 158 kDa with >72% and 45% identities with different protein orthologues of the kinase catalytic domain and the complete protein sequence, respectively. SpROCK mRNA levels are high in unfertilized eggs and decrease to 35% after 15 min postfertilization and remain low up to the 4 cell stage. Antibodies to the human ROCK-I kinase domain revealed SpROCK to be concentrated in the cortex of eggs and early embryos. Co-immunoprecipitation assays indicate that RhoA and SpROCK are physically associated. This association is destroyed by treatment with the C3 exoenzyme and with the ROCK antagonist H-1152. H-1152 also inhibited DNA synthesis in embryos. We conclude that the Rho-dependent signaling pathway, via SpROCK, is essential for early embryonic development.


Subject(s)
Embryonic Development/physiology , Ovum/enzymology , RNA, Messenger/metabolism , Strongylocentrotus purpuratus/embryology , Strongylocentrotus purpuratus/enzymology , rho-Associated Kinases/metabolism , 1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine/analogs & derivatives , Animals , Base Sequence , DNA, Complementary/genetics , Embryo, Nonmammalian/enzymology , Enzyme Activation/physiology , Immunoprecipitation , Molecular Sequence Data , Sequence Analysis, DNA , rhoA GTP-Binding Protein/metabolism
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