Abstract
Serum response factor (SRF), a transcription factor highly expressed in neurons, is involved in neuronal survival and the pathogenesis of some neurodegenerative disorders. The ablation of SRF renders the midbrain dopaminergic (DA) neurons vulnerable to 1-methyl 4-phenyl 1,2,3,6-tetrahydropyridine-induced neurotoxicity, however, the underlying mechanisms remain poorly understood. Here, we report decreased SRF levels in the substantia nigra (SN) of rotenone-treated rats that was associated with the loss of tyrosine hydroxylase (TH)-positive neurons. SRF expression was also reduced in rotenone-treated PC12 cells in vitro. In addition, Srf knockdown augmented rotenone-induced toxicity in PC12 cells. In contrast, overexpression of Srf attenuated the cells’ sensitivity to rotenone and alleviated rotenone-induced α-synuclein accumulation. The protective effect of SRF was abolished when the expression of autophagy-related proteins Beclin 1 and Atg5 was suppressed. These results suggested that SRF may promote DA neuron survival by regulating autophagy, and thus serves as a critical molecule in PD progression.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 288-295 |
| Number of pages | 8 |
| Journal | Neuroscience |
| Volume | 371 |
| DOIs | |
| State | Published - Feb 10 2018 |
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Keywords
- autophagy
- Beclin 1
- dopaminergic neuron
- Parkinson's disease
- serum response factor
ASJC Scopus subject areas
- Neuroscience(all)
Cite this
Serum Response Factor Promotes Dopaminergic Neuron Survival via Activation of Beclin 1-Dependent Autophagy. / Cheng, Xiao Yu; Li, Si Yue; Mao, Cheng Jie; Wang, Mei Xia; Chen, Jing; Wang, Fen; Wang, Guang Hui; Deng, Wenbin; Li, Xiao Kang; Liu, Chun Feng.
In: Neuroscience, Vol. 371, 10.02.2018, p. 288-295.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Serum Response Factor Promotes Dopaminergic Neuron Survival via Activation of Beclin 1-Dependent Autophagy
AU - Cheng, Xiao Yu
AU - Li, Si Yue
AU - Mao, Cheng Jie
AU - Wang, Mei Xia
AU - Chen, Jing
AU - Wang, Fen
AU - Wang, Guang Hui
AU - Deng, Wenbin
AU - Li, Xiao Kang
AU - Liu, Chun Feng
PY - 2018/2/10
Y1 - 2018/2/10
N2 - Serum response factor (SRF), a transcription factor highly expressed in neurons, is involved in neuronal survival and the pathogenesis of some neurodegenerative disorders. The ablation of SRF renders the midbrain dopaminergic (DA) neurons vulnerable to 1-methyl 4-phenyl 1,2,3,6-tetrahydropyridine-induced neurotoxicity, however, the underlying mechanisms remain poorly understood. Here, we report decreased SRF levels in the substantia nigra (SN) of rotenone-treated rats that was associated with the loss of tyrosine hydroxylase (TH)-positive neurons. SRF expression was also reduced in rotenone-treated PC12 cells in vitro. In addition, Srf knockdown augmented rotenone-induced toxicity in PC12 cells. In contrast, overexpression of Srf attenuated the cells’ sensitivity to rotenone and alleviated rotenone-induced α-synuclein accumulation. The protective effect of SRF was abolished when the expression of autophagy-related proteins Beclin 1 and Atg5 was suppressed. These results suggested that SRF may promote DA neuron survival by regulating autophagy, and thus serves as a critical molecule in PD progression.
AB - Serum response factor (SRF), a transcription factor highly expressed in neurons, is involved in neuronal survival and the pathogenesis of some neurodegenerative disorders. The ablation of SRF renders the midbrain dopaminergic (DA) neurons vulnerable to 1-methyl 4-phenyl 1,2,3,6-tetrahydropyridine-induced neurotoxicity, however, the underlying mechanisms remain poorly understood. Here, we report decreased SRF levels in the substantia nigra (SN) of rotenone-treated rats that was associated with the loss of tyrosine hydroxylase (TH)-positive neurons. SRF expression was also reduced in rotenone-treated PC12 cells in vitro. In addition, Srf knockdown augmented rotenone-induced toxicity in PC12 cells. In contrast, overexpression of Srf attenuated the cells’ sensitivity to rotenone and alleviated rotenone-induced α-synuclein accumulation. The protective effect of SRF was abolished when the expression of autophagy-related proteins Beclin 1 and Atg5 was suppressed. These results suggested that SRF may promote DA neuron survival by regulating autophagy, and thus serves as a critical molecule in PD progression.
KW - autophagy
KW - Beclin 1
KW - dopaminergic neuron
KW - Parkinson's disease
KW - serum response factor
UR - http://www.scopus.com/inward/record.url?scp=85039854363&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85039854363&partnerID=8YFLogxK
U2 - 10.1016/j.neuroscience.2017.11.040
DO - 10.1016/j.neuroscience.2017.11.040
M3 - Article
C2 - 29196028
AN - SCOPUS:85039854363
VL - 371
SP - 288
EP - 295
JO - Neuroscience
JF - Neuroscience
SN - 0306-4522
ER -