Mitochondrial Effects of PGC-1alpha Silencing in MPP+ Treated Human SH-SY5Y Neuroblastoma Cells

Ye, Qinyong; Chen, Chun; Si, Erwang; Cai, Yuanfeng; Wang, Juhua; Huang, Wei-Chao; Li, Dongzhu; Wang, Ying-Qing; Chen, Xiaochun

doi:10.3389/fnmol.2017.00164

Cited by 31 publications

(32 citation statements)

References 41 publications

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“…Totally, studies on changes in PGC1α levels have provided inconsistent data in different PD models. One study showed that PGC1α mRNA was up‐regulated in SH‐SY5Y cells in response to acute MPP + treatment for 24 hours, closely mirroring our result . Torok et al also reported that the PGC1α mRNA levels were increased in the brain of an acute MPTP‐intoxicated mouse model of PD .…”

Section: Discussionsupporting

confidence: 88%

“…PGC1α is a master regulator of mammalian mitochondrial biogenesis in response to disparate physiological or pathological stresses and deemed to be a valuable potential therapeutic target for PD. 9,10 PGC1α plays an indispensable role in normal function of mitochondria, and its deficiency can participate in neurodegenerative processes. On top of that, its overexpression was proven to be neuroprotective against neurotoxins in several models.…”

Section: Decreased Expression Of Pgc1α and Tfam Negatively Correlatmentioning

confidence: 99%

“…PGC1α is a multifunctional coactivator of transcription factors like NRF‐1, NRF‐2, TFAM and FOXO receptors, and thereby regulates mitochondrial biogenesis, respiration as well as function . Moreover, since PGC1α induces the expression of several reactive oxygen species (ROS) detoxifying enzymes including SOD1 and 2, catalase and glutathione peroxidase‐1, it tightly regulates oxidative capacity and reduces oxidative stress . There is a substantial literature indicating possible links between PGC1α and diverse neurodegenerative diseases (NDDs), comprising amyotrophic lateral sclerosis (ALS), Huntington's disease (HD), Alzheimer's disease (AD) and PD .…”

Section: Introductionmentioning

confidence: 99%

“…1,3 Moreover, since PGC1α induces the expression of several reactive oxygen species (ROS) detoxifying enzymes including SOD1 and 2, catalase and glutathione peroxidase-1, it tightly regulates oxidative capacity and reduces oxidative stress. 3,10 There is a substantial literature indicating possible links between PGC1α and diverse neurodegenerative diseases (NDDs), comprising amyotrophic lateral sclerosis (ALS), Huntington's disease (HD), Alzheimer's disease (AD) and PD. 10 As a target gene of PGC1α, TFAM regulates mitochondrial genome replication and transcription as well as mitochondrial biogenesis.…”

Section: Introductionmentioning

confidence: 99%

“…3,10 There is a substantial literature indicating possible links between PGC1α and diverse neurodegenerative diseases (NDDs), comprising amyotrophic lateral sclerosis (ALS), Huntington's disease (HD), Alzheimer's disease (AD) and PD. 10 As a target gene of PGC1α, TFAM regulates mitochondrial genome replication and transcription as well as mitochondrial biogenesis. 11 TFAM also makes a positive contribution to mtDNA stability and initiates synthesis of mtDNA-encoded respiratory chain subunits.…”

Section: Introductionmentioning

confidence: 99%

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Modified level of miR‐376a is associated with Parkinson's disease

Baghi

Delavar

Yadegari

et al. 2020

J Cellular Molecular Medi

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Parkinson's disease (PD) is a frequent progressive neurodegenerative disorder. Impaired mitochondrial function is a major feature of sporadic PD. Some susceptibility or causative genes detected in PD are strongly associated with mitochondrial dysfunction including PGC1α, TFAM and GSK3β. microRNAs (miRNAs) are non‐coding RNAs whose altered levels are proven in disparate PD models and human brains. Therefore, the aim of this study was to detect modulations of miRs upstream of PGC1α, TFAM and GSK3β in association with PD onset and progress. In this study, a total of 33 PD subjects and 25 healthy volunteers were recruited. Candidate miRNA (miR‐376a) was selected through target prediction tools and literature survey. Chronic and acute in vitro PD models were created by MPP+‐intoxicated SHSY5Y cells. The levels of miR‐376a and aforementioned genes were assessed by RT‐qPCR. The expression of target genes was decreased in chronic model while there were dramatically up‐regulated levels of those genes in acute model of PD. miR‐376a was strongly altered in both acute and chronic PD models as well as PBMCs of PD patients. Our results also showed overexpression of PGC1α, and TFAM in PBMCs is inversely correlated with down‐regulation of miR‐376a, suggesting that miR‐376a possibly has an impact on PD pathogenesis through regulation of these genes which are involved in mitochondrial function. miR‐376a expression in PD‐derived PBMCs was also correlated with disease severity and may serve as a potential biomarker for PD diagnosis. This is the first study showing altered levels of miR‐376a in PD models and PBMCs, suggesting the probable role of this miRNA in PD pathogenesis. The present study also proposed TFAM and PGC1α as target genes of miR‐376a for the first time, through which it possibly can exert its impact on PD pathogenesis.

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Section: Discussionsupporting

confidence: 88%

Section: Decreased Expression Of Pgc1α and Tfam Negatively Correlatmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Modified level of miR‐376a is associated with Parkinson's disease

Baghi

Delavar

Yadegari

et al. 2020

J Cellular Molecular Medi

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Propofol induces impairment of mitochondrial biogenesis through inhibiting the expression of peroxisome proliferator–activated receptor‐γ coactivator‐1α

Qin

Wang

2019

J of Cellular Biochemistry

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Propofol is a commonly used general anesthetic in patient care. Recent studies have shown that propofol has neurological side effects especially in young children, which raises a concern regarding the safety of its use. We explored the effects of the molecular mechanism of propofol on neuronal mitochondrial function in SH‐SY5Y cells. Our results demonstrate that clinically relevant doses of propofol reduce the expression of peroxisome proliferator–activated receptor‐γ coactivator‐1α (PGC‐1α) in a dose‐ and time‐dependent manner. At a concentration of 2%, propofol suppresses the mitochondrial regulator nuclear respiratory factor 1 and mitochondrial transcription factor A and impairs neuronal mitochondrial biogenesis. These impairments involve reduction of mitochondrial mass and reduction of the ratio of mitochondrial to nuclear DNA as well as reduction of cytochrome C oxidase activity. Propofol treatment reduces intracellular adenosine triphosphate (ATP) production, the mitochondrial respiratory rate, and increases mitochondrial reactive oxygen species production, implying that it disturbs neuronal mitochondrial function. Overexpression of PGC‐1α rescued propofol‐induced reduced mitochondrial mass, ATP production, and respiratory rate, indicating that PGC‐1α is the mediator of the effect of propofol on mitochondrial function. Finally, we demonstrate that propofol suppresses PGC‐1α by inhibiting cAMP‐response element binding protein (CREB) activation and promoting PKA RI expression, and the addition of cyclic adenosine monophosphate rescues propofol‐mediated reduced PGC‐1α. In conclusion, PGC‐1α is the central mediator of propofol‐induced impairment of mitochondrial biogenesis and neuronal mitochondrial dysfunction. Our study demonstrates the molecular mechanism behind propofol‐induced neurotoxicity and provides valuable information regarding its side effects in clinical practice.

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