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Effect of graded corticosterone treatment on aging-related markers of oxidative stress in rat liver mitochondria

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Abstract

Caloric restriction (CR) decreases aging rate and lowers the rate of reactive oxygen species (ROS) production at mitochondria in different organs, but the signal responsible for this last change is unknown. Glucocorticoids could constitute such a signal since it is well known that their levels increase during CR, and available studies failed to find consistent effects of insulin, the other better described hormone that varies during CR, on mitochondrial oxidative stress. In addition, there is almost no information on the possible in vivo effects of glucocorticoids on specific markers of mitochondrial and tissue oxidative stress. In this investigation, male Wistar rats were treated with corticosterone at doses of 150 and 400 mg/kg of diet during 4 weeks. After that time, oxidative stress-related parameters were measured in the liver. The corticosterone treatments did not change the rate of ROS production or the rate of oxygen consumption of rat liver mitochondria. The two lipoxidation protein markers measured (malondialdehyde-lysine and carboxymethyllysine) were decreased by both corticosterone treatments. These changes were associated with decreases in fatty acid unsaturation, especially with lowered levels of the highly unsaturated araquidonic and docosahexaenoic acids, which decrease the sensitivity to lipid peroxidation processes. The specific protein carbonyl glutamic semialdehyde, a marker of protein oxidation, was also lowered at 400 mg/kg corticosterone. The protein glycoxydation marker carboxyethyllysine and the level of oxidative damage to mtDNA (8–oxo-7,8-dihydro-2 9-deoxyguanosine) were increased by corticosterone. The results do not support the idea that corticosterone is the signal responsible for the decrease in mitochondrial ROS generation during CR. However, they show that this hormone modulates the level of oxidative stress both in proteins and in mtDNA. Some of these changes can contribute to the chronic effects of the hormone at tissue level.

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Abbreviations

AASA:

aminoadipic semialdehyde in proteins

CEL:

carboxyethyl-lysine in proteins

CML:

carboxymethyl-lysine in proteins

DBI:

double bond index

GSA:

glutamic semialdehyde in proteins

MDAL:

malondialdehyde-lysine in proteins

MitROS:

mitochondrial ROS

MtDNA:

mitochondrial DNA

8-oxodG:

8-oxo-7,8-dihydro-2 9-deoxyguanosine

ROS:

reactive oxygen species

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Acknowledgements

This study was supported in part by I + D grants from the Spanish Ministry of Science and Technology (BFI2003–01287), the Generalitat of Catalunya (Department d 9Universitats, Recerca, i Societat de la Informació, DURSI, ref. 2005SGR00101), and the Spanish Ministry of Health (FIS 02–0891, 04–0355, and 05–2241) to R.P., from Fundacio la Caixa to R.P. and M.P.O, and from the Spanish Ministry of Science and Education (BFU2005–02584) to G.B. P. Caro and A. Sanz received a predoctoral fellowship from the Ministry of Science and Education and from the Complutense University, respectively.

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Authors and Affiliations

  1. Department of Animal Physiology-II, Facultad de Ciencias Biológicas, Complutense University, c/Antonio Novais-2, Madrid , 28040, Spain

    Pilar Caro, José Gómez, Alberto Sanz & Gustavo Barja

  2. Department of Basic Medical Sciences, University of Lleida, Lleida , 25008, Spain

    Manel Portero-Otín & Reinald Pamplona

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  1. Pilar Caro
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  2. José Gómez
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  3. Alberto Sanz
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  4. Manel Portero-Otín
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  5. Reinald Pamplona
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  6. Gustavo Barja
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Correspondence to Gustavo Barja.

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Caro, P., Gómez, J., Sanz, A. et al. Effect of graded corticosterone treatment on aging-related markers of oxidative stress in rat liver mitochondria. Biogerontology 8, 1–11 (2007). https://doi.org/10.1007/s10522-006-9026-x

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  • DOI: https://doi.org/10.1007/s10522-006-9026-x

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