NHE-1 relocation outside cholesterol-rich membrane microdomains is associated with its benzo[a]pyrene-related apoptotic function.
Cell Physiol Biochem
; 29(5-6): 657-66, 2012.
Article
em En
| MEDLINE
| ID: mdl-22613966
ABSTRACT
BACKGROUND:
Polycyclic aromatic hydrocarbons (PAHs), such as benzo[a]pyrene (B[a]P), are ubiquitous toxic environmental pollutants capable of inducing cell death. Intracellular pH plays a key role in the regulation of cell survival and death. Our previous works have demonstrated that intracellular alkalinization mediated by Na(+)/H(+) exchanger 1 (NHE-1) is a critical event involved in B[a]P-induced apoptosis. The aim of this study was to further elucidate the mechanisms of NHE-1 activation upon B[a]P exposure.METHODS:
We tested the effects of plasma membrane cholesterol enrichment or depletion on B[a]P-induced NHE-1 activation related to apoptosis. We isolated cholesterol-rich plasma membrane microdomains to assess NHE-1 submembrane location and immunoprecipitated NHE-1 from the different sub-membrane fractions obtained to examine NHE-1 protein interactions during B[a]P-induced apoptosis.RESULTS:
We found that NHE-1 is preferentially located in cholesterol-rich microdomains and that B[a]P activates NHE-1 via its relocation and binding of calmodulin outside these specialized plasma membrane microstructures; these events are necessary for the execution of the apoptosis-related intracellular alkalinization.CONCLUSION:
Plasma membrane location of NHE-1 affects its protein interactions and apoptotic function.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Benzo(a)pireno
/
Colesterol
/
Apoptose
/
Trocadores de Sódio-Hidrogênio
Tipo de estudo:
Risk_factors_studies
Limite:
Animals
Idioma:
En
Ano de publicação:
2012
Tipo de documento:
Article