RESUMO
The IκB kinase complex (IKK) is a key regulator of immune responses, inflammation, cell survival, and tumorigenesis. The prosurvival function of IKK centers on activation of the transcription factor NF-κB, whose target gene products inhibit caspases and prevent prolonged JNK activation. Here, we report that inactivation of the BH3-only protein BAD by IKK independently of NF-κB activation suppresses TNFα-induced apoptosis. TNFα-treated Ikkß(-/-) mouse embryonic fibroblasts (MEFs) undergo apoptosis significantly faster than MEFs deficient in both RelA and cRel due to lack of inhibition of BAD by IKK. IKK phosphorylates BAD at serine-26 (Ser26) and primes it for inactivation. Elimination of Ser26 phosphorylation promotes BAD proapoptotic activity, thereby accelerating TNFα-induced apoptosis in cultured cells and increasing mortality in animals. Our results reveal that IKK inhibits TNFα-induced apoptosis through two distinct but cooperative mechanisms: activation of the survival factor NF-κB and inactivation of the proapoptotic BH3-only BAD protein.
Assuntos
Apoptose , Quinase I-kappa B/metabolismo , NF-kappa B/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Proteína de Morte Celular Associada a bcl/metabolismo , Animais , Fibroblastos/citologia , Quinase I-kappa B/genética , Camundongos , Camundongos Knockout , Fosforilação , Serina/metabolismo , Proteína de Morte Celular Associada a bcl/química , Proteína de Morte Celular Associada a bcl/genética , Proteína bcl-X/metabolismoRESUMO
The concentrations of 16 polycyclic aromatic hydrocarbons (PAHs) in water and sediment samples collected from 12 locations in Gao-ping River, Taiwan were analyzed. Molecular ratios and principal component analysis (PCA) were used to characterize the possible pollution sources. Concentrations of total 16 PAHs (SigmaPAHs) in water samples ranged from below method detection limits (Assuntos
Sedimentos Geológicos/química
, Hidrocarbonetos Policíclicos Aromáticos/análise
, Poluentes Químicos da Água/análise
, Indústria Química
, Monitoramento Ambiental
, Petróleo
, Rios
, Taiwan
, Emissões de Veículos