title: Hypoxia-inducible factor-lα increase is an early and sensitive marker of lung cells responding to benzo[a]pyrene.
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.
authors: Division of Animal and Human Physiology, Department of Biology, University of Athens, 15784 Panepistimiopolis, Ilissia, Athens, Greece.
authors: Olga
authors: O
authors: Mavrofrydi
authors: Panagiota
authors: P
authors: Papazafiri
mesh_terms: D001564:Benzo(a)pyrene / Q000633:toxicity*; D015415:Biomarkers; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism*; D008168:Lung / Q000187:drug effects*; D051267:NF-E2-Related Factor 2 / Q000032:analysis; D019869:Phosphatidylinositol 3-Kinases / Q000502:physiology; D051057:Proto-Oncogene Proteins c-akt / Q000502:physiology
chemical_list: D015415:Biomarkers; C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D051267:NF-E2-Related Factor 2; C495635:NFE2L2 protein, human; D001564:Benzo(a)pyrene; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt