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Overexpression of a...
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Li, TaoGothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi,Institute of Neuroscience and Physiology
(author)
Overexpression of apoptosis inducing factor aggravates hypoxic-ischemic brain injury in neonatal mice
- Article/chapterEnglish2020
Publisher, publication year, extent ...
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2020-01-30
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Springer Science and Business Media LLC,2020
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LIBRIS-ID:oai:gup.ub.gu.se/291555
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https://gup.ub.gu.se/publication/291555URI
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https://doi.org/10.1038/s41419-020-2280-zDOI
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http://kipublications.ki.se/Default.aspx?queryparsed=id:142901013URI
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Subject category:ref swepub-contenttype
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Subject category:art swepub-publicationtype
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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.
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Li, KenanGothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi,Institute of Neuroscience and Physiology
(author)
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Zhang, ShanGothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi,Institute of Neuroscience and Physiology
(author)
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Wang, Yafeng,1985Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi,Institute of Neuroscience and Physiology(Swepub:gu)xwayaf
(author)
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Xu, Yiran,1988Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi,Institute of Neuroscience and Physiology(Swepub:gu)xxuyiv
(author)
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Cronin, S. J. F.
(author)
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Sun, YanyanGothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi,Institute of Neuroscience and Physiology(Swepub:gu)xsunyg
(author)
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Zhang, YaodongGothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi,Institute of Neuroscience and Physiology
(author)
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Xie, CuicuiGothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi,Institute of Neuroscience and Physiology(Swepub:gu)xxiecu
(author)
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Rodriguez, Juan,1983Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi,Institute of Neuroscience and Physiology(Swepub:gu)xrodrj
(author)
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Zhou, KaiKarolinska Institutet,Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi,Institute of Neuroscience and Physiology(Swepub:gu)xzhoka
(author)
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Hagberg, Henrik,1955Gothenburg University,Göteborgs universitet,Institutionen för kliniska vetenskaper, Avdelningen för obstetrik och gynekologi,Institute of Clinical Sciences, Department of Obstetrics and Gynecology(Swepub:gu)xhaghe
(author)
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Mallard, Carina,1963Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi,Institute of Neuroscience and Physiology(Swepub:gu)xmallc
(author)
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Wang, Xiaoyang,1965Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi,Institute of Neuroscience and Physiology(Swepub:gu)xwanxi
(author)
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Penninger, J. M.
(author)
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Kroemer, G.
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Blomgren, K.Karolinska Institutet
(author)
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Zhu, Changlian,1964Karolinska Institutet,Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi,Institute of Neuroscience and Physiology(Swepub:gu)xzhuch
(author)
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Göteborgs universitetInstitutionen för neurovetenskap och fysiologi
(creator_code:org_t)
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In:Cell death & disease: Springer Science and Business Media LLC11:12041-4889
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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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Sun, Yanyan
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Zhang, Yaodong
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Xie, Cuicui
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Zhou, Kai
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Mallard, Carina, ...
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Penninger, J. M.
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Blomgren, K.
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