Ya Wen1,2,3, Xiangjian Zhang1,2,3, Xiaoyun Liu1,2, Yinghao Huo1,2, Yuxiao Gao1,2,3, Yi Yang1,2,3. 1. Department of Neurology, The Second Hospital of Hebei Medical University Shijiazhuang 050000, Hebei, P. R. China. 2. Hebei Key Laboratory of Neurology Shijiazhuang 050000, Hebei, P. R. China. 3. Hebei Key Laboratory of Vascular Homeostasis Shijiazhuang 050000, Hebei, P. R. China.
Abstract
BACKGROUND: Cerebral ischemia/reperfusion (I/R) injury is a severe complication during the treatment of patients with stroke. It has been shown that the expression of SNHG15 was increased in patients with ischemic stroke (IS). However, the function and regulatory mechanism of SNHG15 in IS remains unclear. METHODS: An oxygen glucose deprivation/reoxygenation (OGD/R) cell model was use to establish an in vitro model of I/R injury. RT-qPCR assay was used to detect the level of SNHG15 in OGD/R-treated SH-SY5Y cells. Meanwhile, middle cerebral artery occlusion (MCAO) was used to establish an in vivo model of cerebral I/R injury. RESULTS: The expression of SNHG15 was upregulated in OGD/R-treated SH-SY5Y cells. Downregulation of SNHG15 during reperfusion reduced cell death in OGD/R-treated SH-SY5Y cells. In addition, SNHG15 knockdown suppressed OGD/R-induced apoptosis in SY-SY5Y cells by attenuating intracellular ROS generation and reducing mitochondrial membrane potential (MMP) lost. In addition, SNHG15 knockdown promoted cell cycle transition in SY-SY5Y cells after OGD/R insult accompany with PI3K/Akt signaling activation. Meanwhile, mechanism investigations suggested SNHG15 knockdown downregulated the expression of FOXO1 through acting as a competitive 'sponge' of miR-183-5p. Most importantly, knockdown of SNHG15 expression in vivo inhibited neuronal apoptosis and decreased infarct area in MCAO rats. CONCLUSION: Thus, the present study indicated that SNHG15 knockdown protected against cerebral I/R injury via targeting miR-183-5p/FOXO1 axis, which may represent a potential therapeutic option for the treatment of cerebral IS. AJTR
BACKGROUND:Cerebral ischemia/reperfusion (I/R) injury is a severe complication during the treatment of patients with stroke. It has been shown that the expression of SNHG15 was increased in patients with ischemic stroke (IS). However, the function and regulatory mechanism of SNHG15 in IS remains unclear. METHODS: An oxygen glucose deprivation/reoxygenation (OGD/R) cell model was use to establish an in vitro model of I/R injury. RT-qPCR assay was used to detect the level of SNHG15 in OGD/R-treated SH-SY5Y cells. Meanwhile, middle cerebral artery occlusion (MCAO) was used to establish an in vivo model of cerebral I/R injury. RESULTS: The expression of SNHG15 was upregulated in OGD/R-treated SH-SY5Y cells. Downregulation of SNHG15 during reperfusion reduced cell death in OGD/R-treated SH-SY5Y cells. In addition, SNHG15 knockdown suppressed OGD/R-induced apoptosis in SY-SY5Y cells by attenuating intracellular ROS generation and reducing mitochondrial membrane potential (MMP) lost. In addition, SNHG15 knockdown promoted cell cycle transition in SY-SY5Y cells after OGD/R insult accompany with PI3K/Akt signaling activation. Meanwhile, mechanism investigations suggested SNHG15 knockdown downregulated the expression of FOXO1 through acting as a competitive 'sponge' of miR-183-5p. Most importantly, knockdown of SNHG15 expression in vivo inhibited neuronal apoptosis and decreased infarct area in MCAOrats. CONCLUSION: Thus, the present study indicated that SNHG15 knockdown protected against cerebral I/R injury via targeting miR-183-5p/FOXO1 axis, which may represent a potential therapeutic option for the treatment of cerebral IS. AJTR
Authors: Samuel Gebremedhn; Dessie Salilew-Wondim; Michael Hoelker; Franca Rings; Christiane Neuhoff; Ernst Tholen; Karl Schellander; Dawit Tesfaye Journal: Biol Reprod Date: 2016-04-27 Impact factor: 4.285