Hypoxia-inducible factor-lα increase is an early and sensitive marker of lung cells responding to benzo[a]pyrene.
J Environ Pathol Toxicol Oncol
; 31(4): 335-47, 2012.
Article
em En
| MEDLINE
| ID: mdl-23394446
ABSTRACT
Hypoxia inducible factor-1α (HIF-lα) is a central regulator of tumor survival and metastasis, responsible for metabolic adaptation to hypoxic conditions and promotion of angiogenesis. It has been also shown to respond to non-hypoxic stimuli, such as growth factors and moderate oxidative stress. We examined the protein levels of HIF-lα in A549 human lung cells exposed to the typical carcinogen benzo[a]pyrene (B[a]P). Our results revealed that B[a]P, at low, non-cytotoxic concentrations, induced a transient increase of nuclear HIF-lα and its target, GLUT1. HIF-lα upregulation was partly mediated by Akt kinase and coincided with increased nuclear levels of the redox-sensitive marker, nuclear factor erythroid 2-related factor-2 (NrF-2). B[a]P-induced HIF-lα was also detected during serum depletion or treatment with the hypoxia-mimicking agent, CoCl2. In addition, exposure of A549 cells to B[a]P containing diesel exhaust particles enhanced HIF-lα accumulation, probably due to the presence of additional carcinogenic compounds. B[a]P-induced increase of HIF-lα was further confirmed in normal rat and human lung fibroblasts. Our findings indicate that HIF-lα stimulation may act as an early and sensitive marker of exposure to low, non-cytotoxic concentrations of B[a]P and/or other carcinogens.
Buscar no Google
Base de dados:
MEDLINE
Assunto principal:
Benzo(a)pireno
/
Subunidade alfa do Fator 1 Induzível por Hipóxia
/
Pulmão
Idioma:
En
Ano de publicação:
2012
Tipo de documento:
Article