The B[a]P-increased intercellular communication via translocation of connexin-43 into gap junctions reduces apoptosis

Journal Article · Thu Jan 14 23:00:00 EST 2010 · Toxicology and Applied Pharmacology

DOI:https://doi.org/10.1016/j.taap.2009.10.012· OSTI ID:21344844

Tekpli, X ^[1]; Rivedal, E ^[2]; Gorria, M ^[1]; Landvik, N E ^[3]; Rissel, M; Dimanche-Boitrel, M -T; Baffet, G ^[1]; Holme, J A ^[3]; Lagadic-Gossmann, D ^[1]

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1. EA 4427 SeRAIC, Equipe labellisee Ligue contre le Cancer, IFR 140, Universite de Rennes 1, Rennes (France)
2. Department of Cancer Prevention, Institute for Cancer Research, Norwegian Radium Hospital, Montebello, N-0310 Oslo (Norway)
3. Division of Environmental Medicine, Norwegian Institute of Public Health, Oslo (Norway)

Gap junctions are channels in plasma membrane composed of proteins called connexins. These channels are organized in special domains between cells, and provide for direct gap junctional intercellular communication (GJIC), allowing diffusion of signalling molecules < 1 kD. GJIC regulates cell homeostasis and notably the balance between proliferation, cell cycle arrest, cell survival and apoptosis. Here, we have investigated benzo[a]pyrene (B[a]P) effects on GJIC and on the subcellular localization of the major protein of gap junction: connexin-43 (Cx43). Our results showed that B[a]P increased GJIC between mouse hepatoma Hepa1c1c7 cells via translocation of Cx43 from Golgi apparatus and lipid rafts into gap junction plaques. Interestingly, inhibition of GJIC by chlordane or small interference RNA directed against Cx43 enhanced B[a]P-induced apoptosis in Hepa1c1c7 cells. The increased apoptosis caused by inhibition of GJIC appeared to be mediated by ERK/MAPK pathway. It is suggested that B[a]P could induce transfer of cell survival signal or dilute cell death signal via regulation of ERK/MAPK through GJIC.

• OSTI ID: 21344844
• Journal Information: Toxicology and Applied Pharmacology, Journal Name: Toxicology and Applied Pharmacology Journal Issue: 2 Vol. 242; ISSN TXAPA9; ISSN 0041-008X
• Country of Publication: United States
• Language: English

Related Subjects

60 APPLIED LIFE SCIENCES
ANIMALS
APOPTOSIS
AROMATICS
CARCINOMAS
CELL CONSTITUENTS
CELL PROLIFERATION
CHOLESTEROL
COMMUNICATIONS
CONDENSED AROMATICS
DISEASES
ENDOPLASMIC RETICULUM
GOLGI COMPLEXES
HEPATOMAS
HOMEOSTASIS
HYDROCARBONS
HYDROXY COMPOUNDS
MAMMALS
MEMBRANE PROTEINS
MICE
NEOPLASMS
NUCLEIC ACIDS
ORGANIC COMPOUNDS
POLYCYCLIC AROMATIC HYDROCARBONS
PROTEINS
RECEPTORS
RNA
RODENTS
STEROIDS
STEROLS
VERTEBRATES