ApoL1 Overexpression Drives Variant-Independent Cytotoxicity.

ABSTRACT: Coding variants in the APOL1 gene are associated with kidney diseases in African ancestral populations; yet, the underlying biologic mechanisms remain uncertain. Variant-dependent autophagic and cytotoxic cell death have been proposed as pathogenic pathways mediating kidney injury. To examine this possibility, we conditionally expressed APOL1-G0 (reference), -G1, and -G2 (variants) using a tetracycline-regulated system in HEK293 cells. Autophagy was monitored biochemically and cell death was measured using multiple assays. We measured intracellular Na⁺ and K⁺ content with atomic absorption spectroscopy and APOL1-dependent currents with whole-cell patch clamping. Neither reference nor variant APOL1s induced autophagy. At high expression levels, APOL1-G0, -G1, an

SUBMITTER: O'Toole JF 

PROVIDER: S-EPMC5827587 | biostudies-literature | 2018 Mar

REPOSITORIES: biostudies-literature