Downregulation of Iduna is associated with AIF nuclear translocation in neonatal brain after hypoxia–ischemia

Yang, Xiaoxia; Cheng, Jianhua; Gao, Yubo; Ding, Juan; Ni, Xinli

doi:10.1016/j.neuroscience.2017.01.010

Cited by 8 publications

(4 citation statements)

References 24 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This specific route of cell death that depends on PARP-1 and AIF is often referred to as Parthanatos (Figure 1 ) rather than apoptosis (Fatokun et al, 2014 ) and exhibits morphologic features of regulated necrosis rather than apoptosis (Vanden Berghe et al, 2014 ). The protein IDUNA has been discovered to inhibit this pathway in the adult brain (Andrabi et al, 2011 ) which seems to apply also to the immature brain (Yang et al, 2017 ). Taken together, these data suggest that BAX-dependent MOMP is a critical event in delayed brain injury in the immature brain because it leads to both activation of caspase-dependent and caspase-independent cell death.…”

Section: Apoptotic Cell Deathmentioning

confidence: 99%

Cell Death in the Developing Brain after Hypoxia-Ischemia

Thornton

Leaw

Mallard

et al. 2017

Front. Cell. Neurosci.

133

View full text Add to dashboard Cite

Perinatal insults such as hypoxia–ischemia induces secondary brain injury. In order to develop the next generation of neuroprotective therapies, we urgently need to understand the underlying molecular mechanisms leading to cell death. The cell death mechanisms have been shown to be quite different in the developing brain compared to that in the adult. The aim of this review is update on what cell death mechanisms that are operating particularly in the setting of the developing CNS. In response to mild stress stimuli a number of compensatory mechanisms will be activated, most often leading to cell survival. Moderate-to-severe insults trigger regulated cell death. Depending on several factors such as the metabolic situation, cell type, nature of the stress stimulus, and which intracellular organelle(s) are affected, the cell undergoes apoptosis (caspase activation) triggered by BAX dependent mitochondrial permeabilzation, necroptosis (mixed lineage kinase domain-like activation), necrosis (via opening of the mitochondrial permeability transition pore), autophagic cell death (autophagy/Na+, K+-ATPase), or parthanatos (poly(ADP-ribose) polymerase 1, apoptosis-inducing factor). Severe insults cause accidental cell death that cannot be modulated genetically or by pharmacologic means. However, accidental cell death leads to the release of factors (damage-associated molecular patterns) that initiate systemic effects, as well as inflammation and (regulated) secondary brain injury in neighboring tissue. Furthermore, if one mode of cell death is inhibited, another route may step in at least in a scenario when upstream damaging factors predominate over protective responses. The provision of alternative routes through which the cell undergoes death has to be taken into account in the hunt for novel brain protective strategies.

show abstract

Section: Apoptotic Cell Deathmentioning

confidence: 99%

Cell Death in the Developing Brain after Hypoxia-Ischemia

Thornton

Leaw

Mallard

et al. 2017

Front. Cell. Neurosci.

133

View full text Add to dashboard Cite

show abstract

“…In hypoxia–ischemia encephalopathy, Iduna's downregulation is associated with apoptosis-inducing factor nuclear translocation and neuronal cell death, 23 and oxidative stressed-DNA damage activates PARP-1. 24 PARP-1 induces translocation of apoptosis-inducing factor from mitochondria to the nucleus.…”

Section: Discussionmentioning

confidence: 99%

Neuroprotectin D1 upregulates Iduna expression and provides protection in cellular uncompensated oxidative stress and in experimental ischemic stroke

et al. 2017

View full text Add to dashboard Cite

Ring finger protein 146 (Iduna) facilitates DNA repair and protects against cell death induced by NMDA receptor-mediated glutamate excitotoxicity or by cerebral ischemia. Neuroprotectin D1 (NPD1), a docosahexaenoic acid (DHA)-derived lipid mediator, promotes cell survival under uncompensated oxidative stress (UOS). Our data demonstrate that NPD1 potently upregulates Iduna expression and provides remarkable cell protection against UOS. Iduna, which was increased by the lipid mediator, requires the presence of the poly(ADP-ribose) (PAR) sites. Moreover, astrocytes and neurons in the penumbra display an enhanced abundance of Iduna, followed by remarkable neurological protection when DHA, a precursor of NPD1, is systemically administered 1 h after 2 h of ischemic stroke. These findings provide a conceptual advancement for survival of neural cells undergoing challenges to homeostasis because a lipid mediator, made 'on demand,' modulates the abundance of a critically important protein for cell survival.

show abstract

“…Genetic CHCHD4 haploinsufficiency resulted in reduced infarct size and a reduction in caspase‐independent neuronal cell death . Severe HI insult in vivo also results in the loss of the AIF negative regulatory protein Iduna, exacerbating the injury as well as contributing to the development of neurocognitive impairment .…”

Section: Mitochondria Act As Hubs For Development Of Brain Injurymentioning

confidence: 99%

Mitochondrial dynamics, mitophagy and biogenesis in neonatal hypoxic‐ischaemic brain injury

et al. 2017

View full text Add to dashboard Cite

Hypoxic-ischaemic encephalopathy, resulting from asphyxia during birth, affects 2-3 in every 1000 term infants and depending on severity, brings about life-changing neurological consequences or death. This hypoxic-ischaemia (HI) results in a delayed neural energy failure during which the majority of brain injury occurs. Currently, there are limited treatment options and additional therapies are urgently required. Mitochondrial dysfunction acts as a focal point in injury development in the immature brain. Not only do mitochondria become permeabilised, but recent findings implicate perturbations in mitochondrial dynamics (fission, fusion), mitophagy and biogenesis. Mitoprotective therapies may therefore offer a new avenue of intervention for babies who suffer lifelong disabilities due to birth asphyxia.

show abstract

Downregulation of Iduna is associated with AIF nuclear translocation in neonatal brain after hypoxia–ischemia

Cited by 8 publications

References 24 publications

Cell Death in the Developing Brain after Hypoxia-Ischemia

Cell Death in the Developing Brain after Hypoxia-Ischemia

Neuroprotectin D1 upregulates Iduna expression and provides protection in cellular uncompensated oxidative stress and in experimental ischemic stroke

Mitochondrial dynamics, mitophagy and biogenesis in neonatal hypoxic‐ischaemic brain injury

Contact Info

Product

Resources

About