• Home
  • Search Results
  • Characterization of cellular protective effects of ATP13A2/PARK9 expression and alterations resulting from pathogenic mutants.

Characterization of cellular protective effects of ATP13A2/PARK9 expression and alterations resulting from pathogenic mutants.

Journal of neuroscience research (2012-08-01)
Jason P Covy, Elisa A Waxman, Benoit I Giasson
ABSTRACT

Mutations in ATP13A2, which encodes a lysosomal P-type ATPase of unknown function, cause an autosomal recessive parkinsonian syndrome. With mammalian cells, we show that ATP13A2 expression protects against manganese and nickel toxicity, in addition to proteasomal, mitochondrial, and oxidative stress. Consistent with a recessive mode of inheritance of gene defects, disease-causing mutations F182L and G504R are prone to misfolding and do not protect against manganese and nickel toxicity because they are unstable as a result of degradation via the endoplasmic reticulum-associated degradation (ERAD)-proteasome system. The protective effects of ATP13A2 expression are not due to inhibition of apoptotic pathways or a reduction in typical stress pathways, insofar as these pathways are still activated in challenged ATP13A2-expressing cells; however, these cells display a dramatic reduction in the accumulation of oxidized and damaged proteins. These data indicate that, contrary to a previous suggestion, ATP13A2 is unlikely to convey cellular resilience simply by acting as a lysosomal manganese transporter. Consistent with the recent identification of an ATP13A2 recessive mutation in Tibetan terriers that develop neurodegeneration with neuronal ceroid lipofucinoses, our data suggest that ATP13A2 may function to import a cofactor required for the function of a lysosome enzyme(s).

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Nickel(II) chloride, 98%
Sigma-Aldrich
Manganese(II) chloride tetrahydrate, ReagentPlus®, ≥99%
Sigma-Aldrich
Nickel(II) chloride hexahydrate, 99.9% trace metals basis
Sigma-Aldrich
Manganese(II) chloride solution, BioReagent, for molecular biology, storage temp.: room temp
Sigma-Aldrich
Manganese(II) chloride tetrahydrate, ACS reagent, ≥98%
Sigma-Aldrich
Nickel(II) chloride hexahydrate, ReagentPlus®
Sigma-Aldrich
Manganese(II) chloride, powder and chunks, ≥99% trace metals basis
Sigma-Aldrich
Manganese(II) chloride tetrahydrate, BioReagent, suitable for insect cell culture
Sigma-Aldrich
Manganese(II) chloride tetrahydrate, 99.99% trace metals basis
Sigma-Aldrich
Anti-Actin Antibody, clone C4, ascites fluid, clone C4, Chemicon®
Sigma-Aldrich
Nickel(II) chloride, anhydrous, powder, 99.99% trace metals basis
Sigma-Aldrich
Nickel(II) chloride hexahydrate, BioReagent, suitable for cell culture
Sigma-Aldrich
Manganese(II) chloride tetrahydrate, meets USP testing specifications
Sigma-Aldrich
Nickel(II) chloride hexahydrate, puriss. p.a., ≥98%
Sigma-Aldrich
Manganese(II) chloride, beads, 98%
Sigma-Aldrich
Nickel(II) chloride hexahydrate, 99.999% trace metals basis
Sigma-Aldrich
Manganese(II) chloride 0.1 M solution
Sigma-Aldrich
Manganese(II) chloride tetrahydrate, BioUltra, for molecular biology, ≥99.0% (KT)
Sigma-Aldrich
Manganese(II) chloride, AnhydroBeads, −10 mesh, 99.99% trace metals basis
Sigma-Aldrich
Manganese(II) chloride, flakes, 97%
Sigma-Aldrich
Nickel(II) chloride hydrate, 99.95% trace metals basis
Sigma-Aldrich
Manganese(II) chloride, AnhydroBeads, −10 mesh, 99.999% trace metals basis
Sigma-Aldrich
Anti-ATP13A2 (C-terminal) antibody produced in rabbit, ~1.5 mg/mL, affinity isolated antibody, buffered aqueous solution
Sigma-Aldrich
Anti-ATP13A2 antibody produced in rabbit, ~1 mg/mL, affinity isolated antibody, buffered aqueous solution