Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: UNIPROT:P10415 (
Bcl-2
)
33,771
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Oxidative stress and iron accumulation are tightly associated with neurodegenerative diseases. Mitochondrial ferritin (FtMt) is identified as an iron-storage protein located in the mitochondria, and its role in regulation of iron hemeostasis in neurodegenerative diseases has been reported. However, the role of FtMt in hydrogen peroxide (H
2
O
2
)-induced oxidative stress and iron accumulation in neuronal cells has not been studied. Here, we overexpressed FtMt in neuroblastoma SH-SY5Y cells and induced oxidative stress by treating with extracellular H
2
O
2
. We found that overexpression of FtMt significantly prevented cell death induced by H
2
O
2
, particularly the apoptosis-dependent cell death. The protective effects involved inhibiting the generation of cellular reactive oxygen species, sustaining mitochondrial membrane potential, maintaining the level of anti-apoptotic protein
Bcl-2
, and inhibiting the activation of pro-apoptotic protein caspase 3. We further explored the mechanism of these protective effects and found that FtMt expression markedly altered iron homeostasis of the H
2
O
2
treated cells as compared to that of controls. The FtMt overexpression significantly reduced cellular labile iron pool (LIP) and protected H
2
O
2
-induced elevation on LIP. While in H
2
O
2
treated SH-SY5Y cells, the increased iron uptake and reduced iron release, in correlation with levels of
DMT1
(-IRE) and ferroportin 1, resulted in heavy iron accumulation, the FtMt overexpressing cells didn't show any significant changes in levels of iron transport proteins and in the level of LIP. These results implicate a neuroprotective role of FtMt on H
2
O
2
-induced oxidative stress, which may provide insights into the treatment of iron accumulation associated neurodegenerative diseases.
...
PMID:Mitochondrial Ferritin Protects Hydrogen Peroxide-Induced Neuronal Cell Damage. 2884 60
Recent researches suggested that iron dysregulation play an important role in the pathogenesis of vascular dementia (VD). Iron deposition had been found in hippocampus in vascular dementia model in recent research. Nevertheless, the underlying mechanisms of iron deposition and its neurotoxicity in vascular dementia was still unclear. Thus, our research was aimed at whether the neurotoxicity of iron was associated with autophagy regulation. We established a chronic cerebral hypoperfusion model in the rat brain in order to mimic the vascular dementia using permanent bilateral common carotid artery occlusion (2VO). The preparation of iron overloaded rats model by intraperitoneal injection of iron dextran. Following, we tested the learning and memory function of each group using Morris Water Maze. Consequently, we analyzed the iron content and iron transport related molecules (TFR1,
DMT1
) in hippocampus. Furthermore, we examined the effect of iron deposition on autophagy-related molecules including AMPK, Beclin1 and LC3 and the number of autophagosomes in hippocampus. Last, we tested the apoptosis of neurons in hippocampus. We found that iron deposition in hippocampus in model groups which accompanied the decline of learning and memory function. And the expression of TFR1 and
DMT1
were up-regulated in model groups. Moreover, iron deposition up-regulated the expression of AMPK, Beclin1 and LC3 and increase the number of autophagosomes in hippocampus. And the expression of Bax was up-regulated and
Bcl-2
was down-regulated in iron deposition groups. To sum up, our data suggested that iron deposition increased AMPK/autophagy pathway associated molecules in the hippocampus and promoted neuronal apoptosis, which might be a new pathogenesis in vascular dementia.
...
PMID:Iron dysregulation in vascular dementia: Focused on the AMPK/autophagy pathway. 3154 26
