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Antioxidant activity in Spalax ehrenbergi: a possible adaptation to underground stress

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Abstract

The blind subterranean mole rat Spalax ehrenbergi superspecies has evolved adaptive strategies to cope with underground stress. Hypoxia is known to stimulate reactive oxygen species generation; however, mechanisms by which Spalax counteracts oxidative damage have not been investigated before. We studied in Spalax the oxidative status of the Harderian gland (HG), an organ which is particularly vulnerable to oxidative stress in many rodents. With regard to the sexual dimorphism found in this gland, differences between males and females were determined and compared to the surface-dwelling Syrian hamster. Our results show, for the first time, that Spalax exhibits remarkably low biomolecular damage, which implies the existence of physiological strategies to avoid oxidative damage under fluctuating O2 and CO2 levels existing in the mole rat’s subterranean niche. Correspondingly, main antioxidant enzymes, such as superoxide dismutase (SOD), catalase, and glutathione reductase (GR), exhibited high activities in both genders; in particular, remarkably high levels were measured in SOD. SOD and GR activities showed statistically significant differences between sexes. Melatonin, an important circadian agent is also a very important antioxidant molecule and is synthesized in the Harderian glands (HGs) of Spalax. Therefore, the possible interaction between antioxidant enzymes and melatonin is suggested.

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Abbreviations

CAT:

Catalase

GR:

Glutathione reductase

HG:

Harderian gland

HIF-1:

Hypoxia-inducible factor-1

LPO:

Lipid peroxidation

PD:

Protein damage

ROS:

Reactive oxygen species

SOD:

Superoxide dismutase

References

  • Antolín I, Rodríguez C, Sáinz RM, Mayo JC, Uría H, Kotler ML, Rodríguez-Colunga MJ, Tolivia D, Menéndez-Peláez A (1996) Neurohormone melatonin prevents cell damage: effect on gene expression for antioxidant enzymes. FASEB J 10:882–890

    PubMed  Google Scholar 

  • Arieli R, Heth G, Nevo E, Hoch D (1986) Hematocrit and hemoglobin concentration in four chromosomal species and some isolated populations of actively speciating subterranean mole rats in Israel. Experientia 42:441–443

    Article  PubMed  CAS  Google Scholar 

  • Arieli R, Nevo E (1991) Hypoxic survival differs between two mole rat species of humid and arid habitats. Comp Biochem Physiol 100:543–545

    Article  CAS  Google Scholar 

  • Ashur-Fabian O, Avivi A, Trakhtenbrot L, Adamsky K, Cohen M, Kajakaro G, Joel A, Amariglio N, Nevo E, Rechavi G (2004) Evolution of p53 in hypoxia-stressed Spalax mimics human tumor mutation. Proc Natl Acad Sci USA 101:12236–12241

    Article  PubMed  CAS  Google Scholar 

  • Avivi A, Resnick MB, Nevo E, Joel A, Levy AP (1999) Adaptive hypoxic tolerance in the subterranean mole rat Spalax ehrenbergi: the role of vascular endothelial growth factor. FEBS Lett 452:133–140

    Article  PubMed  CAS  Google Scholar 

  • Avivi A, Albrecht U, Oster H, Joel A, Beiles A, Nevo E (2001) Biological clock in total darkness: The Clock/MOP3 circadian system of the blind subterranean mole rat. Proc Natl Acad Sci USA 98:13751–13756

    Article  PubMed  CAS  Google Scholar 

  • Avivi A, Oster H, Joel A, Beiles A, Albrecht U, Nevo E (2002) Circadian genes in a blind subterranean mammal II: Conservation and uniqueness of the three Period homologs in the blind subterranean mole rat, Spalax ehrenbergi superspecies. Proc Natl Acad Sci USA 99:11718–11723

    Article  PubMed  CAS  Google Scholar 

  • Avivi A, Oster H, Joel A, Beiles A, Albrecht U, Nevo E (2004) Circadian genes in a blind subterranean mammal III: molecular cloning and circadian regulation of cryptochrome genes in the blind subterranean mole rat, Spalax ehrenbergi superspecies. J Biol Rhythms 19:22–34

    Article  PubMed  CAS  Google Scholar 

  • Avivi A, Shams I, Joel A, Lache O, Levy AP, Nevo E (2005) Increased blood vessel density provides the mole rat physiological tolerance to its hypoxic subterranean habitat. FASEB J 19:1314–1316

    PubMed  CAS  Google Scholar 

  • Balemans MGM, Pevet P, Legerstee WC, Nevo E (1980) Preliminary investigations on melatonin and 5-methoxytryptophol synthesis in the pineal, retina and Harderian gland of the mole rat and in the pineal of the mouse “eyeless”. J Neural Trans 49:247–255

    Article  CAS  Google Scholar 

  • Burlington RF, Maher JT (1968) Effect of anoxia on mechanical performance of isolated atria from ground squirrels and rats acclimatized to altitude. Nature 219:1370–1371

    Article  PubMed  CAS  Google Scholar 

  • Carriere A, Carmona MC, Fernandez Y, Rigoulet M., Wenger RH, Penicaud L, Casteilla L (2004) Mitochondrial reactive oxygen species control the transcription factor CHOP-10/GADD153 and adipocyte differentiation: a mechanism for hypoxia-dependent effect. J Biol Chem 279:40462–40469

    Article  PubMed  CAS  Google Scholar 

  • Cassone VM (1990) Effects of melatonin on vertebrate circadian systems. Trends Neurosci 13:457–464

    Article  PubMed  CAS  Google Scholar 

  • Chandel NS, Maltepe E, Goldwasser E, Mathieu CE, Simon MC, Schumacker PT (1998) Mitochondrial reactive oxygen species trigger hypoxia-induced transcription. Proc Natl Acad Sci 95:11715–11720

    Article  PubMed  CAS  Google Scholar 

  • Chandel NS, McClintock DS, Feliciano CE, Wood TM, Melendez JA, Rodriguez AM, Schumacker PT (2000) Reactive oxygen species generated at mitochondrial complex III stabilize hypoxia-inducible factor-1alpha during hypoxia: a mechanism of O2 sensing. J Biol Chem 275:25130–25138

    Article  PubMed  CAS  Google Scholar 

  • Chen Q, Vazquez E J, Moghaddas S, Hoppel CL, Lesnefsky EJ (2003) Production of reactive oxygen species by mitochondria: central role of complex III. J Biol Chem 278:36027–36031

    Article  PubMed  CAS  Google Scholar 

  • Coto-Montes A, Hardeland R (1999) Antioxidative effects of melatonin in Drosophila melanogaster: antagonization of damage induced by the inhibition of catalase. J Pineal Res 27:154–158

    Article  PubMed  CAS  Google Scholar 

  • Coto-Montes A, Boga JA, Tomás-Zapico C, Rodríguez –Colunga MJ, Martínez-Fraga J, Tolivia-Cadrecha D, Menéndez G, Hardeland R, Tolivia D (2001a) Physiological oxidative stress model: Syrian hamster Harderian gland—sex differences in antioxidant enzymes. Free Radic Biol Med 30:785–792

    Article  CAS  Google Scholar 

  • Coto-Montes A, Boga JA, Tomás-Zapico C, Rodríguez-Colunga MJ, Martínez-Fraga J, Tolivia-Cadrecha D, Menéndez G, Hardeland R, Tolivia D (2001b) Porphyric enzymes in hamster Harderian gland, a model of damage by porphyrins and their precursors. A chronobiological study on the role of sex differences. Chem Biol Interact 134:135–149

    Article  CAS  Google Scholar 

  • Epstein AC, Gleadle JM, McNeill LA, Hewitson KS, O’Rourke J, Mole DR, Mukherji M, Metzen E, Wilson MI, Dañad A, Tian YM, Masson N, Hamilton DL, Jaakkola P, Barstead R, Hodgkin J, Maxwell PH, Pugh CW, Schofield CJ, Ratcliffe PJ (2001) C. elegans EGL-9 and mammalian homologs define a family of dioxygenases that regulate HIF by prolyl hydroxylation. Cell 107:43–54

    Article  PubMed  CAS  Google Scholar 

  • Freeman RS, Hasbani DM, Lipscomb EA, Straub JA, Xie L (2003) SM-20, EGL-9, and the EGLN family of hypoxia-inducible factor prolyl hydroxylases. Mol Cells 16:1–12

    PubMed  CAS  Google Scholar 

  • Gilad E, Shanas U, Terkel J, Zisapel N (1997) Putative melatonin receptors in the blind mole rat Harderian gland. J Exp Zool 277:435–441

    Article  PubMed  CAS  Google Scholar 

  • Goldman BD, Goldman SL, Riccio AP, Terkel J (1997) Circadian patterns of locomotor activity and body temperature in blind mole rats, Spalax ehrenbergi. J Biol Rhythms 12:348–361

    Article  PubMed  CAS  Google Scholar 

  • Gurnett AM, McConnell JP, Harris DE, Lehmann H, Joysey KA, Nevo E (1984) The myoglobin of rodents-Lagostomus-maximus (viscacha) and Spalax ehrenbergi (mole rat). J Prot Chem 3:445–454

    Article  CAS  Google Scholar 

  • Hardeland R, Balzer I, Poeggeler B, Fuhrberg B, Uría H, Behrmann G, Wolf R, Meyer TJ, Reiter RJ (1995) On the primary functions of melatonin in evolution: mediation of photoperiodic signals in a unicell, photooxidation, and scavenging of free radicals. J Pineal Res 18:104–111

    Article  PubMed  CAS  Google Scholar 

  • Hardeland R, Coto-Montes A, Poeggeler B (2003) Circadian rhythms, oxidative stress and antioxidative defense mechanisms. Chronobiol Int 20:921–962

    Article  PubMed  CAS  Google Scholar 

  • Hopfl G, Ogunshola O, Gassmann M (2004) HIFs and tumors-causes and consequences. Am J Physiol Regul Integr Comp Physiol 286:608–623

    Google Scholar 

  • Kerem D, Hammond DD, Elsner R (1973) Tissue glycogen levels in the Weddell seal, Leptonychotes weddelli: a possible adaptation to asphyxial hypoxia. Comp Biochem Physiol A 45:731–736

    Article  PubMed  CAS  Google Scholar 

  • Kleinschmidt T, Nevo E, Braunitzer G (1984) The primary structure of the hemoglobin of the mole rat (Spalax ehrenbergi, rodentia, chromosome species 60). Hoppe Seylers Z Physiol Chem 365:531–537

    PubMed  CAS  Google Scholar 

  • Kum-Tatt L, Tan IK, Seet AM (1975) A new colorimetric method for the determination of NADH/NADPH dependent glutathione reductase in erythrocytes and in plasma. Clin Chem Acta 58:101–108

    Article  CAS  Google Scholar 

  • Lando D, Peet DJ, Gorman JJ, Whelan DA, Whitelaw ML, Bruick RK (2002) FIH-1 is an asparaginyl hydroxylase enzyme that regulates the transcriptional activity of hypoxia-inducible factor. Genes Dev 16:1466–1471

    Article  PubMed  CAS  Google Scholar 

  • Levine RL, Garland D, Oliver CN, Amici A, Climent I, Lenz AG, Ahn BW, Shaltiel S, Stadtman ER (1990) Determination of carbonyl content in oxidatively modified proteins. Methods Enzymol 186:464–78

    Article  PubMed  CAS  Google Scholar 

  • Lubinsky S, Bewley GC (1979) Genetics of catalase in Drosophila melanogaster: Rates of synthesis and degradation of the enzyme in flies aneuploid and euploid for the structural gene. Genetics 9:723–742

    Google Scholar 

  • Mansfield KD, Simon MC, Keith B (2004) Hypoxic reduction in cellular glutathione levels requires mitochondrial reactive oxygen species. J Appl Physiol 97:1358–1366

    Article  PubMed  CAS  Google Scholar 

  • Martin JPJR, Daily M, Sugarman E (1987) Negative and positive assays of superoxide dismutase based on hematoxylin autoxidation. Arch Biochem Biophys 255:329–336

    Article  PubMed  CAS  Google Scholar 

  • Menéndez-Peláez A, López-González MA, Guerrero JM (1993) Melatonin binding sites in the Harderian gland of Syrian hamsters: sexual differences and effect of castration. J Pineal Res 14:34–38

    Article  PubMed  Google Scholar 

  • Nevo E (1991) Evolutionary theory and processes of active speciation and adaptative radiation in subterranean mole rats, Spalax ehrenbergi superspecies, in Israel. Evol Bio 25:1–125

    Google Scholar 

  • Nevo E (1998) Evolution of a visual system if life without light: optimization via tinkering in blind mole rats. In: Weibel ER, Taylor CR, Bolis C (eds) Principles of animal design. Cambridge University Press, Cambridge, pp 288–298

    Google Scholar 

  • Nevo E (1999) Mosaic evolution of subterranean mammals: regression, progression, and global convergence. Oxford University Press, New York

    Google Scholar 

  • Nevo E, Ben-Shlomo R, Maeda N (1989) Haptoglobin DNA polymorphism in subterranean mole rats of the Spalax ehrenbergi superspecies in Israel. Heredity 62:85–90

    Article  PubMed  Google Scholar 

  • Nevo E, Ivanitskaya E, Beiles A (2001) Adaptive Radiation of Blind Subterranean Mole Rats. Backhuys, Leiden

    Google Scholar 

  • Payne AP (1994) The Harderian gland: a tercentennial review. J Anat 185:1–49

    PubMed  Google Scholar 

  • Pevet P, Heth G, Hiam A, Nevo E (1984) Photoperiod perception in the blind mole rat (Spalax ehrenbergi, Nehring): involvement of the Harderian gland, atrophied eyes, and melatonin. J Exp Zool 232:41–50

    Article  PubMed  CAS  Google Scholar 

  • Poeggeler B, Saarela S, Reiter RJ, Tan DX, Chen LD, Manchester LC, Barlow-Walden LR (1994) Melatonin–a highly potent endogenous radical scavenger and electron donor: new aspects of the oxidation chemistry of this indole accessed in vitro. Ann N Y Acad Sci 738:419–420

    Article  PubMed  CAS  Google Scholar 

  • Princ FG, Maxit AG, Cardalda C, Batlle A, Juknat AA (1998) In vivo protection by melatonin against delta-aminolevulinic acid-induced oxidative damage and its antioxidant effect on the activity of haem enzymes. J Pineal Res 24:1–8

    Article  PubMed  CAS  Google Scholar 

  • Sanyal S, Jansen HG, de Grip WJ, Nevo E, de Jong WW (1990) The eye of the blind mole rat, Spalax ehrenbergi. Rudiment with hidden function? Invest Ophthalmol Vis Sci 31:1398–1404

    PubMed  CAS  Google Scholar 

  • Schroedl C, McClintock DS, Budinger GR, Chandel NS (2002) Hypoxic but not anoxic stabilization of HIF-1alpha requires mitochondrial reactive oxygen species. Am J Physiol Lung Cell Mol Physiol 283:922–931

    Google Scholar 

  • Shams I, Avivi A, Nevo E (2004) Hypoxic stress tolerance of the blind subterranean mole rat: expression of erythropoietin and hypoxia-inducible factor 1 alpha. Proc Natl Acad Sci USA 101:9698–9703

    Article  PubMed  CAS  Google Scholar 

  • Shams I, Avivi A. Nevo E (2005a) Adaptation of blind mole rats to life underground: O2 and CO2 fluctuations in burrows. Comp Biochem Physiol Part A (in press)

  • Shams I, Nevo E, Avivi A (2005b) Ontogenetic expression of erythropoietin and hypoxia-inducible factor-1 alpha genes in subterranean blind mole rats. FASEB J 19:307–309

    CAS  Google Scholar 

  • Shanas U, Arensburg B, Hammel I, Hod I, Terkel J (1996) Quantitative histomorphology of the blind mole rat Harderian gland. J Anat 188:341–347

    PubMed  Google Scholar 

  • Stroev SA, Gluschenko TS, Tjulkova EI, Rybnikova EA, Samoilov MO, Pelto-Huikko M (2005) The effect of preconditioning on the Cu, Zn superoxide dismutase expression and enzyme activity in rat brain at the early period after severe hypobaric hypoxia. Neurosci Res (in press)

  • Tomás-Zapico C, Martínez-Fraga J, Rodríguez-Colunga MJ, Tolivia D, Hardeland R, Coto-Montes A (2002a) Melatonin protects against delta-aminolevulinic acid-induced oxidative damage in male Syrian hamster Harderian glands. Int J Biochem Cell Biol 34:544–553

    Article  Google Scholar 

  • Tomás-Zapico C, Coto-Montes A, Martínez-Fraga J, Rodríguez-Colunga MJ, Hardeland R, Tolivia D (2002b) Effects of delta-aminolevulinic acid and melatonin in the Harderian gland of female Syrian hamsters. Free Radic Biol Med 32:1197–1204

    Article  Google Scholar 

  • Tomás-Zapico C, Coto-Montes A, Martínez-Fraga J, Rodríguez-Colunga MJ, Tolivia D (2003) Effects of continuous light exposure on antioxidant enzymes, porphyric enzymes and cellular damage in the Harderian gland of the Syrian hamster. J Pineal Res 34:60–68

    Article  PubMed  Google Scholar 

  • Wang GL, Semenza GL (1995) Purification and characterization of hypoxia-inducible factor 1. J Biol Chem 270:1230–1237

    Article  PubMed  CAS  Google Scholar 

  • Wellman TL, Jenkins J, Penar PL, Tranmer B, Zahr R, Lounsbury KM (2004) Nitric oxide and reactive oxygen species exert opposing effects on the stability of hypoxia-inducible factor-1alpha (HIF-1alpha) in explants of human pial arteries. FASEB J 18:379–381

    PubMed  CAS  Google Scholar 

  • Widmer H P, Hoppeler H, Nevo E, Taylor C R, Weibel E W (1997) Working underground: respiratory adaptations in the blind mole rat. Proc Natl Acad Sci USA 94:2062–267

    Article  PubMed  CAS  Google Scholar 

  • Zou A-P, Cowley AW Jr (2003) Reactive oxygen species and molecular regulation of renal oxygenation. Acta Physiol Scand 179:233–241

    Article  PubMed  CAS  Google Scholar 

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Acknowledgment

This work was partially performed with grants FIS GO3/137 from the Instituto de Salud Carlos III (Spain) and CAL03-074-C2 from INIA, Spain. BC is a FYCIT predoctoral fellow from Principado de Asturias, Spain; CT-Z is a F.P.U. predoctoral fellow from the Secretaría de Estado y Universidades, Spain; AC-M is a researcher from the Ramón y Cajal Program, (Ministerio de Ciencia y Tecnología/Universidad de Oviedo), Spain. E.N and A.A thank the Ancell-Teicher Research Foundation for Genetics and Molecular Evolution for financial support.

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Authors and Affiliations

  1. Department of Morphology and Cellular Biology, Faculty of Medicine, University of Oviedo, C/ Julián Clavería s/n, 33006, Oviedo, Spain

    Beatriz Caballero, Cristina Tomás-Zapico, Ignacio Vega-Naredo, Verónica Sierra, Delio Tolivia, María Josefa Rodríguez-Colunga & Ana Coto-Montes

  2. Institut für Zoologie und Anthropologie der Göttingen Universität, 37073, Göttingen, Germany

    Rüdiger Hardeland

  3. Laboratory of Animal Molecular Evolution, Institute of Evolution, University of Haifa, Mount Carmel, 31905, Haifa, Israel

    Alma Joel, Eviatar Nevo & Aaron Avivi

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  1. Beatriz Caballero
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  2. Cristina Tomás-Zapico
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  3. Ignacio Vega-Naredo
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  4. Verónica Sierra
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  5. Delio Tolivia
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  6. Rüdiger Hardeland
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  7. María Josefa Rodríguez-Colunga
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  8. Alma Joel
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  9. Eviatar Nevo
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  10. Aaron Avivi
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  11. Ana Coto-Montes
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Correspondence to Ana Coto-Montes.

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Joint senior authorship: Aaron Avivi and Ana Coto-Montes

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Caballero, B., Tomás-Zapico, C., Vega-Naredo, I. et al. Antioxidant activity in Spalax ehrenbergi: a possible adaptation to underground stress. J Comp Physiol A 192, 753–759 (2006). https://doi.org/10.1007/s00359-006-0111-z

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  • DOI: https://doi.org/10.1007/s00359-006-0111-z

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