TRPC1 deletion causes striatal neuronal cell apoptosis and proteomic alterations in mice

Dian Wang, Haitao Yu, Benhong Xu, Hua Xu, Zaijun Zhang, Xiaohu Ren, Jianhui Yuan, Jianjun Liu, Yi Guo, Peter Spencer, Xifei Yang

Research output: Contribution to journalArticle

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Abstract

Transient receptor potential channel 1 (TRPC1) is widely expressed throughout the nervous system, while its biological role remains unclear. In this study, we showed that TRPC1 deletion caused striatal neuronal loss and significantly increased TUNEL-positive and 8-hydroxy-2'-deoxyguanosine (8-OHdG) staining in the striatum. Proteomic analysis by two-dimensional fluorescence difference gel electrophoresis (2D-DIGE) coupled with mass spectrometry (MS) revealed a total of 51 differentially expressed proteins (26 increased and 25 decreased) in the stratum of TRPC1 knockout (TRPC1-/-) mice compared to that of wild type (WT) mice. Bioinformatics analysis showed these dysregulated proteins included: oxidative stress-related proteins, synaptic proteins, endoplasmic reticulum (ER) stress-related proteins and apoptosis-related proteins. STRING analysis showed these differential proteins have a well-established interaction network. Based on the proteomic data, we revealed by Western-blot analysis that TRPC1 deletion caused ER stress as evidenced by the dysregulation of GRP78 and PERK activation-related signaling pathway, and elevated oxidative stress as suggested by increased 8-OHdG staining, increased NADH dehydrogenase (ubiquinone) flavoprotein 2 (NDUV2) and decreased protein deglycase (DJ-1), two oxidative stress-related proteins. In addition, we also demonstrated that TRPC1 deletion led to significantly increased apoptosis in striatum with concurrent decrease in both 14-3-3Z and dynamin-1 (D2 dopamine (DA) receptor binding), two apoptosis-related proteins. Taken together, we concluded that TRPC1 deletion might cause striatal neuronal apoptosis by disturbing multiple biological processes (i.e., ER stress, oxidative stress and apoptosis-related signaling). These data suggest that TRPC1 may be a key player in the regulation of striatal cellular survival and death.

Original languageEnglish (US)
Article number72
JournalFrontiers in Aging Neuroscience
Volume10
Issue numberMAR
DOIs
StatePublished - Mar 20 2018

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Transient Receptor Potential Channels
Corpus Striatum
Proteomics
Apoptosis
Endoplasmic Reticulum Stress
Oxidative Stress
Heat-Shock Proteins
Two-Dimensional Difference Gel Electrophoresis
Proteins
Dynamin I
Staining and Labeling
Electron Transport Complex I
Biological Phenomena
Flavoproteins
Dopamine D2 Receptors
In Situ Nick-End Labeling
Computational Biology
Knockout Mice
Nervous System
Mass Spectrometry

Keywords

  • Apoptosis
  • ER stress response
  • Proteomics
  • Striatum
  • TRPC1 deletion

ASJC Scopus subject areas

  • Aging
  • Cognitive Neuroscience

Cite this

TRPC1 deletion causes striatal neuronal cell apoptosis and proteomic alterations in mice. / Wang, Dian; Yu, Haitao; Xu, Benhong; Xu, Hua; Zhang, Zaijun; Ren, Xiaohu; Yuan, Jianhui; Liu, Jianjun; Guo, Yi; Spencer, Peter; Yang, Xifei.

In: Frontiers in Aging Neuroscience, Vol. 10, No. MAR, 72, 20.03.2018.

Research output: Contribution to journalArticle

Wang, D, Yu, H, Xu, B, Xu, H, Zhang, Z, Ren, X, Yuan, J, Liu, J, Guo, Y, Spencer, P & Yang, X 2018, 'TRPC1 deletion causes striatal neuronal cell apoptosis and proteomic alterations in mice', Frontiers in Aging Neuroscience, vol. 10, no. MAR, 72. https://doi.org/10.3389/fnagi.2018.00072
Wang, Dian ; Yu, Haitao ; Xu, Benhong ; Xu, Hua ; Zhang, Zaijun ; Ren, Xiaohu ; Yuan, Jianhui ; Liu, Jianjun ; Guo, Yi ; Spencer, Peter ; Yang, Xifei. / TRPC1 deletion causes striatal neuronal cell apoptosis and proteomic alterations in mice. In: Frontiers in Aging Neuroscience. 2018 ; Vol. 10, No. MAR.
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AU - Yuan, Jianhui

AU - Liu, Jianjun

AU - Guo, Yi

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