Resveratrol provides neuroprotective effects through modulation of mitochondrial dynamics and ERK1/2 regulated autophagy

被引：70

作者：

Lin, Kai-Lieh ^{[1
,2
,3
]}

Lin, Kai-Jung ^{[1
,2
,4
]}

Wang, Pei-Wen ^{[1
,2
,5
]}

Chuang, Jiin-Haur ^{[1
,2
,6
]}

Lin, Hung-Yu ^{[1
,2
,7
,8
]}

Chen, Shang-Der ^{[1
,2
,7
,8
]}

Chuang, Yao-Chung ^{[1
,2
,7
,8
]}

Huang, Sheng-Teng ^{[1
,2
,9
]}

Tiao, Mao-Meng ^{[1
,2
,10
]}

Chen, Jin-Bor ^{[1
,2
,11
]}

Huang, Pei-Hsuan ^{[1
,2
,7
]}

Liou, Chia-Wei ^{[1
,2
,7
,8
,12
]}

Lin, Tsu-Kung ^{[1
,2
,7
,8
,12
]}

机构：

[1] Kaohsiung Chang Gung Mem Hosp, Mitochondrial Res Unit, Kaohsiung 833, Taiwan

[2] Chang Gung Univ, Coll Med, Kaohsiung 833, Taiwan

[3] Tzu Chi Univ, Dept Med, Hualien 970, Taiwan

[4] Taipei Med Univ, Dept Med, Taipei 110, Taiwan

[5] Kaohsiung Chang Gung Mem Hosp, Dept Internal Med, Kaohsiung 833, Taiwan

[6] Kaohsiung Chang Gung Mem Hosp, Div Pediat Surg, Kaohsiung 833, Taiwan

[7] Kaohsiung Chang Gung Mem Hosp, Dept Neurol, Kaohsiung 833, Taiwan

[8] Kaohsiung Chang Gung Mem Hosp, Ctr Parkinsons Dis, Kaohsiung 833, Taiwan

[9] Kaohsiung Chang Gung Mem Hosp, Dept Chinese Med, Kaohsiung 833, Taiwan

[10] Kaohsiung Chang Gung Mem Hosp, Dept Pediat, Kaohsiung 833, Taiwan

[11] Kaohsiung Chang Gung Mem Hosp, Dept Nephrol, Kaohsiung 833, Taiwan

[12] Chang Gung Univ, Kaohsiung Chang Gung Mem Hosp, Coll Med, Kaohsiung, Taiwan

来源：

FREE RADICAL RESEARCH | 2018年 / 52卷 / 11-12期

关键词：

Autophagy; ERK1/2; mitochondrial dynamics; oxidative stress; Parkinson's disease; resveratrol; OXIDATIVE STRESS; PARKINSONS-DISEASE; RAT MODEL; FISSION; FUSION; DYSFUNCTION; MITOPHAGY; LC3; PHOSPHORYLATION; DEGRADATION;

D O I：

10.1080/10715762.2018.1489128

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Mitochondrial dysfunction and oxidative stress are underlying contributors to Parkinson's disease (PD). The reduction of aberrant proteins and dysfunctional mitochondria through constitutive autophagy is essential for neuronal survival. We investigated the neuroprotective effects of the natural red wine extract, resveratrol, on the Complex I inhibitor, rotenone-induced oxidative stress SH-SY5Y cellular model. With rotenone exposure, cellular reactive oxygen species (ROS), apoptosis and cell death increased at both 6 and 18 h; at the same time, mitochondrial membrane potential (Delta psi m) and the balance of mitochondrial dynamic proteins were disrupted, resulting with fragmented mitochondria. Rotenone was also noted to elevate autophagy initiation but downregulate the autophagy flux. Pretreatment with resveratrol to rotenone exposed cells lowered cellular ROS, apoptosis, and increased survival rates. Resveratrol administration also recovered rotenone induced Delta psi m, mitochondria dynamics alteration, and elongated fragmented mitochondria. Both autophagic induction and autophagic flux were enhanced with resveratrol pre-treatment which is compatible with cellular survival. The mitogen-activated protein kinase (MEK) inhibitor, U0126, abolished the rescuing effect of resveratrol on rotenone treated neurons through the inhibition of autophagy flux. Thus, our work implies that the neuroprotective effect of resveratrol works in part through modulation of mitochondria dynamics and upregulating autophagic flux via the MEK/extracellular signal-regulated kinase (ERK) signalling pathway.

引用

页码：1371 / 1386

页数：16

共 81 条

[11] S-Nitrosylation of Drp1 Mediates β-Amyloid-Related Mitochondrial Fission and Neuronal Injury [J].