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Secreted miR-34a in astrocytic shedding vesicles enhanced the vulnerability of dopaminergic neurons to neurotoxins by targeting Bcl-2.

Mao S, Sun Q, Xiao H, Zhang C, Li L - Protein Cell (2015)

Bottom Line: To elucidate the potential role of glial MVs in disease, we evaluated the effects of secreted astrocytic MVs on stress condition.Further investigation showed that increased astrocytic miR-34a in SVs was involved in this progress via targeting anti-apoptotic protein Bcl-2 in dopaminergic neurons.These data revealed a novel mechanism underlying astrocyte-neuron interaction in disease.

View Article: PubMed Central - PubMed

Affiliation: State Key Laboratory of Pharmaceutical Biotechnology, Nanjing Advanced Institute for Life Sciences (NAILS), Nanjing University School of Life Sciences, Nanjing, 210093, China.

ABSTRACT
MicroRNAs (miRNAs) are a class of noncoding RNAs that regulates target gene expression at posttranscriptional level, leading to further biological functions. We have demonstrated that microvesicles (MVs) can deliver miRNAs into target cells as a novel way of intercellular communication. It is reported that in central nervous system, glial cells release MVs, which modulate neuronal function in normal condition. To elucidate the potential role of glial MVs in disease, we evaluated the effects of secreted astrocytic MVs on stress condition. Our results demonstrated that after Lipopolysaccharide (LPS) stimulation, astrocytes released shedding vesicles (SVs) that enhanced vulnerability of dopaminergic neurons to neurotoxin. Further investigation showed that increased astrocytic miR-34a in SVs was involved in this progress via targeting anti-apoptotic protein Bcl-2 in dopaminergic neurons. We also found that inhibition of astrocytic miR-34a after LPS stimulation can postpone dopaminergic neuron loss under neurotoxin stress. These data revealed a novel mechanism underlying astrocyte-neuron interaction in disease.

No MeSH data available.


Related in: MedlinePlus

Morphology and characterization of purified microvesicles of U-87 MG cells. (A) EM imaging of purified shedding vesicles secreted by U-87 MG cells (arrows, scale bar = 100 nm); (B) EM imaging of purified exosomes secreted by U-87 MG cells (arrows, scale bar = 100 nm); (C) Western blot of the molecular markers of shedding vesicles (Ribophorin and β1 integrin) and exosomes (CD63 and HSP70); both types of microvesicles contained the miRNA-associated protein Ago2
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Fig1: Morphology and characterization of purified microvesicles of U-87 MG cells. (A) EM imaging of purified shedding vesicles secreted by U-87 MG cells (arrows, scale bar = 100 nm); (B) EM imaging of purified exosomes secreted by U-87 MG cells (arrows, scale bar = 100 nm); (C) Western blot of the molecular markers of shedding vesicles (Ribophorin and β1 integrin) and exosomes (CD63 and HSP70); both types of microvesicles contained the miRNA-associated protein Ago2

Mentions: We collected the shedding vesicles (SVs) and exosomes from the culture medium by differential ultracentrifugation. EM imaging showed the different sizes of the distinct types of microvesicles. SVs consisted of cup-shaped vesicles in the range of 100–200 nm, while exosomes contained relatively small vesicles of approximately 30–80 nm (Fig. 1A and 1B).Figure 1


Secreted miR-34a in astrocytic shedding vesicles enhanced the vulnerability of dopaminergic neurons to neurotoxins by targeting Bcl-2.

Mao S, Sun Q, Xiao H, Zhang C, Li L - Protein Cell (2015)

Morphology and characterization of purified microvesicles of U-87 MG cells. (A) EM imaging of purified shedding vesicles secreted by U-87 MG cells (arrows, scale bar = 100 nm); (B) EM imaging of purified exosomes secreted by U-87 MG cells (arrows, scale bar = 100 nm); (C) Western blot of the molecular markers of shedding vesicles (Ribophorin and β1 integrin) and exosomes (CD63 and HSP70); both types of microvesicles contained the miRNA-associated protein Ago2
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4491052&req=5

Fig1: Morphology and characterization of purified microvesicles of U-87 MG cells. (A) EM imaging of purified shedding vesicles secreted by U-87 MG cells (arrows, scale bar = 100 nm); (B) EM imaging of purified exosomes secreted by U-87 MG cells (arrows, scale bar = 100 nm); (C) Western blot of the molecular markers of shedding vesicles (Ribophorin and β1 integrin) and exosomes (CD63 and HSP70); both types of microvesicles contained the miRNA-associated protein Ago2
Mentions: We collected the shedding vesicles (SVs) and exosomes from the culture medium by differential ultracentrifugation. EM imaging showed the different sizes of the distinct types of microvesicles. SVs consisted of cup-shaped vesicles in the range of 100–200 nm, while exosomes contained relatively small vesicles of approximately 30–80 nm (Fig. 1A and 1B).Figure 1

Bottom Line: To elucidate the potential role of glial MVs in disease, we evaluated the effects of secreted astrocytic MVs on stress condition.Further investigation showed that increased astrocytic miR-34a in SVs was involved in this progress via targeting anti-apoptotic protein Bcl-2 in dopaminergic neurons.These data revealed a novel mechanism underlying astrocyte-neuron interaction in disease.

View Article: PubMed Central - PubMed

Affiliation: State Key Laboratory of Pharmaceutical Biotechnology, Nanjing Advanced Institute for Life Sciences (NAILS), Nanjing University School of Life Sciences, Nanjing, 210093, China.

ABSTRACT
MicroRNAs (miRNAs) are a class of noncoding RNAs that regulates target gene expression at posttranscriptional level, leading to further biological functions. We have demonstrated that microvesicles (MVs) can deliver miRNAs into target cells as a novel way of intercellular communication. It is reported that in central nervous system, glial cells release MVs, which modulate neuronal function in normal condition. To elucidate the potential role of glial MVs in disease, we evaluated the effects of secreted astrocytic MVs on stress condition. Our results demonstrated that after Lipopolysaccharide (LPS) stimulation, astrocytes released shedding vesicles (SVs) that enhanced vulnerability of dopaminergic neurons to neurotoxin. Further investigation showed that increased astrocytic miR-34a in SVs was involved in this progress via targeting anti-apoptotic protein Bcl-2 in dopaminergic neurons. We also found that inhibition of astrocytic miR-34a after LPS stimulation can postpone dopaminergic neuron loss under neurotoxin stress. These data revealed a novel mechanism underlying astrocyte-neuron interaction in disease.

No MeSH data available.


Related in: MedlinePlus