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Intermittent hypoxia protects cerebral mitochondrial function from calcium overload

Abstract

Hypoxia leads to Ca2+ overload and results in mitochondrial uncoupling, decreased ATP synthesis, and neuronal death. Inhibition of mitochondrial Ca2+ overload protects mitochondrial function after hypoxia. The present study was aimed to investigate the effect of intermittent hypoxia on mitochondrial function and mitochondrial tolerance to Ca2+ overload. Wistar rats were divided into control and intermittent hypoxia (IH) groups. The IH group was subject to hypoxia for 4 h daily in a hypobaric cabin (5,000 m) for 7 days. Brain mitochondria were isolated on day 7 following hypoxia. The baseline mitochondrial functions, such as ST3, ST4, and respiratory control ratio (RCR = ST3/ST4), were measured using a Clark-type oxygen electrode. Mitochondrial adenine nucleotide concentrations were measured by HPLC. Mitochondrial membrane potential was determined by measuring rhodamine 123 (Rh-123) fluorescence in the absence and presence of high Ca2+ concentration (0.1 M), which simulates Ca2+ overload. Our results revealed that IH did not affect mitochondrial respiratory functions, but led to a reduction in AMP and an increase in ADP concentrations in mitochondria. Both control and IH groups demonstrated decreased mitochondrial membrane potential in the presence of high Ca2+ (0.1 M), while the IH group showed a relative higher mitochondrial membrane potential. These results indicated that the neuroprotective effect of intermittent hypoxia was resulted partly from preserving mitochondrial membrane potential, and increasing mitochondrial tolerance to high calcium levels. The increased ADP and decreased AMP in mitochondria following intermittent hypoxia may be a mechanism underlying this protection.

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Acknowledgments

This work was supported by grants from the National Natural Science Foundation of China (grant number 81055828) and the Major State Basic Research Development Program of China (Grant number 2012CB518201).

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Correspondence to Yuqi Gao.

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Chen, J., Liao, W., Gao, W. et al. Intermittent hypoxia protects cerebral mitochondrial function from calcium overload. Acta Neurol Belg 113, 507–513 (2013). https://doi.org/10.1007/s13760-013-0220-8

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  • DOI: https://doi.org/10.1007/s13760-013-0220-8

Keywords

  • Intermittent hypoxia
  • Mitochondria
  • Calcium
  • Mitochondrial membrane potential
  • Respiratory control rate