Portal de Periódicos da CAPES

Targeting cyclophilin-D by compound 19 protects neuronal cells from oxygen glucose deprivation/re-oxygenation

2017; Impact Journals LLC; Volume: 8; Issue: 52 Linguagem: Inglês

10.18632/oncotarget.21655

1949-2553

Jinyu Zheng, Enhui Cui, Haikou Yang, Li Mao, Jing Zhou, Ming Yan, Jian Sun, Derong Tang,

Pancreatic function and diabetes

// Jinyu Zheng 1, * , Enhui Cui 2, * , Haikou Yang 2 , Mao Li 2 , Jing Zhou 2 , Ming Yan 2 , Jian Sun 2 and De-Rong Tang 3 1 Department of Neurosurgery, The Affiliated Huai'an Hospital of Xuzhou Medical College, Huai'an, China 2 Department of Anesthesiology, Huai'an Maternity and Child Healthcare Hospital, Yangzhou University Medical School, Huai'an, China 3 Department of Thoracic Surgery, Huai'an First People's Hospital, Nanjing Medical University, Huai'an, China * Co-first authors Correspondence to: Jian Sun, email: sunjianmzys@163.com De-Rong Tang, email: tangderonglw@163.com Keywords: oxygen glucose deprivation/re-oxygenation, cyclophilin-D, compound 19, programmed necrosis, P53 Received: July 25, 2017 Accepted: August 28, 2017 Published: October 06, 2017 ABSTRACT Oxygen and glucose deprivation (OGD) with re-oxygenation (OGDR) is applied to neuronal cells to mimic ischemia-reperfusion injuries. Activation of cyclophilin D (Cyp-D)-dependent programmed necrosis pathway mediates OGDR-induced neuronal cell damages. Here, we tested the potential effect of Compound 19 (C19), a novel Cyp-D inhibitor, in this process. In both established neuronal cell lines (Neuro-2a and NB41A3 cells) and the primary murine CA1 hippocampal neurons, pretreatment with C19 largely attenuated OGDR-induced cell viability reduction and cell death. Significantly, C19 was ineffective in Cyp-D-silenced Neuro-2a cells. OGDR induced mitochondria-dependent programmed necrosis in neuronal cells. OGDR induced p53 translocation to mitochondria and association with Cyp-D, causing mitochondrial depolarization, cytochrome C release and reactive oxygen species production. Such effects were largely attenuated with pre-treatment of C19. Importantly, C19 was significantly more efficient than other known Cyp-D inhibitors in protecting neuronal cells from OGDR. These results suggest that targeting Cyp-D by C19 protects neuronal cells from OGDR.