1. Academic Validation
  2. DUSP14 rescues cerebral ischemia/reperfusion (IR) injury by reducing inflammation and apoptosis via the activation of Nrf-2

DUSP14 rescues cerebral ischemia/reperfusion (IR) injury by reducing inflammation and apoptosis via the activation of Nrf-2

  • Biochem Biophys Res Commun. 2019 Feb 12;509(3):713-721. doi: 10.1016/j.bbrc.2018.12.170.
Song Jianrong 1 Zhao Yanjun 2 Yu Chen 2 Xu Jianwen 3
Affiliations

Affiliations

  • 1 Department of Neurosurgery, Baoji Municipal Central Hospital, Baoji City, 721008, China.
  • 2 Department of Anesthesiology, Beijing Tsinghua Changgung Hospital, No. 168, Li Tang Road, Changping District, Beijing 102218, China.
  • 3 Department of Anesthesiology, Zaozhuang Municipal Hospital, Zaozhuang, Shandong 277100, China. Electronic address: [email protected].
Abstract

Ischemic stroke is the second most common cause of death, a major cause of acquired disability in adults. However, the pathogenesis that contributes to ischemic stroke has not been fully understood. Dual-specificity Phosphatase 14 (DUSP14, also known as MKP6) is a MAP kinase Phosphatase, playing important role in regulating various cellular processes, including oxidative stress and inflammation. However, its effects on cerebral ischemia/reperfusion (IR) are unclear. In the study, we found that DUSP14 expression was decreased responding to IR surgery. Over-expressing DUSP14 reduced the infarction volume of cerebral IR mice. Cognitive dysfunction was also improved in mice with DUSP14 over-expression. Promoting DUSP14 expression markedly reduced the activation of glial cells, as evidenced by the decreases in GFAP and Iba-1 expressions in mice with cerebral IR injury. In addition, inflammatory response induced by cerebral IR injury was inhibited in DUSP14 over-expressed mice, as proved by the reduced expression of tumor necrosis factor (TNF)-α and interleukin 1β (IL-1β). Furthermore, oxidative stress was markedly reduced by DUSP14 over-expression through elevating nuclear factor-erythroid 2 related factor 2 (Nrf-2) signaling pathway. Importantly, we found that DUSP14 could interact with Nrf-1, which thereby protected mice against cerebral IR injury. In vitro, we also found that repressing Nrf-2 expression abrogated DUSP14 over-expression-reduced inflammation and ROS generation. Consistent with the anti-inflammatory effect of DUSP14, reducing the production of Reactive Oxygen Species (ROS) also down-regulated TNF-α and IL-1β expressions. Collectively, elevated DUSP14 alleviated brain damage from cerebral IR injury through Nrf-2-regulated anti-oxidant signaling pathway, and the restraining of inflammatory response. These results suggested that DUSP14 might be a potential therapeutic target to prevent ischemic stroke.

Keywords

Cerebral IR injury; DUSP14; Inflammation; Nrf-2; Oxidative stress.

Figures
Products