title: The role of G protein coupled receptor-mediated signaling in the biological properties of Acanthamoeba castellanii of the T4 genotype.
abstract: Despite advances in antimicrobial chemotherapy and supportive care, the prognosis of Acanthamoeba infections remains poor, suggesting that new targets are needed that can affect parasite survival and host-pathogen interactions. G proteins and their coupled receptors are well known regulators of a variety of cellular functions. The overall aim of the present study was to study the role of G-protein coupled receptor, β adrenergic receptor on the biology and pathogenesis of keratitis isolate of Acanthamoeba castellanii of the T4 genotype. Inhibition of β adrenergic receptor using antagonist, propranolol had detrimental effects on the extracellular proteolytic activities A. castellanii as determined using zymographic assays. Conversely, β adrenergic receptor agonist, isoprenaline showed increased proteases. Interestingly, β adrenergic receptor inhibition affected A. castellanii growth (using amoebistatic assays), viability (using amoebicidal assays by measuring uptake of Trypan blue) and encystation as determined by trophozoite transformation into the cyst form. Pre-treatment of parasites with propranolol hampered A. castellanii-mediated human brain microvascular endothelial cell cytotoxicity, as measured by the lacatate dehydrogenase release. The aforementioned findings suggest that G-protein coupled receptor, β adrenergic receptor-mediated signaling in A. castellanii biology and pathogenesis may offer new pharmacological targets.
authors.affiliation: Department of Biological and Biomedical Sciences, Aga Khan University, Karachi, Pakistan.
authors.forename: Yousuf
authors.initials: Y
authors.lastname: Aqeel
authors.affiliation: Department of Biological and Biomedical Sciences, Aga Khan University, Karachi, Pakistan.
authors.forename: Ruqaiyyah
authors.initials: R
authors.lastname: Siddiqui
authors.affiliation: Department of Biological and Biomedical Sciences, Aga Khan University, Karachi, Pakistan.
authors.forename: Zainab
authors.initials: Z
authors.lastname: Manan
authors.affiliation: Department of Biological and Biomedical Sciences, Aga Khan University, Karachi, Pakistan. Electronic address: naveed5438@gmail.com.
authors.forename: Naveed Ahmed
authors.initials: NA
authors.lastname: Khan
mesh_terms: D048248:Acanthamoeba castellanii / Q000145:classification / Q000235:genetics / Q000254:growth & development / Q000502:physiology*; D000318:Adrenergic beta-Agonists / Q000378:metabolism; D000319:Adrenergic beta-Antagonists / Q000378:metabolism; D002470:Cell Survival; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000469:parasitology / Q000502:physiology; D005838:Genotype; D006801:Humans; D007545:Isoproterenol; D010447:Peptide Hydrolases / Q000378:metabolism; D011433:Propranolol / Q000378:metabolism; D059748:Proteolysis; D011943:Receptors, Adrenergic, beta / Q000378:metabolism*; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism*; D015398:Signal Transduction; D033761:Spores, Protozoan / Q000254:growth & development
chemical_list: D000318:Adrenergic beta-Agonists; D000319:Adrenergic beta-Antagonists; D011943:Receptors, Adrenergic, beta; D043562:Receptors, G-Protein-Coupled; D011433:Propranolol; D010447:Peptide Hydrolases; D007545:Isoproterenol
keywords: Acanthamoeba castellanii; Cytotoxicity; G protein couple receptors; Viability; Zymographic assays; β adrenergic receptor