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Cited by 186

The DOI matches its Crossref record; 9 of the 9 references it cites were found in a registry or an index.

Intermittent hypoxia degrades HIF-2α via calpains resulting in oxidative stress: Implications for recurrent apnea-induced morbidities

Open access
Nanduri, Jayasri, Wang, Ning, Yuan, Guoxiang, Khan, Shakil A., Souvannakitti, Dangjai, Peng, Ying-Jie, Kumar, Ganesh K., Garcia, Joseph A., Prabhakar, Nanduri R.·2009·Proceedings of the National Academy of Sciences
DOI 10.1073/pnas.0811018106
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Abstract

Intermittent hypoxia (IH) occurs in many pathological conditions including recurrent apneas. Hypoxia-inducible factors (HIFs) 1 and 2 mediate transcriptional responses to low O 2 . A previous study showed that HIF-1 mediates some of the IH-evoked physiological responses. Because HIF-2α is an orthologue of HIF-1α, we examined the effects of IH on HIF-2α, the O 2 -regulated subunit expression, in pheochromocytoma 12 cell cultures. In contrast to the up-regulation of HIF-1α, HIF-2α was down-regulated by IH. Similar down-regulation of HIF-2α was also seen in carotid bodies and adrenal medullae from IH-exposed rats. Inhibitors of calpain proteases (ALLM, ALLN) prevented IH-evoked degradation of HIF-2α whereas inhibitors of prolyl hydroxylases or proteosome were ineffective. IH activated calpain proteases and down-regulated the endogenous calpain inhibitor calpastatin. IH-evoked HIF-2α degradation led to inhibition of SOD2 transcription, resulting in oxidative stress. Over-expression of transcriptionally active HIF-2α prevented IH-evoked oxidative stress and restored SOD2 activity. Systemic treatment of IH-exposed rats with ALLM rescued HIF-2α degradation and restored SOD2 activity, thereby preventing oxidative stress and hypertension. These observations demonstrate that, unlike continuous hypoxia, IH leads to down-regulation of HIF-2α via a calpain-dependent signaling pathway and results in oxidative stress as well as autonomic morbidities.

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Metadata

Authors
Nanduri, J., Wang, N., Yuan, G., Khan, S. A., Souvannakitti, D., Peng, Y.-J., Kumar, G. K., Garcia, J. A., & Prabhakar, N. R.
Venue
Proceedings of the National Academy of Sciences
Publisher
Proceedings of the National Academy of Sciences
Published
2009-01-27
Volume
106
Issue
4
Pages
1199-1204
ISSN
  • 0027-8424 (ISSN-L)
  • 1091-6490
DOI
10.1073/pnas.0811018106
OpenAlex
W2157849239
Cited by
186
References
9
FWCI
8.66
Type
journal article
Language
en
Open access
green

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CoChat. (2026). Citation check: Intermittent hypoxia degrades HIF-2α via calpains resulting in oxidative stress: Implications for recurrent apnea-induced morbidities. https://app.cochat.ai/papers/10.1073/pnas.0811018106
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Nanduri, J., Wang, N., Yuan, G., Khan, S. A., Souvannakitti, D., Peng, Y.-J., Kumar, G. K., Garcia, J. A., & Prabhakar, N. R. (2009). Intermittent hypoxia degrades HIF-2α via calpains resulting in oxidative stress: Implications for recurrent apnea-induced morbidities. Proceedings of the National Academy of Sciences. https://doi.org/10.1073/pnas.0811018106

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