RGD Reference Report - A new lactoferrin- and iron-dependent lysosomal death pathway is induced by benzopyrene in hepatic epithelial cells. - Rat Genome Database

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A new lactoferrin- and iron-dependent lysosomal death pathway is induced by benzopyrene in hepatic epithelial cells.

Authors: Gorria, M  Tekpli, X  Rissel, M  Sergent, O  Huc, L  Landvik, N  Fardel, O  Dimanche-Boitrel, MT  Holme, JA  Lagadic-Gossmann, D 
Citation: Gorria M, etal., Toxicol Appl Pharmacol. 2008 Apr 15;228(2):212-24. Epub 2008 Jan 3.
RGD ID: 2293326
Pubmed: PMID:18255115   (View Abstract at PubMed)
DOI: DOI:10.1016/j.taap.2007.12.021   (Journal Full-text)

While lysosomal disruption seems to be a late step of necrosis, a moderate lysosomal destabilization has been suggested to participate early in the apoptotic cascade. The origin of lysosomal dysfunction and its precise role in apoptosis or apoptosis-like process still needs to be clarified, especially upon carcinogen exposure. In this study, we focused on the implication of lysosomes in cell death induced by the prototype carcinogen benzo[a]pyrene (B[a]P; 50 nM) in rat hepatic epithelial F258 cells. We first demonstrated that B[a]P affected lysosomal morphology (increase in size) and pH (alkalinization), and that these changes were involved in caspase-3 activation and cell death. Subsequently, we showed that lysosomal modifications were partly dependent on mitochondrial dysfunction, and that lysosomes together with mitochondria participate in B[a]P-induced oxidative stress. Using two iron chelators (desferrioxamine and deferiprone) and siRNA targeting the lysosomal iron-binding protease lactoferrin, we further demonstrated that both lysosomal iron content and lactoferrin were required for caspase-3 activation and apoptosis-like cell death.



Gene Casp3 caspase 3 Rattus norvegicus