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Astrocytes produce nitric oxide via nitrite reduction in mitochondria to regulate cerebral blood flow during brain hypoxia

Research output: Contribution to Journal/Magazine › Journal article › peer-review

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Astrocytes produce nitric oxide via nitrite reduction in mitochondria to regulate cerebral blood flow during brain hypoxia. / Christie, Isabel N; Theparambil, Shefeeq M; Braga, Alice et al.
In: Cell Reports, Vol. 42, No. 12, 113514, 26.12.2023.

Research output: Contribution to Journal/Magazine › Journal article › peer-review

Harvard

Christie, IN, Theparambil, SM, Braga, A, Doronin, M, Hosford, PS, Brazhe, A, Mascarenhas, A, Nizari, S, Hadjihambi, A, Wells, JA, Hobbs, A, Semyanov, A, Abramov, AY, Angelova, PR & Gourine, AV 2023, 'Astrocytes produce nitric oxide via nitrite reduction in mitochondria to regulate cerebral blood flow during brain hypoxia', Cell Reports, vol. 42, no. 12, 113514. https://doi.org/10.1016/j.celrep.2023.113514

APA

Christie, I. N., Theparambil, S. M., Braga, A., Doronin, M., Hosford, P. S., Brazhe, A., Mascarenhas, A., Nizari, S., Hadjihambi, A., Wells, J. A., Hobbs, A., Semyanov, A., Abramov, A. Y., Angelova, P. R., & Gourine, A. V. (2023). Astrocytes produce nitric oxide via nitrite reduction in mitochondria to regulate cerebral blood flow during brain hypoxia. Cell Reports, 42(12), Article 113514. https://doi.org/10.1016/j.celrep.2023.113514

Vancouver

Christie IN, Theparambil SM, Braga A, Doronin M, Hosford PS, Brazhe A et al. Astrocytes produce nitric oxide via nitrite reduction in mitochondria to regulate cerebral blood flow during brain hypoxia. Cell Reports. 2023 Dec 26;42(12):113514. Epub 2023 Nov 30. doi: 10.1016/j.celrep.2023.113514

Author

Christie, Isabel N ; Theparambil, Shefeeq M ; Braga, Alice et al. / Astrocytes produce nitric oxide via nitrite reduction in mitochondria to regulate cerebral blood flow during brain hypoxia. In: Cell Reports. 2023 ; Vol. 42, No. 12.

Bibtex

@article{5c0afa3f82f44e84a836f14181062026,
title = "Astrocytes produce nitric oxide via nitrite reduction in mitochondria to regulate cerebral blood flow during brain hypoxia",
abstract = "During hypoxia, increases in cerebral blood flow maintain brain oxygen delivery. Here, we describe a mechanism of brain oxygen sensing that mediates the dilation of intraparenchymal cerebral blood vessels in response to reductions in oxygen supply. In vitro and in vivo experiments conducted in rodent models show that during hypoxia, cortical astrocytes produce the potent vasodilator nitric oxide (NO) via nitrite reduction in mitochondria. Inhibition of mitochondrial respiration mimics, but also occludes, the effect of hypoxia on NO production in astrocytes. Astrocytes display high expression of the molybdenum-cofactor-containing mitochondrial enzyme sulfite oxidase, which can catalyze nitrite reduction in hypoxia. Replacement of molybdenum with tungsten or knockdown of sulfite oxidase expression in astrocytes blocks hypoxia-induced NO production by these glial cells and reduces the cerebrovascular response to hypoxia. These data identify astrocyte mitochondria as brain oxygen sensors that regulate cerebral blood flow during hypoxia via release of nitric oxide.",
keywords = "Humans, Nitrites/metabolism, Astrocytes/metabolism, Nitric Oxide/metabolism, Molybdenum/metabolism, Hypoxia/metabolism, Oxygen/metabolism, Mitochondria/metabolism, Hypoxia, Brain/metabolism, Oxidoreductases Acting on Sulfur Group Donors/metabolism, Cerebrovascular Circulation",
author = "Christie, {Isabel N} and Theparambil, {Shefeeq M} and Alice Braga and Maxim Doronin and Hosford, {Patrick S} and Alexey Brazhe and Alexander Mascarenhas and Shereen Nizari and Anna Hadjihambi and Wells, {Jack A} and Adrian Hobbs and Alexey Semyanov and Abramov, {Andrey Y} and Angelova, {Plamena R} and Gourine, {Alexander V}",
year = "2023",
month = dec,
day = "26",
doi = "10.1016/j.celrep.2023.113514",
language = "English",
volume = "42",
journal = "Cell Reports",
issn = "2211-1247",
publisher = "Cell Press",
number = "12",

}

RIS

TY - JOUR

T1 - Astrocytes produce nitric oxide via nitrite reduction in mitochondria to regulate cerebral blood flow during brain hypoxia

AU - Christie, Isabel N

AU - Theparambil, Shefeeq M

AU - Braga, Alice

AU - Doronin, Maxim

AU - Hosford, Patrick S

AU - Brazhe, Alexey

AU - Mascarenhas, Alexander

AU - Nizari, Shereen

AU - Hadjihambi, Anna

AU - Wells, Jack A

AU - Hobbs, Adrian

AU - Semyanov, Alexey

AU - Abramov, Andrey Y

AU - Angelova, Plamena R

AU - Gourine, Alexander V

PY - 2023/12/26

Y1 - 2023/12/26

N2 - During hypoxia, increases in cerebral blood flow maintain brain oxygen delivery. Here, we describe a mechanism of brain oxygen sensing that mediates the dilation of intraparenchymal cerebral blood vessels in response to reductions in oxygen supply. In vitro and in vivo experiments conducted in rodent models show that during hypoxia, cortical astrocytes produce the potent vasodilator nitric oxide (NO) via nitrite reduction in mitochondria. Inhibition of mitochondrial respiration mimics, but also occludes, the effect of hypoxia on NO production in astrocytes. Astrocytes display high expression of the molybdenum-cofactor-containing mitochondrial enzyme sulfite oxidase, which can catalyze nitrite reduction in hypoxia. Replacement of molybdenum with tungsten or knockdown of sulfite oxidase expression in astrocytes blocks hypoxia-induced NO production by these glial cells and reduces the cerebrovascular response to hypoxia. These data identify astrocyte mitochondria as brain oxygen sensors that regulate cerebral blood flow during hypoxia via release of nitric oxide.

AB - During hypoxia, increases in cerebral blood flow maintain brain oxygen delivery. Here, we describe a mechanism of brain oxygen sensing that mediates the dilation of intraparenchymal cerebral blood vessels in response to reductions in oxygen supply. In vitro and in vivo experiments conducted in rodent models show that during hypoxia, cortical astrocytes produce the potent vasodilator nitric oxide (NO) via nitrite reduction in mitochondria. Inhibition of mitochondrial respiration mimics, but also occludes, the effect of hypoxia on NO production in astrocytes. Astrocytes display high expression of the molybdenum-cofactor-containing mitochondrial enzyme sulfite oxidase, which can catalyze nitrite reduction in hypoxia. Replacement of molybdenum with tungsten or knockdown of sulfite oxidase expression in astrocytes blocks hypoxia-induced NO production by these glial cells and reduces the cerebrovascular response to hypoxia. These data identify astrocyte mitochondria as brain oxygen sensors that regulate cerebral blood flow during hypoxia via release of nitric oxide.

KW - Humans

KW - Nitrites/metabolism

KW - Astrocytes/metabolism

KW - Nitric Oxide/metabolism

KW - Molybdenum/metabolism

KW - Hypoxia/metabolism

KW - Oxygen/metabolism

KW - Mitochondria/metabolism

KW - Hypoxia, Brain/metabolism

KW - Oxidoreductases Acting on Sulfur Group Donors/metabolism

KW - Cerebrovascular Circulation

U2 - 10.1016/j.celrep.2023.113514

DO - 10.1016/j.celrep.2023.113514

M3 - Journal article

C2 - 38041814

VL - 42

JO - Cell Reports

JF - Cell Reports

SN - 2211-1247

IS - 12

M1 - 113514

ER -