RGD Reference Report - Identification of the couple GSK3alpha/c-Myc as a new regulator of hexokinase II in benzopyrene-induced apoptosis. - Rat Genome Database

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Identification of the couple GSK3alpha/c-Myc as a new regulator of hexokinase II in benzopyrene-induced apoptosis.

Authors: Dendele, B  Tekpli, X  Sergent, O  Dimanche-Boitrel, MT  Holme, JA  Huc, L  Lagadic-Gossmann, D 
Citation: Dendele B, etal., Toxicol In Vitro. 2012 Feb;26(1):94-101. doi: 10.1016/j.tiv.2011.11.001. Epub 2011 Nov 12.
RGD ID: 7240569
Pubmed: PMID:22100782   (View Abstract at PubMed)
DOI: DOI:10.1016/j.tiv.2011.11.001   (Journal Full-text)

The early apoptotic events induced by environmental pollutants with carcinogenic properties are poorly understood. Here, we focus on the early cytotoxic effects of benzo[a]pyrene (B[a]P). In F258 rat hepatic epithelial cells, B[a]P induces intrinsic apoptosis via a mitochondrial dysfunction characterized by the release of hexokinase II (HKII) from the mitochondria. Cancer cells often have an anomalous cell energy metabolism; since HKII dysfunction regulates B[a]P-induced apoptosis in F258 cells, but may also alter cell energy metabolism, HKII release from the mitochondria may represent an important B[a]P-related carcinogenic issue. Thus in the present study, we aimed at deciphering the mechanisms underlying HKII dysfunction upon B[a]P exposure. We show that while glycogen synthase kinase 3 beta (GSK3beta) regulated the expression of HKII at the transcriptional level, glycogen synthase kinase 3 alpha (GSK3alpha) was involved in B[a]P-induced apoptosis via a decrease in c-Myc expression. The reduced level of c-Myc caused the relocation of HKII from the mitochondria to the cytosol, thereby being involved in the formation of reactive oxygen species and apoptosis. In conclusion, we show that the couple GSK3alpha/c-Myc plays a key role in B[a]P-induced early apoptotic cell signaling via HKII dysfunction.

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
negative regulation of epithelial cell apoptotic process  IMP 7240569 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Myc  (MYC proto-oncogene, bHLH transcription factor)


Additional Information