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EGCG-mediated autophagy flux has a neuroprotection effect via a class III histone deacetylase in primary neuron cells.

Lee JH, Moon JH, Kim SW, Jeong JK, Nazim UM, Lee YJ, Seol JW, Park SY - Oncotarget (2015)

Bottom Line: The results showed that EGCG protects the neuronal cells against human prion protein-induced damage through inhibiting Bax and cytochrome c translocation and autophagic pathways by increasing LC3-II and reducing and blocking p62 by using ATG5 small interfering (si) RNA and autophagy inhibitors.We further demonstrated that the neuroprotective effects of EGCG were exhibited by a class III histone deacetylase; sirt1 activation and the neuroprotective effects attenuated by sirt1 inactivation using sirt1 siRNA and sirtinol.We demonstrated that EGCG activated the autophagic pathways by inducing sirt1, and had protective effects against human prion protein-induced neuronal cell toxicity.

View Article: PubMed Central - PubMed

Affiliation: Biosafety Research Institute, College of Veterinary Medicine, Chonbuk National University, Jeonju, Jeonbuk, South Korea.

ABSTRACT
Prion diseases caused by aggregated misfolded prion protein (PrP) are transmissible neurodegenerative disorders that occur in both humans and animals. Epigallocatechin-3-gallate (EGCG) has preventive effects on prion disease; however, the mechanisms related to preventing prion diseases are unclear. We investigated whether EGCG, the main polyphenol in green tea, prevents neuron cell damage induced by the human prion protein. We also studied the neuroprotective mechanisms and proper signals mediated by EGCG. The results showed that EGCG protects the neuronal cells against human prion protein-induced damage through inhibiting Bax and cytochrome c translocation and autophagic pathways by increasing LC3-II and reducing and blocking p62 by using ATG5 small interfering (si) RNA and autophagy inhibitors. We further demonstrated that the neuroprotective effects of EGCG were exhibited by a class III histone deacetylase; sirt1 activation and the neuroprotective effects attenuated by sirt1 inactivation using sirt1 siRNA and sirtinol. We demonstrated that EGCG activated the autophagic pathways by inducing sirt1, and had protective effects against human prion protein-induced neuronal cell toxicity. These results suggest that EGCG may be a therapeutic agent for treatment of neurodegenerative disorders including prion diseases.

No MeSH data available.


Related in: MedlinePlus

EGCG prevents neuronal cells from PrP (106-126)-induced cell death through the sirt1 pathwaySirt1 small interfering RNA (siSirt1) or negative control siRNA (NC) transfected SH-SY5Y cells were incubated with 50 μM PrP (106-126) for 36 hr in the presence of EGCG. Cell viability was measured by Annexin V assay A, B. SH-SY5Y cells were pretreated with sirtinol (10 μM) and EGCG (10 μM) for 1 h and then exposed to 50 μM PrP (106-126) for 36 hr. Cell viability was measured by Annexin V assay C. The cells were measured for JC-1 mono form (green) by flow cytometry. M1 represents the population of JC-1 monomeric cells D, E. Bars indicates mean ± standard error (n = 4). *p < 0.05, **p < 0.01, #p < 0.001 significant differences between control and each treatment group, and ##p < 0.01; significantly different when compared with PrP (106-126)-treated group.
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Figure 6: EGCG prevents neuronal cells from PrP (106-126)-induced cell death through the sirt1 pathwaySirt1 small interfering RNA (siSirt1) or negative control siRNA (NC) transfected SH-SY5Y cells were incubated with 50 μM PrP (106-126) for 36 hr in the presence of EGCG. Cell viability was measured by Annexin V assay A, B. SH-SY5Y cells were pretreated with sirtinol (10 μM) and EGCG (10 μM) for 1 h and then exposed to 50 μM PrP (106-126) for 36 hr. Cell viability was measured by Annexin V assay C. The cells were measured for JC-1 mono form (green) by flow cytometry. M1 represents the population of JC-1 monomeric cells D, E. Bars indicates mean ± standard error (n = 4). *p < 0.05, **p < 0.01, #p < 0.001 significant differences between control and each treatment group, and ##p < 0.01; significantly different when compared with PrP (106-126)-treated group.

Mentions: Furthermore, sirt1 siRNA was used to knockdown sirt1 gene expression, to confirm that EGCG protects against prion-induced apoptosis by activating sirt1 and increasing sirt1 expression. We found that knockdown of sirt1 expression blocked the neuronal protective effects caused by EGCG, which inhibited neurotoxicity by PrP (106-126) (Figure 6A and 6B). No EGCG mediated-neuroprotective effects were observed when sirt1 activation was inhibited by sirtinol (sirt1 activation inhibitor) (Figure 6C). These results show that the protective effect on the MTP by activating sirt1 was inhibited by transfection with sirt1 siRNA. The SH-SY5Y cells pre-treated with EGCG 10 μM and exposed to 50 μM PrP (106-126) decreased PrP (106-126)-induced JC-1 monomer fluorescence intensity, whereas cells transfected with sirt1 siRNA increased JC-1 monomer fluorescence intensity (Figure 6D and 6E).


EGCG-mediated autophagy flux has a neuroprotection effect via a class III histone deacetylase in primary neuron cells.

Lee JH, Moon JH, Kim SW, Jeong JK, Nazim UM, Lee YJ, Seol JW, Park SY - Oncotarget (2015)

EGCG prevents neuronal cells from PrP (106-126)-induced cell death through the sirt1 pathwaySirt1 small interfering RNA (siSirt1) or negative control siRNA (NC) transfected SH-SY5Y cells were incubated with 50 μM PrP (106-126) for 36 hr in the presence of EGCG. Cell viability was measured by Annexin V assay A, B. SH-SY5Y cells were pretreated with sirtinol (10 μM) and EGCG (10 μM) for 1 h and then exposed to 50 μM PrP (106-126) for 36 hr. Cell viability was measured by Annexin V assay C. The cells were measured for JC-1 mono form (green) by flow cytometry. M1 represents the population of JC-1 monomeric cells D, E. Bars indicates mean ± standard error (n = 4). *p < 0.05, **p < 0.01, #p < 0.001 significant differences between control and each treatment group, and ##p < 0.01; significantly different when compared with PrP (106-126)-treated group.
© Copyright Policy - open-access
Related In: Results  -  Collection

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Figure 6: EGCG prevents neuronal cells from PrP (106-126)-induced cell death through the sirt1 pathwaySirt1 small interfering RNA (siSirt1) or negative control siRNA (NC) transfected SH-SY5Y cells were incubated with 50 μM PrP (106-126) for 36 hr in the presence of EGCG. Cell viability was measured by Annexin V assay A, B. SH-SY5Y cells were pretreated with sirtinol (10 μM) and EGCG (10 μM) for 1 h and then exposed to 50 μM PrP (106-126) for 36 hr. Cell viability was measured by Annexin V assay C. The cells were measured for JC-1 mono form (green) by flow cytometry. M1 represents the population of JC-1 monomeric cells D, E. Bars indicates mean ± standard error (n = 4). *p < 0.05, **p < 0.01, #p < 0.001 significant differences between control and each treatment group, and ##p < 0.01; significantly different when compared with PrP (106-126)-treated group.
Mentions: Furthermore, sirt1 siRNA was used to knockdown sirt1 gene expression, to confirm that EGCG protects against prion-induced apoptosis by activating sirt1 and increasing sirt1 expression. We found that knockdown of sirt1 expression blocked the neuronal protective effects caused by EGCG, which inhibited neurotoxicity by PrP (106-126) (Figure 6A and 6B). No EGCG mediated-neuroprotective effects were observed when sirt1 activation was inhibited by sirtinol (sirt1 activation inhibitor) (Figure 6C). These results show that the protective effect on the MTP by activating sirt1 was inhibited by transfection with sirt1 siRNA. The SH-SY5Y cells pre-treated with EGCG 10 μM and exposed to 50 μM PrP (106-126) decreased PrP (106-126)-induced JC-1 monomer fluorescence intensity, whereas cells transfected with sirt1 siRNA increased JC-1 monomer fluorescence intensity (Figure 6D and 6E).

Bottom Line: The results showed that EGCG protects the neuronal cells against human prion protein-induced damage through inhibiting Bax and cytochrome c translocation and autophagic pathways by increasing LC3-II and reducing and blocking p62 by using ATG5 small interfering (si) RNA and autophagy inhibitors.We further demonstrated that the neuroprotective effects of EGCG were exhibited by a class III histone deacetylase; sirt1 activation and the neuroprotective effects attenuated by sirt1 inactivation using sirt1 siRNA and sirtinol.We demonstrated that EGCG activated the autophagic pathways by inducing sirt1, and had protective effects against human prion protein-induced neuronal cell toxicity.

View Article: PubMed Central - PubMed

Affiliation: Biosafety Research Institute, College of Veterinary Medicine, Chonbuk National University, Jeonju, Jeonbuk, South Korea.

ABSTRACT
Prion diseases caused by aggregated misfolded prion protein (PrP) are transmissible neurodegenerative disorders that occur in both humans and animals. Epigallocatechin-3-gallate (EGCG) has preventive effects on prion disease; however, the mechanisms related to preventing prion diseases are unclear. We investigated whether EGCG, the main polyphenol in green tea, prevents neuron cell damage induced by the human prion protein. We also studied the neuroprotective mechanisms and proper signals mediated by EGCG. The results showed that EGCG protects the neuronal cells against human prion protein-induced damage through inhibiting Bax and cytochrome c translocation and autophagic pathways by increasing LC3-II and reducing and blocking p62 by using ATG5 small interfering (si) RNA and autophagy inhibitors. We further demonstrated that the neuroprotective effects of EGCG were exhibited by a class III histone deacetylase; sirt1 activation and the neuroprotective effects attenuated by sirt1 inactivation using sirt1 siRNA and sirtinol. We demonstrated that EGCG activated the autophagic pathways by inducing sirt1, and had protective effects against human prion protein-induced neuronal cell toxicity. These results suggest that EGCG may be a therapeutic agent for treatment of neurodegenerative disorders including prion diseases.

No MeSH data available.


Related in: MedlinePlus