Characterization of gene expression associated with the adaptation of the nematode C. elegans to hypoxia and reoxygenation stress reveals an unexpected function of the neuroglobin GLB-5 in innate immunity

Binyamin Zuckerman‎; Zohar Abergel; Veronica Zelmanovich; Leonor Romero; Rachel Abergel; Leonid Livshits; Yoav Smith; Einav Gross

doi:10.1016/j.freeradbiomed.2017.05.007

Characterization of gene expression associated with the adaptation of the nematode C. elegans to hypoxia and reoxygenation stress reveals an unexpected function of the neuroglobin GLB-5 in innate immunity

Binyamin Zuckerman‎, Zohar Abergel, Veronica Zelmanovich, Leonor Romero, Rachel Abergel, Leonid Livshits, Yoav Smith, Einav Gross^*

^*Corresponding author for this work

Department of Biochemistry and Molecular Biology

Research output: Contribution to journal › Article › peer-review

11 Scopus citations

Abstract

Oxygen (O₂) is a double-edged sword to cells, for while it is vital for energy production in all aerobic animals and insufficient O₂ (hypoxia) can lead to cell death, the reoxygenation of hypoxic tissues may trigger the generation of reactive oxygen species (ROS) that can destroy any biological molecule. Indeed, both hypoxia and hypoxia-reoxygenation (H/R) stress are harmful, and may play a critical role in the pathophysiology of many human diseases, such as myocardial ischemia and stroke. Therefore, understanding how animals adapt to hypoxia and H/R stress is critical for developing better treatments for these diseases. Previous studies showed that the neuroglobin GLB-5(Haw) is essential for the fast recovery of the nematode Caenorhabditis elegans (C. elegans) from H/R stress. Here, we characterize the changes in neuronal gene expression during the adaptation of worms to hypoxia and recovery from H/R stress. Our analysis shows that innate immunity genes are differentially expressed during both adaptation to hypoxia and recovery from H/R stress. Moreover, we reveal that the prolyl hydroxylase EGL-9, a known regulator of both adaptation to hypoxia and the innate immune response, inhibits the fast recovery from H/R stress through its activity in the O₂-sensing neurons AQR, PQR, and URX. Finally, we show that GLB-5(Haw) acts in AQR, PQR, and URX to increase the tolerance of worms to Pseudomonas aeruginosa pathogenesis. Together, our studies suggest that innate immunity and recovery from H/R stress are regulated by overlapping signaling pathways.

Original language	American English
Pages (from-to)	858-873
Number of pages	16
Journal	Free Radical Biology and Medicine
Volume	108
DOIs	https://doi.org/10.1016/j.freeradbiomed.2017.05.007
State	Published - 1 Jul 2017

Bibliographical note

Funding Information:
We thank Gillian Kay for critical reading of the manuscript and the Gross laboratory members for comments and advice. Some strains were provided by the CGC, which is funded by National Institutes of Health Office of Research Infrastructure Programs (P40 OD010440), the C. elegans Knockout Consortium, and the National BioResource Project (Japan). The research leading to these results has received funding from the European Research Council under the European Union's Seventh Framework Programme (FP/2007–2013)/ERC Grant Agreement no. 281844. (B.Z, Z.A, V.Z, L. R, R. A, and E.G).

Publisher Copyright:
© 2017 Elsevier Inc.

Keywords

C. elegans
EGL-9
GLB-5
HIF-1
Hypoxia
Hypoxia-reoxygenation stress
Innate immunity
Neuroglobin
npr-1

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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Zuckerman‎, B., Abergel, Z., Zelmanovich, V., Romero, L., Abergel, R., Livshits, L., Smith, Y., & Gross, E. (2017). Characterization of gene expression associated with the adaptation of the nematode C. elegans to hypoxia and reoxygenation stress reveals an unexpected function of the neuroglobin GLB-5 in innate immunity. Free Radical Biology and Medicine, 108, 858-873. https://doi.org/10.1016/j.freeradbiomed.2017.05.007

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title = "Characterization of gene expression associated with the adaptation of the nematode C. elegans to hypoxia and reoxygenation stress reveals an unexpected function of the neuroglobin GLB-5 in innate immunity",

abstract = "Oxygen (O2) is a double-edged sword to cells, for while it is vital for energy production in all aerobic animals and insufficient O2 (hypoxia) can lead to cell death, the reoxygenation of hypoxic tissues may trigger the generation of reactive oxygen species (ROS) that can destroy any biological molecule. Indeed, both hypoxia and hypoxia-reoxygenation (H/R) stress are harmful, and may play a critical role in the pathophysiology of many human diseases, such as myocardial ischemia and stroke. Therefore, understanding how animals adapt to hypoxia and H/R stress is critical for developing better treatments for these diseases. Previous studies showed that the neuroglobin GLB-5(Haw) is essential for the fast recovery of the nematode Caenorhabditis elegans (C. elegans) from H/R stress. Here, we characterize the changes in neuronal gene expression during the adaptation of worms to hypoxia and recovery from H/R stress. Our analysis shows that innate immunity genes are differentially expressed during both adaptation to hypoxia and recovery from H/R stress. Moreover, we reveal that the prolyl hydroxylase EGL-9, a known regulator of both adaptation to hypoxia and the innate immune response, inhibits the fast recovery from H/R stress through its activity in the O2-sensing neurons AQR, PQR, and URX. Finally, we show that GLB-5(Haw) acts in AQR, PQR, and URX to increase the tolerance of worms to Pseudomonas aeruginosa pathogenesis. Together, our studies suggest that innate immunity and recovery from H/R stress are regulated by overlapping signaling pathways.",

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author = "Binyamin Zuckerman‎ and Zohar Abergel and Veronica Zelmanovich and Leonor Romero and Rachel Abergel and Leonid Livshits and Yoav Smith and Einav Gross",

note = "Funding Information: We thank Gillian Kay for critical reading of the manuscript and the Gross laboratory members for comments and advice. Some strains were provided by the CGC, which is funded by National Institutes of Health Office of Research Infrastructure Programs (P40 OD010440), the C. elegans Knockout Consortium, and the National BioResource Project (Japan). The research leading to these results has received funding from the European Research Council under the European Union's Seventh Framework Programme (FP/2007–2013)/ERC Grant Agreement no. 281844. (B.Z, Z.A, V.Z, L. R, R. A, and E.G). Publisher Copyright: {\textcopyright} 2017 Elsevier Inc.",

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Zuckerman‎, B, Abergel, Z, Zelmanovich, V, Romero, L, Abergel, R, Livshits, L, Smith, Y & Gross, E 2017, 'Characterization of gene expression associated with the adaptation of the nematode C. elegans to hypoxia and reoxygenation stress reveals an unexpected function of the neuroglobin GLB-5 in innate immunity', Free Radical Biology and Medicine, vol. 108, pp. 858-873. https://doi.org/10.1016/j.freeradbiomed.2017.05.007

Characterization of gene expression associated with the adaptation of the nematode C. elegans to hypoxia and reoxygenation stress reveals an unexpected function of the neuroglobin GLB-5 in innate immunity. / Zuckerman‎, Binyamin; Abergel, Zohar; Zelmanovich, Veronica et al.
In: Free Radical Biology and Medicine, Vol. 108, 01.07.2017, p. 858-873.

Research output: Contribution to journal › Article › peer-review

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AU - Zuckerman‎, Binyamin

AU - Abergel, Zohar

AU - Zelmanovich, Veronica

AU - Romero, Leonor

AU - Abergel, Rachel

AU - Livshits, Leonid

AU - Smith, Yoav

AU - Gross, Einav

N1 - Funding Information: We thank Gillian Kay for critical reading of the manuscript and the Gross laboratory members for comments and advice. Some strains were provided by the CGC, which is funded by National Institutes of Health Office of Research Infrastructure Programs (P40 OD010440), the C. elegans Knockout Consortium, and the National BioResource Project (Japan). The research leading to these results has received funding from the European Research Council under the European Union's Seventh Framework Programme (FP/2007–2013)/ERC Grant Agreement no. 281844. (B.Z, Z.A, V.Z, L. R, R. A, and E.G). Publisher Copyright: © 2017 Elsevier Inc.

PY - 2017/7/1

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N2 - Oxygen (O2) is a double-edged sword to cells, for while it is vital for energy production in all aerobic animals and insufficient O2 (hypoxia) can lead to cell death, the reoxygenation of hypoxic tissues may trigger the generation of reactive oxygen species (ROS) that can destroy any biological molecule. Indeed, both hypoxia and hypoxia-reoxygenation (H/R) stress are harmful, and may play a critical role in the pathophysiology of many human diseases, such as myocardial ischemia and stroke. Therefore, understanding how animals adapt to hypoxia and H/R stress is critical for developing better treatments for these diseases. Previous studies showed that the neuroglobin GLB-5(Haw) is essential for the fast recovery of the nematode Caenorhabditis elegans (C. elegans) from H/R stress. Here, we characterize the changes in neuronal gene expression during the adaptation of worms to hypoxia and recovery from H/R stress. Our analysis shows that innate immunity genes are differentially expressed during both adaptation to hypoxia and recovery from H/R stress. Moreover, we reveal that the prolyl hydroxylase EGL-9, a known regulator of both adaptation to hypoxia and the innate immune response, inhibits the fast recovery from H/R stress through its activity in the O2-sensing neurons AQR, PQR, and URX. Finally, we show that GLB-5(Haw) acts in AQR, PQR, and URX to increase the tolerance of worms to Pseudomonas aeruginosa pathogenesis. Together, our studies suggest that innate immunity and recovery from H/R stress are regulated by overlapping signaling pathways.

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KW - C. elegans

KW - EGL-9

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KW - HIF-1

KW - Hypoxia

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KW - Neuroglobin

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SN - 0891-5849

VL - 108

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JO - Free Radical Biology and Medicine

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Zuckerman‎ B, Abergel Z, Zelmanovich V, Romero L, Abergel R, Livshits L et al. Characterization of gene expression associated with the adaptation of the nematode C. elegans to hypoxia and reoxygenation stress reveals an unexpected function of the neuroglobin GLB-5 in innate immunity. Free Radical Biology and Medicine. 2017 Jul 1;108:858-873. doi: 10.1016/j.freeradbiomed.2017.05.007

Characterization of gene expression associated with the adaptation of the nematode C. elegans to hypoxia and reoxygenation stress reveals an unexpected function of the neuroglobin GLB-5 in innate immunity

Abstract

Bibliographical note

Keywords

UN SDGs

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