Mdivi-1 prevents apoptosis induced by ischemia-reperfusion injury in primary hippocampal cells via inhibition of reactive oxygen species-activated mitochondrial pathway.
Apoptosis is one of the major mechanisms of neuronal injury during ischemic-reperfusion (I/R). Mitochondrial division inhibitor (mdivi-1) is a selective inhibitor of mitochondrial fission protein Drp1. The previous experiments support that mdivi-1 reduce I/R injury in the heart model of rat, but the neuroprotective effect of the mdivi-1 is not yet clearly defined at the cellular levels in brain. In our present study, we estimated a brain model of I/R injury in vitro by subjecting oxygen and glucose deprivation (OGD) followed by reoxygenation to the cultured rat primary hippocampal cells, which aimed to find the neuroprotective mechanism of mdivi-1. The cell was pretreated with mdivi-1 for 40 minutes and then ischemia for 6 hours followed by reperfusion for 20 hours. The redox state, cell apoptosis, and expression of Drp1, Bcl-2, Bax, and cytochrome C proteins were measured. The data showed that administration of mdivi-1 at the doses of 50 μM significantly reduced oxidative stress, attenuated cell apoptosis, upregulated Bcl-2 expression, and downregulated Drp1, Bax, and cytochrome C expression. The results suggested that mdivi-1 protected brain from OGD reperfusion injury, which through suppressing the ROS initiated mitochondrial pathway.
Medical College of Qingdao University, Qingdao, Shandong Province, China.
Jinying
J
Wang
Department of Anesthesiology, Affiliated Hospital of Qingdao University, Wutaishanlu, Huangdao, Qingdao, Shandong Province, China.
Peng
P
Wang
Department of Anesthesiology, Affiliated Hospital of Qingdao University, Wutaishanlu, Huangdao, Qingdao, Shandong Province, China.
Shuhong
S
Li
Department of Anesthesiology, Affiliated Hospital of Qingdao University, Wutaishanlu, Huangdao, Qingdao, Shandong Province, China. Electronic address: wshlei@aliyun.com.
Shilei
S
Wang
Department of Anesthesiology, Affiliated Hospital of Qingdao University, Wutaishanlu, Huangdao, Qingdao, Shandong Province, China.
Yu
Y
Li
Medical College of Qingdao University, Qingdao, Shandong Province, China.
Nan
N
Liang
Medical College of Qingdao University, Qingdao, Shandong Province, China.
Min
M
Wang
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D002478:Cells, Cultured; D045304:Cytochromes c / Q000378:metabolism; D034281:Dynamins / Q000378:metabolism; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D018696:Neuroprotective Agents / Q000494:pharmacology* / Q000627:therapeutic use; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D052999:Quinazolinones / Q000494:pharmacology* / Q000627:therapeutic use; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism*; D015427:Reperfusion Injury / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D051028:bcl-2-Associated X Protein / Q000378:metabolism
C549041:3-(2,4-dichloro-5-methoxyphenyl)-2-sulfanyl-4(3H)-quinazolinone; D018696:Neuroprotective Agents; D019253:Proto-Oncogene Proteins c-bcl-2; D052999:Quinazolinones; D017382:Reactive Oxygen Species; D051028:bcl-2-Associated X Protein; D045304:Cytochromes c; C519851:Dnm1l protein, rat; D034281:Dynamins
Ischemia–reperfusion injury; apoptosis; mitochondrial fission; oxidative stress