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Therapeutic potential of human amniotic membrane-derived mesenchymal stem cells in APP transgenic mice

View Article: PubMed Central - PubMed

ABSTRACT

Growing evidence indicates that the presence of extensive oxidative stress plays an essential role in the initiation and progression of Alzheimer's disease (AD). Amyloid-β (Aβ) aggregation is involved in the elevation of oxidative stress, contributing to mitochondrial dysfunction and lipid peroxidation. In the present study, human placenta amniotic membrane-derived mesenchymal stem cells (hAMMSCs) were intravenously injected into C57BL/6J-APP transgenic mice. hAMMSCs significantly ameliorated spatial learning and memory function, and were associated with a decreased amount of amyloid plaques of the brain. The correlation of oxidative stress with Aβ levels was lower in the hAMMSCs-injected group than in the phosphate-buffered saline (PBS)-injected group, as indicated by the increased level of antioxidative enzymes and the decreased level of lipid peroxidation product. The glutathione (GSH) level and ratio of GSH to glutathione disulfide were higher in the hAMMSC group than in the PBS group. The superoxide dismutase activity and malonaldehyde level were improved significantly as the level of Aβ decreased, but there was no such trend in the PBS group. As a result, our findings represent evidence that hAMMSC treatment might improve the pathology of AD and memory function through the regulation of oxidative stress.

No MeSH data available.


Related in: MedlinePlus

Human amniotic membrane-derived mesenchymal stem cells (hAMMSCs) reduced oxidative stress in Alzheimer's disease (AD) transgenic mice. The levels of (A) glutathione disulfide (GSSG), (B) glutathione (GSH), (C) the extent of lipid peroxidation malonaldehyde (MDA) and (D) the activity of antioxidant enzyme superoxide dismutase (SOD) were measured by assay kit spectrophotometrically. (E) The GSH/GSSG ratio was calculated. *P<0.05 vs. phosphate-buffered saline (PBS)-treated control group. WT, negative control group.
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f5-ol-0-0-4857: Human amniotic membrane-derived mesenchymal stem cells (hAMMSCs) reduced oxidative stress in Alzheimer's disease (AD) transgenic mice. The levels of (A) glutathione disulfide (GSSG), (B) glutathione (GSH), (C) the extent of lipid peroxidation malonaldehyde (MDA) and (D) the activity of antioxidant enzyme superoxide dismutase (SOD) were measured by assay kit spectrophotometrically. (E) The GSH/GSSG ratio was calculated. *P<0.05 vs. phosphate-buffered saline (PBS)-treated control group. WT, negative control group.

Mentions: Oxidative stress was proposed as an essential factor contributing to Aβ neurotoxicity, which occurs at the prophase of AD prior to the onset of clinical and pathological symptoms (25). Aβ deposition in the brain parenchyma causes lipid peroxidation and protein oxidation, damaging the mitochondria and resulting in the loss of oxidative function of significant proteins in numerous pathways, including glucose metabolic proteins and death of neurons (26). Since hAMMSC transplantation attenuated the deposition of Aβ, we further investigated whether hAMMSCs could decrease oxidative stress in AD mice. GSH acts as a crucial cellular antioxidant against oxidative stress by reducing hydrogen peroxides and hydroperoxides in addition to protecting protein thiol groups against oxidation (27). GSH is converted into GSSG by GPx to detoxify peroxides, and the reaction could be converted back by glutathione reductase. It is considered that the ratio of GSH/GSSG reflects the intracellular antioxidant level. Following the transplantation of hAMMSCs in AD transgenic mice, the GSH level was increased significantly but the GSSG level was only slightly lowered in brain homogenates (Fig. 5A and B). The GSH/GSSG ratio in the hAMMSC group was significantly elevated compared with that of the PBS group (Fig. 5C).


Therapeutic potential of human amniotic membrane-derived mesenchymal stem cells in APP transgenic mice
Human amniotic membrane-derived mesenchymal stem cells (hAMMSCs) reduced oxidative stress in Alzheimer's disease (AD) transgenic mice. The levels of (A) glutathione disulfide (GSSG), (B) glutathione (GSH), (C) the extent of lipid peroxidation malonaldehyde (MDA) and (D) the activity of antioxidant enzyme superoxide dismutase (SOD) were measured by assay kit spectrophotometrically. (E) The GSH/GSSG ratio was calculated. *P<0.05 vs. phosphate-buffered saline (PBS)-treated control group. WT, negative control group.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4998013&req=5

f5-ol-0-0-4857: Human amniotic membrane-derived mesenchymal stem cells (hAMMSCs) reduced oxidative stress in Alzheimer's disease (AD) transgenic mice. The levels of (A) glutathione disulfide (GSSG), (B) glutathione (GSH), (C) the extent of lipid peroxidation malonaldehyde (MDA) and (D) the activity of antioxidant enzyme superoxide dismutase (SOD) were measured by assay kit spectrophotometrically. (E) The GSH/GSSG ratio was calculated. *P<0.05 vs. phosphate-buffered saline (PBS)-treated control group. WT, negative control group.
Mentions: Oxidative stress was proposed as an essential factor contributing to Aβ neurotoxicity, which occurs at the prophase of AD prior to the onset of clinical and pathological symptoms (25). Aβ deposition in the brain parenchyma causes lipid peroxidation and protein oxidation, damaging the mitochondria and resulting in the loss of oxidative function of significant proteins in numerous pathways, including glucose metabolic proteins and death of neurons (26). Since hAMMSC transplantation attenuated the deposition of Aβ, we further investigated whether hAMMSCs could decrease oxidative stress in AD mice. GSH acts as a crucial cellular antioxidant against oxidative stress by reducing hydrogen peroxides and hydroperoxides in addition to protecting protein thiol groups against oxidation (27). GSH is converted into GSSG by GPx to detoxify peroxides, and the reaction could be converted back by glutathione reductase. It is considered that the ratio of GSH/GSSG reflects the intracellular antioxidant level. Following the transplantation of hAMMSCs in AD transgenic mice, the GSH level was increased significantly but the GSSG level was only slightly lowered in brain homogenates (Fig. 5A and B). The GSH/GSSG ratio in the hAMMSC group was significantly elevated compared with that of the PBS group (Fig. 5C).

View Article: PubMed Central - PubMed

ABSTRACT

Growing evidence indicates that the presence of extensive oxidative stress plays an essential role in the initiation and progression of Alzheimer's disease (AD). Amyloid-&beta; (A&beta;) aggregation is involved in the elevation of oxidative stress, contributing to mitochondrial dysfunction and lipid peroxidation. In the present study, human placenta amniotic membrane-derived mesenchymal stem cells (hAMMSCs) were intravenously injected into C57BL/6J-APP transgenic mice. hAMMSCs significantly ameliorated spatial learning and memory function, and were associated with a decreased amount of amyloid plaques of the brain. The correlation of oxidative stress with A&beta; levels was lower in the hAMMSCs-injected group than in the phosphate-buffered saline (PBS)-injected group, as indicated by the increased level of antioxidative enzymes and the decreased level of lipid peroxidation product. The glutathione (GSH) level and ratio of GSH to glutathione disulfide were higher in the hAMMSC group than in the PBS group. The superoxide dismutase activity and malonaldehyde level were improved significantly as the level of A&beta; decreased, but there was no such trend in the PBS group. As a result, our findings represent evidence that hAMMSC treatment might improve the pathology of AD and memory function through the regulation of oxidative stress.

No MeSH data available.


Related in: MedlinePlus