The DOI matches its Crossref record; 43 of the 43 references it cites were found in a registry or an index.
Induction of HIF‐1α expression by intermittent hypoxia: Involvement of NADPH oxidase, Ca2+ signaling, prolyl hydroxylases, and mTOR
Open accessAbstract
Sleep‐disordered breathing with recurrent apnea (periodic cessation of breathing) results in chronic intermittent hypoxia (IH), which leads to cardiovascular and respiratory pathology. Molecular mechanisms underlying IH‐evoked cardio‐respiratory co‐morbidities have not been delineated. Mice with heterozygous deficiency of hypoxia‐inducible factor 1α (HIF‐1α) do not develop cardio‐respiratory responses to chronic IH. HIF‐1α protein expression and HIF‐1 transcriptional activity are induced by IH in PC12 cells. In the present study, we investigated the signaling pathways associated with IH‐evoked HIF‐1α accumulation. PC12 cells were exposed to aerobic conditions (20% O 2) or 60 cycles of IH (30 sec at 1.5% O 2 followed by 5 min at 20% O 2). Our results show that IH‐induced HIF‐1α accumulation is due to increased generation of ROS by NADPH oxidase. We further demonstrate that ROS‐dependent Ca 2+ signaling pathways involving phospholipase Cγ (PLCγ) and protein kinase C activation are required for IH‐evoked HIF‐1α accumulation. IH leads to activation of mTOR and S6 kinase (S6K) and rapamycin partially inhibited IH‐induced HIF‐1α accumulation. IH also decreased hydroxylation of HIF‐1α protein and anti‐oxidants as well as inhibitors of Ca+2 signaling prevented this response. Thus, both increased mTOR‐dependent HIF‐1α synthesis and decreased hydroxylase‐dependent HIF‐1α degradation contribute to IH‐evoked HIF‐1α accumulation. Following IH, HIF‐1α, and phosphorylated mTOR levels remained elevated during 90 min of re‐oxygenation despite re‐activation of prolyl hydroxylase. Rapamycin or cycloheximide, blocked increased HIF‐1α levels during re‐oxygenation indicating that mTOR‐dependent protein synthesis is required for the persistent elevation of HIF‐1α levels during re‐oxygenation. J. Cell. Physiol. 217: 674–685, 2008. © 2008 Wiley‐Liss, Inc.
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Cites
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HIFα Targeted for VHL-Mediated Destruction by Proline Hydroxylation: Implications for O 2 Sensing
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“In cells exposed to CH, decreased HIF-1a prolyl hydroxylation leads to decreased HIF-1a degradation (Ivan et al., 2001; Jaakkola et al., 2001; Yu et al., 2001; Kageyama et al., 2004).”
BackgroundNieto, F. J. (2000) · JAMA · doi:10.1001/jama.283.14.1829 · Cited by 3,369
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Cellular and developmental control of O 2 homeostasis by hypoxia-inducible factor 1α
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Cited by
Hypoxia-inducible factors and the response to hypoxic stress
Majmundar, A. J., Wong, W. J., & Simon, M. C. (2010) · Molecular Cell · doi:10.1016/j.molcel.2010.09.022 · Cited by 2,380
Regulation of Oxygen Homeostasis by Hypoxia-Inducible Factor 1
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Korbecki, J., Simińska, D., Gąssowska-Dobrowolska, M., Listos, J., Gutowska, I., Chlubek, D., & Baranowska-Bosiacka, I. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms221910701 · Cited by 380
Drager, L. F., Polotsky, V. Y., & Lorenzi-Filho, G. (2011) · Chest · doi:10.1378/chest.10-2223 · Cited by 322
Metadata
- Authors
- Yuan, G., Nanduri, J., Khan, S., Semenza, G. L., & Prabhakar, N. R.
- Venue
- Journal of Cellular Physiology
- Publisher
- Wiley
- Published
- 2008-07-23
- Volume
- 217
- Issue
- 3
- Pages
- 674-685
- ISSN
- 0021-9541 (ISSN-L)
- 1097-4652
- OpenAlex
- W1982030800
- Cited by
- 310
- References
- 43
- FWCI
- 12.47
- Type
- journal article
- Language
- en
- Open access
- green
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