The role of elevated autophagy on the synaptic plasticity impairment caused by CdSe/ZnS quantum dots

Chen, Liang; Miao, Yanyan; Chen, Lin; Jin, Peipei; Zha, Yingying; Chai, Yuming; Zheng, Fang; Zhang, Yunjiao; Zhou, Wei; Zhang, Jigui; Wen, Longping; Wang, Ming

doi:10.1016/j.biomaterials.2013.09.048

Cited by 64 publications

(40 citation statements)

References 52 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Akt is sensitive to the cell metabolic state to control the mTORC1 complex, which in turn controls metabolism, the insulin pathway [35,36], autophagy [37,38] in the nervous system as well as neurogenesis [39], neuron survival [40,41], axon elongation and growth [42–44] and IGF1 induced neuroprotection [45]. Our observed higher Akt levels in the non-Tg neurons may indicate the overall healthier metabolic state of these neurons compared to the 3xTg-AD neurons with higher resting calcium [46,47]; anything that contributes to stronger bioenergetics will maximize function of calcium pumps.…”

Section: 4 Discussionmentioning

confidence: 99%

External cys/cySS Redox State Modification Controls the Intracellular Redox State and Neurodegeneration via Akt in Aging and Alzheimer's Disease Mouse Model Neurons

Ghosh

Brewer

2014

JAD

View full text Add to dashboard Cite

The extracellular redox environment of cells is mainly set by the redox couple cysteine/cystine (cys/cySS) while intracellular redox is buffered by reduced/oxidized glutathione (GSH/GSSG), but controlled by NAD(P)H/NAD(P). With aging, the extracellular redox environment shifts in the oxidized direction beyond middle-age. Since aging is the primary risk factor in Alzheimer’s disease (AD), here our aim was to determine if a reduced extracellular cys/cySS redox potential of cultured primary mouse neurons changes the intracellular redox environment, affects pAkt levels and protects against neuron loss. A reductive shift in cys/cySS in the extracellular medium of neuron cultures from young (4 month) and old (21 month) neurons from non-Tg (non-transgenic) and triple transgenic AD-like mice (3xTg-AD), caused an increase in intracellular NAD(P)H and GSH levels along with lower ROS levels. Importantly, the imposed reductive shift decreased neuron death markedly in the 21 month neurons of both genotypes. Moreover, a reduced cys/cySS redox state increased the pAkt/Akt ratio in 21 month aging and AD-like neurons that positively correlated with a decreased neuron loss. Our findings demonstrate that manipulating the extracellular redox environment toward a more reduced redox potential is neuroprotective in both aging and AD-like neurons and may be a powerful and pragmatic therapeutic tool in aging and age-related diseases like AD.

show abstract

Section: 4 Discussionmentioning

confidence: 99%

External cys/cySS Redox State Modification Controls the Intracellular Redox State and Neurodegeneration via Akt in Aging and Alzheimer's Disease Mouse Model Neurons

Ghosh

Brewer

2014

JAD

View full text Add to dashboard Cite

show abstract

“…In the articles, GNPs were reported to induce various cellular responses, such as necrosis, autophagy, apoptosis, altered gene expression, cell cycle disruption, and oxidative stress. 15,[18][19][20][21][22] Autophagy (generally thought to be a survival mechanism) could be induced by many cytotoxic stimuli, including various types of nanoparticles, [23][24][25][26] but it is still unclear whether autophagy plays a prosurvival or a prodeath role under some specific circumstances, such as hypoxic.…”

Section: Introductionmentioning

confidence: 99%

Overendocytosis of gold nanoparticles increases autophagy and apoptosis in hypoxic human renal proximal tubular cells

Fan¹,

Li²,

Liu³

et al. 2014

IJN

View full text Add to dashboard Cite

Background Gold nanoparticles (GNPs) can potentially be used in biomedical fields ranging from therapeutics to diagnostics, and their use will result in increased human exposure. Many studies have demonstrated that GNPs can be deposited in the kidneys, particularly in renal tubular epithelial cells. Chronic hypoxic is inevitable in chronic kidney diseases, and it results in renal tubular epithelial cells that are susceptible to different types of injuries. However, the understanding of the interactions between GNPs and hypoxic renal tubular epithelial cells is still rudimentary. In the present study, we characterized the cytotoxic effects of GNPs in hypoxic renal tubular epithelial cells. Results Both 5 nm and 13 nm GNPs were synthesized and characterized using various biophysical methods, including transmission electron microscopy, dynamic light scattering, and ultraviolet–visible spectrophotometry. We detected the cytotoxicity of 5 and 13 nm GNPs (0, 1, 25, and 50 nM) to human renal proximal tubular cells (HK-2) by Cell Counting Kit-8 assay and lactate dehydrogenase release assay, but we just found the toxic effect in the 5 nm GNP-treated cells at 50 nM dose under hypoxic condition. Furthermore, the transmission electron microscopy images revealed that GNPs were either localized in vesicles or free in the lysosomes in 5 nm GNPs-treated HK-2 cells, and the cellular uptake of the GNPs in the hypoxic cells was significantly higher than that in normoxic cells. In normoxic HK-2 cells, 5 nm GNPs (50 nM) treatment could cause autophagy and cell survival. However, in hypoxic conditions, the GNP exposure at the same condition led to the production of reactive oxygen species, the loss of mitochondrial membrane potential (ΔΨM), and an increase in apoptosis and autophagic cell death. Conclusion/significance Our results demonstrate that renal tubular epithelial cells presented different responses under normoxic and hypoxic environments, which provide an important basis for understanding the risks associated with GNP use–especially for the potential GNP-related therapies in chronic kidney disease patients.

show abstract

“…For example, in the deprival of nutrients, cells are undergoing autophagy, which recycles Although some nanoparticles are believed to be biocompatible, it may vary depending on the nature of nanoparticles themselves and the cell types. For example, silica nanoparticles and CdSe/ZnS quantum dots can induce autophagy in A549 cells 6 in synapse, 18 respectively. In our present study, we found Fe 3 O 4 NPs activate autophagy in both normal and malignant blood cells.…”

Section: Discussionmentioning

confidence: 99%

Ferroferric oxide nanoparticles induce prosurvival autophagy in human blood cells by modulating the Beclin 1/Bcl-2/VPS34 complex

Shi¹,

Cheng²,

Zhang³

et al. 2014

IJN

View full text Add to dashboard Cite

Magnetic iron oxide nanoparticles (NPs) are emerging as novel materials with great potentials for various biomedical applications, but their biological activities are largely unknown. In the present study, we found that ferroferric oxide nanoparticles (Fe 3 O 4 NPs) induced autophagy in blood cells. Both naked and modified Fe 3 O 4 NPs induced LC3 lipidation and degraded p62, a monitor of autophagy flux. And this change could be abolished by autophagy inhibitors. Mechanistically, Fe 3 O 4 NP-induced autophagy was accompanied by increased Beclin 1 and VPS34 and decreased Bcl-2, thus promoting the formation of the critical complex in autophagy initiation. Further studies demonstrated that Fe 3 O 4 NPs attenuated cell death induced by anticancer drugs bortezomib and doxorubicin. Therefore, this study suggested that Fe 3 O 4 NPs can induce prosurvival autophagy in blood cells by modulating the Beclin l/Bcl-2/VPS34 complex. This study suggests that caution should be taken when Fe 3 O 4 NPs are used in blood cancer patients.

show abstract

The role of elevated autophagy on the synaptic plasticity impairment caused by CdSe/ZnS quantum dots

Cited by 64 publications

References 52 publications

External cys/cySS Redox State Modification Controls the Intracellular Redox State and Neurodegeneration via Akt in Aging and Alzheimer's Disease Mouse Model Neurons

External cys/cySS Redox State Modification Controls the Intracellular Redox State and Neurodegeneration via Akt in Aging and Alzheimer's Disease Mouse Model Neurons

Overendocytosis of gold nanoparticles increases autophagy and apoptosis in hypoxic human renal proximal tubular cells

Ferroferric oxide nanoparticles induce prosurvival autophagy in human blood cells by modulating the Beclin 1/Bcl-2/VPS34 complex

Contact Info

Product

Resources

About

The role of elevated autophagy on the synaptic plasticity impairment caused by CdSe/ZnS quantum dots

Cited by 64 publications

References 52 publications

External cys/cySS Redox State Modification Controls the Intracellular Redox State and Neurodegeneration via Akt in Aging and Alzheimer's Disease Mouse Model Neurons

External cys/cySS Redox State Modification Controls the Intracellular Redox State and Neurodegeneration via Akt in Aging and Alzheimer's Disease Mouse Model Neurons

Overendocytosis of gold nanoparticles increases autophagy and apoptosis in hypoxic human renal proximal tubular cells

Ferroferric oxide nanoparticles induce prosurvival autophagy in human blood cells by modulating the&nbsp;Beclin 1/Bcl-2/VPS34 complex

Contact Info

Product

Resources

About

Ferroferric oxide nanoparticles induce prosurvival autophagy in human blood cells by modulating the Beclin 1/Bcl-2/VPS34 complex