NADPH Oxidase 4 (Nox4) Suppresses Mitochondrial Biogenesis and Bioenergetics in Lung Fibroblasts via a Nuclear Factor Erythroid-derived 2-like 2 (Nrf2)-dependent Pathway
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Bernard, Karen
[1
]
Logsdon, Naomi J.
论文数: 0引用数: 0
h-index: 0
机构:
Univ Alabama Birmingham, Div Pulm Allergy & Crit Care Med, Birmingham, AL USAUniv Alabama Birmingham, Div Pulm Allergy & Crit Care Med, Birmingham, AL USA
Logsdon, Naomi J.
[1
]
Miguel, Veronica
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UAM, CSIC, Ctr Biol Mol Severo Ochoa, Madrid 28049, SpainUniv Alabama Birmingham, Div Pulm Allergy & Crit Care Med, Birmingham, AL USA
Miguel, Veronica
[5
]
Benavides, Gloria A.
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Univ Alabama Birmingham, Dept Pathol, Birmingham, AL 35294 USA
Univ Alabama Birmingham, Ctr Free Rad Biol & Med, Birmingham, AL USAUniv Alabama Birmingham, Div Pulm Allergy & Crit Care Med, Birmingham, AL USA
Benavides, Gloria A.
[2
,3
]
Zhang, Jianhua
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Univ Alabama Birmingham, Dept Pathol, Birmingham, AL 35294 USA
Univ Alabama Birmingham, Ctr Free Rad Biol & Med, Birmingham, AL USAUniv Alabama Birmingham, Div Pulm Allergy & Crit Care Med, Birmingham, AL USA
Zhang, Jianhua
[2
,3
]
Carter, A. Brent
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Univ Alabama Birmingham, Div Pulm Allergy & Crit Care Med, Birmingham, AL USA
Birmingham Vet Adm Med Ctr, Birmingham, AL 35294 USAUniv Alabama Birmingham, Div Pulm Allergy & Crit Care Med, Birmingham, AL USA
Carter, A. Brent
[1
,4
]
Darley-Usmar, Victor M.
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Univ Alabama Birmingham, Dept Pathol, Birmingham, AL 35294 USA
Univ Alabama Birmingham, Ctr Free Rad Biol & Med, Birmingham, AL USAUniv Alabama Birmingham, Div Pulm Allergy & Crit Care Med, Birmingham, AL USA
Darley-Usmar, Victor M.
[2
,3
]
Thannickal, Victor J.
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Univ Alabama Birmingham, Div Pulm Allergy & Crit Care Med, Birmingham, AL USAUniv Alabama Birmingham, Div Pulm Allergy & Crit Care Med, Birmingham, AL USA
Thannickal, Victor J.
[1
]
机构:
[1] Univ Alabama Birmingham, Div Pulm Allergy & Crit Care Med, Birmingham, AL USA
[2] Univ Alabama Birmingham, Dept Pathol, Birmingham, AL 35294 USA
[3] Univ Alabama Birmingham, Ctr Free Rad Biol & Med, Birmingham, AL USA
[4] Birmingham Vet Adm Med Ctr, Birmingham, AL 35294 USA
Mitochondrial bioenergetics are critical for cellular homeostasis and stress responses. The reactive oxygen species-generating enzyme, NADPH oxidase 4 (Nox4), regulates a number of physiological and pathological processes, including cellular differentiation, host defense, and tissue fibrosis. In this study we explored the role of constitutive Nox4 activity in regulating mitochondrial function. An increase in mitochondrial oxygen consumption and reserve capacity was observed in murine and human lung fibroblasts with genetic deficiency (or silencing) of Nox4. Inhibition of Nox4 expression/activity by genetic or pharmacological approaches resulted in stimulation of mitochondrial biogenesis, as evidenced by elevated mitochondrial-to-nuclear DNA ratio and increased expression of the mitochondrial markers transcription factor A (TFAM), citrate synthase, voltage-dependent anion channel (VDAC), and cytochrome c oxidase subunit 4 (COX IV). Induction of mitochondrial biogenesis was dependent on TFAM up-regulation but was independent of the activation of the peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1 alpha). The enhancement of mitochondrial bioenergetics as well as the increase in mitochondrial proteins in Nox4-deficient lung fibroblasts is inhibited by silencing of nuclear factor erythroid-derived 2-like 2 (Nrf2), supporting a key role for Nrf2 in control of mitochondrial biogenesis. Together, these results indicate a critical role for both Nox4 and Nrf2 in counter-regulation of mitochondrial biogenesis and metabolism.
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页码:3029 / 3038
页数:10
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[1]
Barbour Jayne Alexandra, 2014, Int J Cell Biol, V2014, P156020, DOI 10.1155/2014/156020
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Univ Alabama Birmingham, Div Pulm Allergy & Crit Care Med, Birmingham, AL 35294 USAUniv Alabama Birmingham, Div Pulm Allergy & Crit Care Med, Birmingham, AL 35294 USA
Logsdon, Naomi J.
;
Ravi, Saranya
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Univ Alabama Birmingham, Dept Pathol, Birmingham, AL 35294 USA
Univ Alabama Birmingham, Ctr Free Rad Biol & Med, Birmingham, AL 35294 USAUniv Alabama Birmingham, Div Pulm Allergy & Crit Care Med, Birmingham, AL 35294 USA
Ravi, Saranya
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Xie, Na
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Univ Alabama Birmingham, Div Pulm Allergy & Crit Care Med, Birmingham, AL 35294 USAUniv Alabama Birmingham, Div Pulm Allergy & Crit Care Med, Birmingham, AL 35294 USA
Xie, Na
;
Persons, Benjamin P.
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Univ Alabama Birmingham, Div Pulm Allergy & Crit Care Med, Birmingham, AL 35294 USAUniv Alabama Birmingham, Div Pulm Allergy & Crit Care Med, Birmingham, AL 35294 USA
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Rangarajan, Sunad
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Univ Alabama Birmingham, Div Pulm Allergy & Crit Care Med, Birmingham, AL 35294 USAUniv Alabama Birmingham, Div Pulm Allergy & Crit Care Med, Birmingham, AL 35294 USA
Rangarajan, Sunad
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Zmijewski, Jaroslaw W.
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Univ Alabama Birmingham, Div Pulm Allergy & Crit Care Med, Birmingham, AL 35294 USAUniv Alabama Birmingham, Div Pulm Allergy & Crit Care Med, Birmingham, AL 35294 USA
Zmijewski, Jaroslaw W.
;
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Mitra, Kasturi
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Liu, Gang
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Univ Alabama Birmingham, Div Pulm Allergy & Crit Care Med, Birmingham, AL 35294 USAUniv Alabama Birmingham, Div Pulm Allergy & Crit Care Med, Birmingham, AL 35294 USA
Liu, Gang
;
Darley-Usmar, Victor M.
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Univ Alabama Birmingham, Dept Pathol, Birmingham, AL 35294 USA
Univ Alabama Birmingham, Ctr Free Rad Biol & Med, Birmingham, AL 35294 USAUniv Alabama Birmingham, Div Pulm Allergy & Crit Care Med, Birmingham, AL 35294 USA
Darley-Usmar, Victor M.
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Thannickal, Victor J.
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Univ Alabama Birmingham, Div Pulm Allergy & Crit Care Med, Birmingham, AL 35294 USAUniv Alabama Birmingham, Div Pulm Allergy & Crit Care Med, Birmingham, AL 35294 USA
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Univ Texas Hlth Sci Ctr San Antonio, Dept Med, San Antonio, TX 78229 USAUniv Texas Hlth Sci Ctr San Antonio, Dept Med, San Antonio, TX 78229 USA
Block, Karen
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Gorin, Yves
;
Abboud, Hanna E.
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Univ Texas Hlth Sci Ctr San Antonio, Dept Med, San Antonio, TX 78229 USA
S Texas Vet Hlth Care Syst, Audie Leon Murphy Mem Hosp Div, San Antonio, TX 78229 USAUniv Texas Hlth Sci Ctr San Antonio, Dept Med, San Antonio, TX 78229 USA
机构:
Univ Alabama Birmingham, Div Pulm Allergy & Crit Care Med, Birmingham, AL 35294 USAUniv Alabama Birmingham, Div Pulm Allergy & Crit Care Med, Birmingham, AL 35294 USA
Logsdon, Naomi J.
;
Ravi, Saranya
论文数: 0引用数: 0
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Univ Alabama Birmingham, Dept Pathol, Birmingham, AL 35294 USA
Univ Alabama Birmingham, Ctr Free Rad Biol & Med, Birmingham, AL 35294 USAUniv Alabama Birmingham, Div Pulm Allergy & Crit Care Med, Birmingham, AL 35294 USA
Ravi, Saranya
;
Xie, Na
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Univ Alabama Birmingham, Div Pulm Allergy & Crit Care Med, Birmingham, AL 35294 USAUniv Alabama Birmingham, Div Pulm Allergy & Crit Care Med, Birmingham, AL 35294 USA
Xie, Na
;
Persons, Benjamin P.
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Univ Alabama Birmingham, Div Pulm Allergy & Crit Care Med, Birmingham, AL 35294 USAUniv Alabama Birmingham, Div Pulm Allergy & Crit Care Med, Birmingham, AL 35294 USA
Persons, Benjamin P.
;
Rangarajan, Sunad
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Univ Alabama Birmingham, Div Pulm Allergy & Crit Care Med, Birmingham, AL 35294 USAUniv Alabama Birmingham, Div Pulm Allergy & Crit Care Med, Birmingham, AL 35294 USA
Rangarajan, Sunad
;
Zmijewski, Jaroslaw W.
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Univ Alabama Birmingham, Div Pulm Allergy & Crit Care Med, Birmingham, AL 35294 USAUniv Alabama Birmingham, Div Pulm Allergy & Crit Care Med, Birmingham, AL 35294 USA
Zmijewski, Jaroslaw W.
;
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Mitra, Kasturi
;
Liu, Gang
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Univ Alabama Birmingham, Div Pulm Allergy & Crit Care Med, Birmingham, AL 35294 USAUniv Alabama Birmingham, Div Pulm Allergy & Crit Care Med, Birmingham, AL 35294 USA
Liu, Gang
;
Darley-Usmar, Victor M.
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Univ Alabama Birmingham, Dept Pathol, Birmingham, AL 35294 USA
Univ Alabama Birmingham, Ctr Free Rad Biol & Med, Birmingham, AL 35294 USAUniv Alabama Birmingham, Div Pulm Allergy & Crit Care Med, Birmingham, AL 35294 USA
Darley-Usmar, Victor M.
;
Thannickal, Victor J.
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Univ Alabama Birmingham, Div Pulm Allergy & Crit Care Med, Birmingham, AL 35294 USAUniv Alabama Birmingham, Div Pulm Allergy & Crit Care Med, Birmingham, AL 35294 USA
机构:
Univ Texas Hlth Sci Ctr San Antonio, Dept Med, San Antonio, TX 78229 USAUniv Texas Hlth Sci Ctr San Antonio, Dept Med, San Antonio, TX 78229 USA
Block, Karen
;
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Gorin, Yves
;
Abboud, Hanna E.
论文数: 0引用数: 0
h-index: 0
机构:
Univ Texas Hlth Sci Ctr San Antonio, Dept Med, San Antonio, TX 78229 USA
S Texas Vet Hlth Care Syst, Audie Leon Murphy Mem Hosp Div, San Antonio, TX 78229 USAUniv Texas Hlth Sci Ctr San Antonio, Dept Med, San Antonio, TX 78229 USA