Suppression of Inner Mitochondrial Membrane Peptidase 2-Like (IMMP2L) Gene Exacerbates Hypoxia-Induced Neural Death Under High Glucose Condition.
It is known that diabetes hyperglycemia enhances cerebral ischemia and reperfusion induced damage. We have previously shown that mutation of inner mitochondrial membrane peptidase 2-like (IMMP2L) increases brain damage caused by transient cerebral ischemia. In this study, we attempt to examine the impact of IMMP2L deficiency on an in vitro model that mimics the diabetic hypoxic conditions. Normal IMMP2L wild type and IMMP2L gene deleted HT22 cells were cultured. Hypoxia was induced under high glucose and acidic conditions with 4 h of oxygen deprivation. Cell viability was assessed by CCK-8 assay and cell death was determined using Annexin V/7-AAD assay. Superoxide production was measured using dihydroethidium staining and mitochondrial membrane potential was detected using JC-1 probe. Suppression of IMMP2L reduced the cell viability, increased the ROS production and decreased the mitochondrial membrane potential. In conclusion, our study demonstrated that deficiency of IMMP2L in cells, cultured under hypoxia, high glucose and acidic conditions, exacerbated neuronal death under a condition that mimics in vivo cerebral ischemia in diabetic condition.
Department of Pathology, Ningxia Key Laboratory of Cerebrocranial Diseases, Incubation Base of National Key Laboratory, Ningxia Medical University, Yinchuan, 750004, Ningxia, China.
Yi
Y
Ma
Department of Anesthesiology, General Hospital, Ningxia Medical University, Yinchuan, 750004, Ningxia, China.
Zijing
Z
Zhang
Department of Orthopedics, General Hospital, Ningxia Medical University, Yinchuan, 750004, Ningxia, China.
Zhirong
Z
Chen
Department of Anesthesiology, General Hospital, Ningxia Medical University, Yinchuan, 750004, Ningxia, China.
Nina
N
Ma
Department of Neurology, Tangdu Hospital, The Fourth Military Medical University, Xi'an, 710038, Shanxi, China.
Shihui
S
Sun
Department of Biology and Genetics, Ningxia Medical University, Yinchuan, 750004, Ningxia, China.
Jingwen
J
Zhang
Department of Anesthesiology, General Hospital, Ningxia Medical University, Yinchuan, 750004, Ningxia, China.
Xinli
X
Ni
Department of Pathology, Ningxia Key Laboratory of Cerebrocranial Diseases, Incubation Base of National Key Laboratory, Ningxia Medical University, Yinchuan, 750004, Ningxia, China. zhangjz@nxmu.edu.cn.
Jianzhong
J
Zhang
Department of Pharmaceutical Sciences, Biomanufacturing Research Institute and Technological Enterprise (BRITE), North Carolina Central University, Durham, NC, 27707, USA.
P Andy
PA
Li
D000818:Animals; D016923:Cell Death / Q000187:drug effects / Q000502:physiology; D015687:Cell Hypoxia / Q000187:drug effects / Q000502:physiology; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D010450:Endopeptidases / Q000172:deficiency* / Q000235:genetics; D005947:Glucose / Q000008:administration & dosage / Q000633:toxicity*; D057809:HEK293 Cells; D006801:Humans; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects / Q000502:physiology; D051379:Mice; D051336:Mitochondrial Membranes / Q000187:drug effects / Q000378:metabolism*; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*
D010450:Endopeptidases; C425070:IMMP2L protein, human; D005947:Glucose
Cerebral ischemia/reperfusion injury; Diabetes; IMMP2L