NHE-1 Relocation Outside Cholesterol-rich Membrane Microdomains is Associated with its Benzo[a]pyrene-related Apoptotic Function

Cellular Physiology and Biochemistry

关键词: NHE-1;    Cholesterol-rich-microdomains;    Apoptosis;    Benzo[a]pyrene;    Calmodulin;   

DOI  :  10.1159/000171027

学科分类：分子生物学，细胞生物学和基因

来源: S Karger AG

【 摘 要 】

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]Pinduced 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.

【 授权许可】

CC BY-NC-ND