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Suppression of Inner Mitochondrial Membrane Peptidase 2-Like (IMMP2L) Gene Exacerbates Hypoxia-Induced Neural Death Under High Glucose Condition

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Abstract

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.

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Acknowledgements

This study was supported by National Natural Science Foundation of China (Grant Nos. 81360196, 81660229) and Study Abroad Returnees Science Foundation of Ningxia Province (Grant No. 20146).

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Authors and Affiliations

  1. Department of Pathology, Ningxia Key Laboratory of Cerebrocranial Diseases, Incubation Base of National Key Laboratory, Ningxia Medical University, Yinchuan, 750004, Ningxia, China

    Yi Ma & Jianzhong Zhang

  2. Department of Pharmaceutical Sciences, Biomanufacturing Research Institute and Technological Enterprise (BRITE), North Carolina Central University, Durham, NC, 27707, USA

    P. Andy Li

  3. Department of Anesthesiology, General Hospital, Ningxia Medical University, Yinchuan, 750004, Ningxia, China

    Zijing Zhang, Nina Ma & Xinli Ni

  4. Department of Orthopedics, General Hospital, Ningxia Medical University, Yinchuan, 750004, Ningxia, China

    Zhirong Chen

  5. Department of Biology and Genetics, Ningxia Medical University, Yinchuan, 750004, Ningxia, China

    Jingwen Zhang

  6. Department of Neurology, Tangdu Hospital, The Fourth Military Medical University, Xi’an, 710038, Shanxi, China

    Shihui Sun

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  1. Yi Ma
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  2. Zijing Zhang
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  3. Zhirong Chen
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  4. Nina Ma
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Correspondence to Jianzhong Zhang.

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Yi Ma and Zijing Zhang contributed equally to this study, they are co-first authors.

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Ma, Y., Zhang, Z., Chen, Z. et al. Suppression of Inner Mitochondrial Membrane Peptidase 2-Like (IMMP2L) Gene Exacerbates Hypoxia-Induced Neural Death Under High Glucose Condition. Neurochem Res 42, 1504–1514 (2017). https://doi.org/10.1007/s11064-017-2207-y

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  • DOI: https://doi.org/10.1007/s11064-017-2207-y

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