1. Academic Validation
  2. Deficiency of unc-51 like kinase 1 (Ulk1) protects against mice traumatic brain injury (TBI) by suppression of p38 and JNK pathway

Deficiency of unc-51 like kinase 1 (Ulk1) protects against mice traumatic brain injury (TBI) by suppression of p38 and JNK pathway

  • Biochem Biophys Res Commun. 2018 Sep 5;503(2):467-473. doi: 10.1016/j.bbrc.2018.04.154.
Hao-Lan Wei 1 Su-Qing Ma 2 Chun-Xia Li 3
Affiliations

Affiliations

  • 1 Department of Pediatrics, Liaocheng People's Hospital, Liaocheng, Shandong 252000, China.
  • 2 Department of Pediatrics, Shandong Shenxian Second People's Hospital, Liaocheng, Shandong 252423, China.
  • 3 Department of Pediatrics, Liaocheng People's Hospital, Liaocheng, Shandong 252000, China. Electronic address: lcyiyuan@126.com.
Abstract

Unc-51 like Autophagy activating kinase 1 (ULK1) is a serine/threonine kinase that plays a key role in regulating Autophagy processes. We attempted to investigate the effects of ULK1 on traumatic brain injury (TBI) progression by using wild type (WT) mice and Ulk1-knockout (KO) mice suffered with or not TBI. The results were verified using LPS-treated primary astrocyte (AST). Here, ULK1 was over-expressed in hippocampus of WT mice after TBI, as well as in lipopolysaccharide (LPS)-stimulated AST. Ulk1-deletion improved cognitive ability and hippocampus histological changes in TBI mice. Nissl and neuronal nuclei (NeuN) staining indicated that Ulk1-deletion increased the number of surviving neurons in hippocampus of TBI mice. Ulk1-ablation alleviated neuroinflammation, as evidenced by the reduced expression of hippocampus pro-inflammatory cytokines in TBI mice. TBI-induced Apoptosis was also ameliorated by Ulk1-ablation, as proved by the reduced number of TUNEL-staining cells, and cleaved Caspase-3 and poly (ADP-ribose) polymerase (PARP) expressions. Moreover, Ulk1-knockout suppressed TBI-stimulated activation of astrocytes and microglia cells. Additionally, hippocampus Autophagy induced by TBI was attenuated by Ulk1-knockout. Further, TBI-activated p38/c-Jun N-terminal Kinase (JNK) pathway was repressed by Ulk1-deletion in hippocampus of mice. The findings above were confirmed in LPS-stimulated AST with or without ULK1 siRNA transfection. Intriguingly, pre-treatment of p38 or JNK Activator markedly abolished the anti-inflammation, anti-apoptosis and anti-autophagy effects of Ulk1-knockdown on LPS-incubated AST. In conclusion, our results demonstrated that ULK1 might be a potential target for developing therapeutic strategy against TBI in future.

Keywords

Apoptosis and autophagy; Inflammation; Traumatic brain injury (TBI); Ulk1; p38/JNK.

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