Notch Signaling and Cross-Talk in Hypoxia: A Candidate Pathway for High-Altitude Adaptation
Hypoxia triggers complex inter- and intracellular signals that regulate tissue oxygen (O<sub>2</sub>) homeostasis, adjusting convective O<sub>2</sub> delivery and utilization (i.e., metabolism). Human populations have been exposed to high-altitude hypoxia for thousands of yea...
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| Format: | Article |
| Language: | English |
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MDPI AG
2022-03-01
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| Series: | Life |
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| Online Access: | https://www.mdpi.com/2075-1729/12/3/437 |
| _version_ | 1827628497894375424 |
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| author | Katie A. O’Brien Andrew J. Murray Tatum S. Simonson |
| author_facet | Katie A. O’Brien Andrew J. Murray Tatum S. Simonson |
| author_sort | Katie A. O’Brien |
| collection | DOAJ |
| description | Hypoxia triggers complex inter- and intracellular signals that regulate tissue oxygen (O<sub>2</sub>) homeostasis, adjusting convective O<sub>2</sub> delivery and utilization (i.e., metabolism). Human populations have been exposed to high-altitude hypoxia for thousands of years and, in doing so, have undergone natural selection of multiple gene regions supporting adaptive traits. Some of the strongest selection signals identified in highland populations emanate from hypoxia-inducible factor (HIF) pathway genes. The HIF pathway is a master regulator of the cellular hypoxic response, but it is not the only regulatory pathway under positive selection. For instance, regions linked to the highly conserved Notch signaling pathway are also top targets, and this pathway is likely to play essential roles that confer hypoxia tolerance. Here, we explored the importance of the Notch pathway in mediating the cellular hypoxic response. We assessed transcriptional regulation of the Notch pathway, including close cross-talk with HIF signaling, and its involvement in the mediation of angiogenesis, cellular metabolism, inflammation, and oxidative stress, relating these functions to generational hypoxia adaptation. |
| first_indexed | 2024-03-09T13:33:51Z |
| format | Article |
| id | doaj.art-a79f616d26214601b6b24978ece3804a |
| institution | Directory Open Access Journal |
| issn | 2075-1729 |
| language | English |
| last_indexed | 2024-03-09T13:33:51Z |
| publishDate | 2022-03-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Life |
| spelling | doaj.art-a79f616d26214601b6b24978ece3804a2023-11-30T21:14:42ZengMDPI AGLife2075-17292022-03-0112343710.3390/life12030437Notch Signaling and Cross-Talk in Hypoxia: A Candidate Pathway for High-Altitude AdaptationKatie A. O’Brien0Andrew J. Murray1Tatum S. Simonson2Department of Physiology, Development and Neuroscience, University of Cambridge, Downing Street, Cambridge CB2 3EG, UKDepartment of Physiology, Development and Neuroscience, University of Cambridge, Downing Street, Cambridge CB2 3EG, UKDivision of Pulmonary, Critical Care and Sleep Medicine, University of California San Diego School of Medicine, La Jolla, CA 92093, USAHypoxia triggers complex inter- and intracellular signals that regulate tissue oxygen (O<sub>2</sub>) homeostasis, adjusting convective O<sub>2</sub> delivery and utilization (i.e., metabolism). Human populations have been exposed to high-altitude hypoxia for thousands of years and, in doing so, have undergone natural selection of multiple gene regions supporting adaptive traits. Some of the strongest selection signals identified in highland populations emanate from hypoxia-inducible factor (HIF) pathway genes. The HIF pathway is a master regulator of the cellular hypoxic response, but it is not the only regulatory pathway under positive selection. For instance, regions linked to the highly conserved Notch signaling pathway are also top targets, and this pathway is likely to play essential roles that confer hypoxia tolerance. Here, we explored the importance of the Notch pathway in mediating the cellular hypoxic response. We assessed transcriptional regulation of the Notch pathway, including close cross-talk with HIF signaling, and its involvement in the mediation of angiogenesis, cellular metabolism, inflammation, and oxidative stress, relating these functions to generational hypoxia adaptation.https://www.mdpi.com/2075-1729/12/3/437hypobaric hypoxiaadaptationNotch signalinghypoxia-inducible factor |
| spellingShingle | Katie A. O’Brien Andrew J. Murray Tatum S. Simonson Notch Signaling and Cross-Talk in Hypoxia: A Candidate Pathway for High-Altitude Adaptation Life hypobaric hypoxia adaptation Notch signaling hypoxia-inducible factor |
| title | Notch Signaling and Cross-Talk in Hypoxia: A Candidate Pathway for High-Altitude Adaptation |
| title_full | Notch Signaling and Cross-Talk in Hypoxia: A Candidate Pathway for High-Altitude Adaptation |
| title_fullStr | Notch Signaling and Cross-Talk in Hypoxia: A Candidate Pathway for High-Altitude Adaptation |
| title_full_unstemmed | Notch Signaling and Cross-Talk in Hypoxia: A Candidate Pathway for High-Altitude Adaptation |
| title_short | Notch Signaling and Cross-Talk in Hypoxia: A Candidate Pathway for High-Altitude Adaptation |
| title_sort | notch signaling and cross talk in hypoxia a candidate pathway for high altitude adaptation |
| topic | hypobaric hypoxia adaptation Notch signaling hypoxia-inducible factor |
| url | https://www.mdpi.com/2075-1729/12/3/437 |
| work_keys_str_mv | AT katieaobrien notchsignalingandcrosstalkinhypoxiaacandidatepathwayforhighaltitudeadaptation AT andrewjmurray notchsignalingandcrosstalkinhypoxiaacandidatepathwayforhighaltitudeadaptation AT tatumssimonson notchsignalingandcrosstalkinhypoxiaacandidatepathwayforhighaltitudeadaptation |