CHO cells expressing the human P5 ATPase ATP13A2 are more sensitive to the toxic effects of herbicide paraquat

DE TEZANOS PINTO FELICITAS; CORRADI GERARDO RAUL; DE LA HERA DIEGO P; ADAMO HUGO PEDRO

NEUROCHEMISTRY INTERNATIONAL

PERGAMON-ELSEVIER SCIENCE LTD

Lugar: Amsterdam; Año: 2012 vol. 60 p. 243 - 248

0197-0186

P-ATPases are membrane transporters energized by ATP. The subfamily of P5-ATPases is the least studiedP-ATPases and the ion substrate specificity of the P5 subfamily is not known. Mutations of thehumanP5ATPasegene ATP13A2 has been shown to underlie a form of Parkinson disease (PD). We investigated the linkbetween ATP13A2 and environmental factors related to PD development. Increasing concentrations ofthe synthetic polyamine analog paraquat induced a greater cytotoxic effect over CHO cells expressingATP13A2. Paraquat-toxicity was associated with increased production of cellular reactive oxygen speciesand this increment was reversed by the natural polyamine spermidine. Acridine orange fluorescence intensitysuggested that ATP13A2 induced the expansion of acidic vesicles that become more alkaline uponexternal addition of spermidine. Polyamine uptake is proposed to be initiated by a plasma membrane carrierfollowed by sequestration into acidic vesicles of the late endocytic compartment through an unidentifiedactive mechanism; because ATP13A2 is located in lysosomes and late endosomes, our results open thepossibility that ATP13A2 could be one of those active transporters capable of transporting polyamines likespermidine as well as its toxic analog paraquat.