Serum pantetheinase/vanin levels regulate erythrocyte homeostasis and severity of malaria

The American Journal of Pathology
Samuel RommelaereP Naquet

Abstract

Tissue pantetheinase, encoded by the VNN1 gene, regulates response to stress, and previous studies have shown that VNN genes contribute to the susceptibility to malaria. Herein, we evaluated the role of pantetheinase on erythrocyte homeostasis and on the development of malaria in patients and in a new mouse model of pantetheinase insufficiency. Patients with cerebral malaria have significantly reduced levels of serum pantetheinase activity (PA). In mouse, we show that a reduction in serum PA predisposes to severe malaria, including cerebral malaria and severe anemia. Therefore, scoring pantetheinase in serum may serve as a severity marker in malaria infection. This disease triggers an acute stress in erythrocytes, which enhances cytoadherence and hemolysis. We speculated that serum pantetheinase might contribute to erythrocyte resistance to stress under homeostatic conditions. We show that mutant mice with a reduced serum PA are anemic and prone to phenylhydrazine-induced anemia. A cytofluorometric and spectroscopic analysis documented an increased frequency of erythrocytes with an autofluorescent aging phenotype. This is associated with an enhanced oxidative stress and shear stress-induced hemolysis. Red blood cell transfer an...Continue Reading

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Citations

Nov 26, 2015·Current Opinion in Immunology·Philippe NaquetFranck Galland
Mar 30, 2018·Mammalian Genome : Official Journal of the International Mammalian Genome Society·Hong Ming HuangGaetan Burgio
Dec 3, 2020·International Journal of Molecular Sciences·Aleksandra CzumajEwa Stelmanska
Apr 3, 2020·Progress in Lipid Research·Philippe NaquetRoberta Leonardi
May 25, 2021·Emerging Topics in Life Sciences·Douglas Fraser-Pitt, Derry Mercer
Sep 16, 2017·Analytical Chemistry·Yiming HuHuimin Ma

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