1. Academic Validation
  2. Neuroprotective Effects of CGP3466B on Apoptosis Are Modulated by Protein-L-isoaspartate (D-aspartate) O-methyltransferase/Mst1 Pathways after Traumatic Brain Injury in Rats

Neuroprotective Effects of CGP3466B on Apoptosis Are Modulated by Protein-L-isoaspartate (D-aspartate) O-methyltransferase/Mst1 Pathways after Traumatic Brain Injury in Rats

  • Sci Rep. 2017 Aug 23;7(1):9201. doi: 10.1038/s41598-017-08196-3.
Feng Liang 1 Ligen Shi 1 Jingwei Zheng 1 Sheng Chen 1 Yangxin Wang 2 Jianmin Zhang 3
Affiliations

Affiliations

  • 1 Department of Neurosurgery, Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, 310009, China.
  • 2 Department of Orthopaedics, Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, 310009, China.
  • 3 Department of Neurosurgery, Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, 310009, China. zjm135@vip.sina.com.
Abstract

Neuronal Apoptosis chiefly contributes to the cell loss following traumatic brain injury (TBI). CGP3466B is a compound related to the anti-Parkinsonism drug R-(-)-deprenyl. Previous studies have illuminated anti-apoptosis effects of CGP3466B in different cell lines, but the underlying mechanisms have not been fully elucidated. Mammalian sterile 20 (STE20)-like kinase1 (Mst1) is a core component of the Hippo signaling pathway. Protein-L-isoaspartate (D-aspartate) O-methyltransferase (PCMT1) is an Enzyme that repairs damaged L-isoaspartyl residues in proteins. The present study was performed to investigate the neuroprotective effects of CGP3466B and to determine a potential PCMT1/Mst1 neuronal anti-apoptotic pathway after TBI. Double immunofluorescence staining demonstrated that PCMT1 and Mst1 are co-located in neurons. Administration of CGP3466B improved neurological function, downregulated the ROS level and alleviated brain edema at 24 h after TBI. CGP3466B alleviates neuronal Apoptosis by increasing PCMT1 expression and subsequently inhibiting MST1 activation, resulting in changing the expression levels of Bax, Bcl-2 and active-caspase3. The TUNEL staining results also support the anti-apoptosis effects of CGP3466B. The anti-apoptotic effects of CGP3466B were abolished by chelerythrine, an Mst1 activator, without changing PCMT1 levels. In conclusion, our findings suggest CGP3466B may have a promising therapeutic potential by modulating PCMT1/Mst1 signaling pathway after TBI injury.

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