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Isola 2022 Abstract Bioblast

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P12.
Isola Raffaella
Isola Raffaella, Noli R, Isola M, Crisafulli A, Vargiu R, Loy F, Lai Y (2022) In rat brain and heart acute hypoxia induced mild changes in OXPHOS in both sexes.
Bioblast 2022: BEC Inaugural Conference. In: https://doi.org/10.26124/bec:2022-0001

Link: Bioblast 2022: BEC Inaugural Conference

Isola Raffaella, Noli R, Isola M, Crisafulli A, Vargiu R, Loy F, Lai Y (2022)

Event: Bioblast 2022

Acutely exposure to low oxygen concentrations, impairs the capability to perform muscular workout. On the other hand, repeated and prolonged exposure to low PO2 may improve physical performance due to a progressive adaptation of the body. This is mainly due to enhanced hemoglobin and red blood cells content, and decreased sympathetic autonomic nervous system input. These changes were evaluated in a number of chronic hypoxia studies [1-2], whereas acute hypoxia outcomes are still unknown.

This study investigates on acute hypoxia and normoxia impact on cardiac and brain mitochondrial bioenergetics and the possible occurrence of different gender responses.

We used male and female Wistar rats that had been trained for 5 weeks, 1h/day, on a treadmill set at 35 cm/s. The day of the experiment they were allowed to run on the treadmill for 30 minutes in hypoxia (at the same oxygen concentration of an altitude of 4000 mt.) or in normoxia. After euthanasia, we removed the brain and the heart and isolated brain mitochondria, subsarcolemmal (SSM) and interfibrillar (IFM) heart mitochondria [3]. Mitochondrial bioenergetics was assessed by Clark-type electrode, testing for oxidative phosphorylation (OXPHOS): complex I (glutamate plus malate), complex II (rotenone plus succinate), complex III (rotenone plus durohydroquinone), complex IV (rotenone plus tetramethyl-p-phenylenediamine and ascorbate), Palmitoyl CoA as lipid substrate and adding at the end of the assay dinitrophenol (DNP) to test uncoupled respiration with these substrates.

After acute hypoxia, brain male mitochondria showed an increase of uncoupled respiration at complex II and IV, whereas female mitochondria displayed no significant difference compared to controls.

In heart male IFM mitochondria, following acute hypoxia, ADP/O decreased at complex I and II, compared with controls. Furthermore, in the same complexes data showed an increase of respiratory control ratio, but only complex I resulted statistically significant. These data suggest that hypoxia induced a mild uncoupling of IFM.

Among female heart mitochondria, SSM only showed a decrease in state 3 of complex II after acute hypoxia.

In conclusion, in both genders cardiac and brain mitochondrial bioenergetics change after athletic training in acute hypoxia.

It seems that in female cardiac mitochondria hypoxia induced an impairment of complex II activity, while in male heart mitochondria the result need further investigation as it could be linked to a reported increased activity of ATPase under hypoxia [4] or a defective OXPHOS with a possible enhanced ROS production.

In male brain mitochondria the increased of uncoupled respiration might be linked to a better efficiency of electron transfer system (ETS). Future studies will need to verify these results.

  1. Horscroft JA, Kotwica AO, Laner V, West JA, Hennis PJ, Levett DZH, Howard DJ, Fernandez BO, Burgess SL, Ament Z, Gilbert-Kawai ET, Vercueil A, Landis BD, Mitchell K, Mythen MG, Branco C, Johnson RS, Feelisch M, Montgomery HE, Griffin JL, Grocott MPW, Gnaiger E, Martin DS, Murray AJ (2017) Metabolic basis to Sherpa altitude adaptation. https://doi.org/10.1073/pnas.1700527114
  2. Levett DZ, Radford EJ, Menassa DA, Graber EF, Morash AJ, Hoppeler H, Clarke K, Martin DS, Ferguson-Smith AC, Montgomery HE, Grocott MP, Murray AJ; Caudwell Xtreme Everest Research Group (2012) Acclimatization of skeletal muscle mitochondria to high-altitude hypoxia during an ascent of Everest. https://doi.org/10.1096/fj.11-197772
  3. Palmer JW, Tandler B, Hoppel CL (1977) Biochemical properties of subsarcolemmal and interfibrillar mitochondria isolated from rat cardiac muscle. https://www.jbc.org/article/S0021-9258(19)75283-1/pdf
  4. Kioka H, Kato H, Fujikawa M, Tsukamoto O, Suzuki T, Imamura H, Nakano A, Higo S, Yamazaki S, Matsuzaki T, Takafuji K, Asanuma H, Asakura M, Minamino T, Shintani Y, Yoshida M, Noji H, Kitakaze M, Komuro I, Asano Y, Takashima S (2014) Evaluation of intramitochondrial ATP levels identifies G0/G1 switch gene 2 as a positive regulator of oxidative phosphorylation. https://doi.org/10.1073/pnas.1318547111

โ€ข Keywords: Hypoxia, Heart mitochondria, Brain mitochondria, Clark-type electrode, Trained rats โ€ข Bioblast editor: Plangger M


Affiliations and support

Isola R1, Noli R1, Isola M1, Crisafulli A2, Vargiu R1, Loy F1, Lai Y1
  1. Dept Biomedical Sciences, Univ. of Cagliari, Italy
  2. Department of Medical Sciences and Public Health, University of Cagliari, Italy. - isola@unica.it
This work was supported by the Sardinian Region Government (RAS), Grant RASSR85013 and by Fondazione di Sardegna 2018 call.

List of abbreviations, terms and definitions - MitoPedia

ยป MitoPedia: Terms and abbreviations


Labels: MiParea: Respiration, Comparative MiP;environmental MiP 

Stress:Hypoxia  Organism: Rat  Tissue;cell: Heart, Nervous system  Preparation: Isolated mitochondria 


Coupling state: OXPHOS, ET  Pathway: F, N, S, DQ, CIV  HRR: Oxygraph-2k  Event: Poster