Opposite Effects of Lithium on Proximal and Distal Caspases of Immature and Mature Primary Neurons Correlate with Earlier Paradoxical Actions ... View Full Text


Ontology type: schema:ScholarlyArticle     


Article Info

DATE

2001-12

AUTHORS

Neville Marks, Mariko Saito, Maurice Green, Margaret A. Reilly, Austin J. Yang, Kristen Ditaranto, Martin J. Berg

ABSTRACT

To provide an explanation for earlier paradoxical findings of lithium on survival of mature and immature neurons, this study monitors changes in cytosolic caspases in rat cerebellar granule cells (CGC) grown 2-7 days in vitro (DIV), or in murine E-17 cortical neurons. Data show Li+ protects mature 7-DIV CGC parallel to a decrease in proximal and distal caspases but increases levels for immature 2-DIV-CGC or E-17 cortical neurons. Caspases mirror viability based on morphological analyses (dye uptake, phase-contrast, DNA fragmentation), and suggest protection occurs by suppressing activation of a cascade resulting in distal effectors that destroy proteins essential for neuronal survival. Protection was dose-dependent with EC50 3.0 mM and extended to 64 h in K+-serum deprived apoptotic media. Neuronal extracts contain a spectrum of proximal (-2, -8, -9) and distal (-3, -6) caspases sensitive to Li+ on assay with preferred peptide substrates and by immunoblotting. The lack of direct effect on activated cytosols indicates Li+ acts upstream only on intact cells, at sites for recruitment of pivotal procaspases. Alterations of procaspase-9 p46 and membrane-bound cytochrome c (Apaf-1) point to interaction with an intrinsic Mt-mediated pathway as one of the targets. The opposite effects on caspases and viability of immature or embryological neurons point to existence of alternative pathways that alter during neurite outgrowth suggesting the use of Li+ as a probe to unravel events relevant to neurogenesis. More... »

PAGES

1311-1320

References to SciGraph publications

Identifiers

URI

http://scigraph.springernature.com/pub.10.1023/a:1014249517926

DOI

http://dx.doi.org/10.1023/a:1014249517926

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1052990948

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/11885783


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