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Overexpression of a...
Overexpression of apoptosis inducing factor aggravates hypoxic-ischemic brain injury in neonatal mice
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- Li, Tao (author)
- Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi,Institute of Neuroscience and Physiology
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- Li, Kenan (author)
- Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi,Institute of Neuroscience and Physiology
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- Zhang, Shan (author)
- Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi,Institute of Neuroscience and Physiology
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- Wang, Yafeng, 1985 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi,Institute of Neuroscience and Physiology
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- Xu, Yiran, 1988 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi,Institute of Neuroscience and Physiology
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Cronin, S. J. F. (author)
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- Sun, Yanyan (author)
- Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi,Institute of Neuroscience and Physiology
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- Zhang, Yaodong (author)
- Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi,Institute of Neuroscience and Physiology
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- Xie, Cuicui (author)
- Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi,Institute of Neuroscience and Physiology
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- Rodriguez, Juan, 1983 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi,Institute of Neuroscience and Physiology
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- Zhou, Kai (author)
- Karolinska Institutet,Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi,Institute of Neuroscience and Physiology
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- Hagberg, Henrik, 1955 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för kliniska vetenskaper, Avdelningen för obstetrik och gynekologi,Institute of Clinical Sciences, Department of Obstetrics and Gynecology
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- Mallard, Carina, 1963 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi,Institute of Neuroscience and Physiology
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- Wang, Xiaoyang, 1965 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi,Institute of Neuroscience and Physiology
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Penninger, J. M. (author)
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Kroemer, G. (author)
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- Blomgren, K. (author)
- Karolinska Institutet
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- Zhu, Changlian, 1964 (author)
- Karolinska Institutet,Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi,Institute of Neuroscience and Physiology
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(creator_code:org_t)
- 2020-01-30
- 2020
- English.
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In: Cell death & disease. - : Springer Science and Business Media LLC. - 2041-4889. ; 11:1
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https://www.nature.c...
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https://gup.ub.gu.se...
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Abstract
Subject headings
Close
- Apoptosis inducing factor (AIF) has been shown to be a major contributor to neuron loss in the immature brain after hypoxia-ischemia (HI). Indeed, mice bearing a hypomorphic mutation causing reduced AIF expression are protected against neonatal HI. To further investigate the possible molecular mechanisms of this neuroprotection, we generated an AIF knock-in mouse by introduction of a latent transgene coding for flagged AIF protein into the Rosa26 locus, followed by its conditional activation by a ubiquitously expressed Cre recombinase. Such AIF transgenic mice overexpress the pro-apoptotic splice variant of AIF (AIF1) at both the mRNA (5.9 times higher) and protein level (2.4 times higher), but not the brain-specific AIF splice-isoform (AIF2). Excessive AIF did not have any apparent effects on the phenotype or physiological functions of the mice. However, brain injury (both gray and white matter) after neonatal HI was exacerbated in mice overexpressing AIF, coupled to enhanced translocation of mitochondrial AIF to the nucleus as well as enhanced caspase-3 activation in some brain regions, as indicated by immunohistochemistry. Altogether, these findings corroborate earlier studies demonstrating that AIF plays a causal role in neonatal HI brain injury.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine (hsv//eng)
Keyword
- neuronal cell-death
- poly(adp-ribose) polymerase
- therapeutic
- hypothermia
- mitochondrial dynamics
- factor leads
- aif
- encephalopathy
- neuroprotection
- hippocampus
- inhibition
- Cell Biology
Publication and Content Type
- ref (subject category)
- art (subject category)
Find in a library
To the university's database
- By the author/editor
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Li, Tao
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Li, Kenan
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Zhang, Shan
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Wang, Yafeng, 19 ...
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Xu, Yiran, 1988
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Cronin, S. J. F.
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show more...
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Sun, Yanyan
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Zhang, Yaodong
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Xie, Cuicui
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Rodriguez, Juan, ...
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Zhou, Kai
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Hagberg, Henrik, ...
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Mallard, Carina, ...
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Wang, Xiaoyang, ...
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Penninger, J. M.
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Kroemer, G.
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Blomgren, K.
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Zhu, Changlian, ...
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show less...
- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Clinical Medicin ...
- Articles in the publication
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Cell death & dis ...
- By the university
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University of Gothenburg
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Karolinska Institutet