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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

Inhibiting sirt1 decreased the sirt1 increase caused by EGCGSirt1 small interfering RNA (siSirt1) or negative control siRNA (NC) transfected SH-SY5Y cells were incubated with EGCG (10 μM) for 30 hr. Western blot for sirt1 and acetyl-p53 proteins was conducted from SH-SY5Y cells. β-actin was used as the loading control A. Relative sirt1 mRNA expression levels were analyzed using quantitative real-time polymerase chain reaction. The indicated relative gene expression level shows expression levels that were normalized to β-actin expression as the standard B. siSirt1 or NC transfected SH-SY5Y cells were pre-incubated with EGCG (10 μM) for 1 hr and then exposed to PrP (106-126) for 30 hr. Sirt1 deacetylase activities were analyzed in SH-SY5Y cell nuclei. C. Bars indicate mean ± standard error (n = 4). *p < 0.05, **p < 0.01, 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 7: Inhibiting sirt1 decreased the sirt1 increase caused by EGCGSirt1 small interfering RNA (siSirt1) or negative control siRNA (NC) transfected SH-SY5Y cells were incubated with EGCG (10 μM) for 30 hr. Western blot for sirt1 and acetyl-p53 proteins was conducted from SH-SY5Y cells. β-actin was used as the loading control A. Relative sirt1 mRNA expression levels were analyzed using quantitative real-time polymerase chain reaction. The indicated relative gene expression level shows expression levels that were normalized to β-actin expression as the standard B. siSirt1 or NC transfected SH-SY5Y cells were pre-incubated with EGCG (10 μM) for 1 hr and then exposed to PrP (106-126) for 30 hr. Sirt1 deacetylase activities were analyzed in SH-SY5Y cell nuclei. C. Bars indicate mean ± standard error (n = 4). *p < 0.05, **p < 0.01, significant differences between control and each treatment group, and #p < 0.01; significantly different when compared with PrP (106-126)-treated group.

Mentions: We next investigated whether sirt1 knockdown inhibited sirt1 protein levels. SH-SY5Y cells transfected with sirt1 siRNA were treated with 10 μM EGCG. As a result, EGCG increased sirt1 protein levels, which were blocked by sirt1 siRNA. Sirt1 knockdown contributed to p53 deacetylation, and p53 acetylation protein levels decreased in EGCG-treated cells (Figure 7A).


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)

Inhibiting sirt1 decreased the sirt1 increase caused by EGCGSirt1 small interfering RNA (siSirt1) or negative control siRNA (NC) transfected SH-SY5Y cells were incubated with EGCG (10 μM) for 30 hr. Western blot for sirt1 and acetyl-p53 proteins was conducted from SH-SY5Y cells. β-actin was used as the loading control A. Relative sirt1 mRNA expression levels were analyzed using quantitative real-time polymerase chain reaction. The indicated relative gene expression level shows expression levels that were normalized to β-actin expression as the standard B. siSirt1 or NC transfected SH-SY5Y cells were pre-incubated with EGCG (10 μM) for 1 hr and then exposed to PrP (106-126) for 30 hr. Sirt1 deacetylase activities were analyzed in SH-SY5Y cell nuclei. C. Bars indicate mean ± standard error (n = 4). *p < 0.05, **p < 0.01, 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 7: Inhibiting sirt1 decreased the sirt1 increase caused by EGCGSirt1 small interfering RNA (siSirt1) or negative control siRNA (NC) transfected SH-SY5Y cells were incubated with EGCG (10 μM) for 30 hr. Western blot for sirt1 and acetyl-p53 proteins was conducted from SH-SY5Y cells. β-actin was used as the loading control A. Relative sirt1 mRNA expression levels were analyzed using quantitative real-time polymerase chain reaction. The indicated relative gene expression level shows expression levels that were normalized to β-actin expression as the standard B. siSirt1 or NC transfected SH-SY5Y cells were pre-incubated with EGCG (10 μM) for 1 hr and then exposed to PrP (106-126) for 30 hr. Sirt1 deacetylase activities were analyzed in SH-SY5Y cell nuclei. C. Bars indicate mean ± standard error (n = 4). *p < 0.05, **p < 0.01, significant differences between control and each treatment group, and #p < 0.01; significantly different when compared with PrP (106-126)-treated group.
Mentions: We next investigated whether sirt1 knockdown inhibited sirt1 protein levels. SH-SY5Y cells transfected with sirt1 siRNA were treated with 10 μM EGCG. As a result, EGCG increased sirt1 protein levels, which were blocked by sirt1 siRNA. Sirt1 knockdown contributed to p53 deacetylation, and p53 acetylation protein levels decreased in EGCG-treated cells (Figure 7A).

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