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ISSN Druckformat: 0731-8898
ISSN Online: 2162-6537
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Hypoxia-Inducible Factor-lα Increase is an Early and Sensitive Marker of Lung Cells Responding to Benzo[a]Pyrene
ABSTRAKT
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.
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