Overexpression of apoptosis inducing factor aggravates hypoxic-ischemic brain injury in neonatal mice - Sorbonne Université
Journal Articles Cell Death and Disease Year : 2020

Overexpression of apoptosis inducing factor aggravates hypoxic-ischemic brain injury in neonatal mice

Abstract

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.
Fichier principal
Vignette du fichier
s41419-020-2280-z.pdf (4.24 Mo) Télécharger le fichier
Origin Publication funded by an institution
Loading...

Dates and versions

hal-02489415 , version 1 (24-02-2020)

Identifiers

Cite

Tao Li, Kenan Li, Shan Zhang, Yafeng Wang, Yiran Xu, et al.. Overexpression of apoptosis inducing factor aggravates hypoxic-ischemic brain injury in neonatal mice. Cell Death and Disease, 2020, 11 (1), pp.77. ⟨10.1038/s41419-020-2280-z⟩. ⟨hal-02489415⟩
50 View
64 Download

Altmetric

Share

More