Activation of the mitochondrial caspase pathway and subsequent calpain activation in monkey RPE cells cultured under zinc depletion.

ABSTRACT:

Purpose

Decreased zinc levels in the macula are reported in patients with age-related macular degeneration, and the zinc chelator N,N,N',N'-tetrakis (2- pyridylmethyl) ethylenediamine) (TPEN) causes death of human retinal pigment epithelial (RPE) cells. The purpose of the present study was to investigate signal transduction pathways during cell death initiated by TPEN, using monkey RPE cells.

Methods

RPE cells were cultured with TPEN. Activation of calpains and caspases, and proteolysis of their substrates were detected by immunoblotting. Incubation of calpain inhibitor SNJ-1945 or caspase inhibitor z-VAD-fmk was used to confirm activation of specific proteases.

Results

TPEN caused a time-dependent decrease in viable RPE cells. Cell death was accompanied by activation

SUBMITTER: Nakajima E 

PROVIDER: S-EPMC3890765 | biostudies-literature | 2014 Jan

REPOSITORIES: biostudies-literature