2. Academic Validation
  3. Presynaptic Caytaxin prevents apoptosis via deactivating DAPK1 in the acute phase of cerebral ischemic stroke

Presynaptic Caytaxin prevents apoptosis via deactivating DAPK1 in the acute phase of cerebral ischemic stroke

  • Exp Neurol. 2020 Jul;329:113303. doi: 10.1016/j.expneurol.2020.113303.
Shan Wang 1,  Keng Chen 2,  Jia Yu 3,  Xiaojiao Wang 3,  Qiang Li 3,  Fei Lv 4,  Huiyong Shen 5,  Lei Pei 6
Affiliations

Affiliations

  • 1 Department of Biotherapy Center, The Eighth Affiliated Hospital, Sun Yat-Sen University, Shen Zhen 518033, China.
  • 2 Department of Orthopedics, The Eighth Affiliated Hospital, Sun Yat-Sen University, Shenzhen 518033, China.
  • 3 Exchange, Development & Service Center for Science & Technology Talents, The Ministry of Science and Technology (Most), Beijing 100045, China.
  • 4 Department of Emergency, Wuhan Asia Heart Hospital, Wuhan 430033, China.
  • 5 Department of Biotherapy Center, The Eighth Affiliated Hospital, Sun Yat-Sen University, Shen Zhen 518033, China; Department of Orthopedics, The Eighth Affiliated Hospital, Sun Yat-Sen University, Shenzhen 518033, China. Electronic address: shenhuiy@mail.sysu.edu.cn.
  • 6 Department of Neurobiology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China; The Institute for Brain Research (IBR), Huazhong University of Science and Technology, Wuhan 430030, China. Electronic address: peilei@hust.edu.cn.
PMID: 32277960 DOI: 10.1016/j.expneurol.2020.113303
Abstract

Death-associated protein kinase 1 (DAPK1) is a key protein that mediates neuronal death in ischemic stroke. Although the substrates of DAPK1 and molecular signal in stroke have been gradually discovered, the modulation of DAPK1 itself is still unclear. Here we first reveal that Caytaxin, a brain-specific member of BCL2/adenovirus E1B -interacting protein (BNIP-2), increases and interacts with DAPK1 as early as 2 h after middle cerebral artery occlusion (MCAO) in the penumbra area of mouse brain. Furthermore, Caytaxin binds to DAPK1 at the presynaptic site and inhibits DAPK1 catalytic activity. Silencing Caytaxin by Caytaxin shRNA (Sh-Caytaxin) enhances DAPK1 activity, deteriorates neuronal Apoptosis and brain injuries both in vivo and in vitro. Thus, elevating presynaptic Caytaxin could prevent neuronal Apoptosis by inhibiting DAPK1 activation in the acute stage of ischemic stroke. Caytaxin may physiologically protect neuronal cells and represent a potential prevention and therapeutic target in the early phase of cerebral ischemic stroke.

Keywords

Catalytic activity; Caytaxin; Cerebral ischemic stroke; DAPK1; Neuronal death.

Figures
Products
  • Cat. No.
    Product Name
    Description
    Target
    Research Area
  • HY-15513
    98.26%, DAPK Inhibitor