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Heme oxygenase 1 expression in rat liver during ageing and ethanol intoxication

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Abstract

Heme oxygenase 1 (HO-1) expression is recognized as a marker of cellular response to oxidative stress; since ageing is believed to be related to oxidative “wear and tear”, HO-1 may represent a candidate biomarker of ageing. In our study, the hepatic expression of HO-1 mRNA, evaluated by RT-PCR in 2.5–24 month-old rats, was higher at 6 months than at 2.5 months of age, but thereafter increased no further: on the contrary, a declining trend was observed. However, while 2.5 month-old rats responded to acute ethanol intoxication by displaying increased expression of liver HO-1 mRNA, and 6 month-old rats exhibited a mild response, 18 month-old rats did not show any response; this phenomenon suggests that during development and ageing the transcriptional response to oxidative stress decreases. In our view, the finding that HO-1 expression did not increase progressively during ageing may be explained by a decreased transcriptional ability to respond to stress in older animals, rather than by a reduction in oxidative stress.

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Abbreviations

HO:

Heme oxygenase

HSP:

Heat shock protein

MDA:

Malondialdehyde

HNE:

4-Hydroxy-2-nonenal

TBA:

Thiobarbituric acid

TCA:

Trichloroacetic acid

References

  • Albano E (2002) Free radical mechanisms in immune reactions associated with alcoholic liver disease. Free Radic Biol Med 32:110–114

    Article  PubMed  CAS  Google Scholar 

  • Bauer M, Bauer I (2002) Heme oxygenase-1: redox regulation and role in the hepatic response to oxidative stress. Antioxid Redox Signal 4:749–758

    Article  PubMed  CAS  Google Scholar 

  • Blake MJ, Fargnoli J, Gershon D, Holbrook NJ (1991) Concomitant decline in heat-induced hyperthermia and HSP70 mRNA expression in aged rats. Am J Physiol 260:R663–R667

    PubMed  CAS  Google Scholar 

  • Calabrese V, Scapagnini G, Ravagna A, Colombrita C, Spadaro F, Butterfield DA, Giuffrida Stella AM (2004) Increased expression of heat shock proteins in rat brain during aging: relationship with mitochondrial function and glutathione redox state. Mech Ageing Dev 125:325–335

    Article  PubMed  CAS  Google Scholar 

  • Calabrese V, Stella AM, Butterfield DA, Scapagnini G (2004) Redox regulation in neurodegeneration and longevity: role of the heme oxygenase and HSP70 systems in brain stress tolerance. Antioxid Redox Signal 6:895–913

    PubMed  CAS  Google Scholar 

  • Chen J, Rider DA, Ruan R (2006) Identification of valid housekeeping genes and antioxidant enzyme gene expression change in the aging rat liver. J Gerontol A Biol Sci Med Sci 61:20–27

    PubMed  Google Scholar 

  • Chen JJ, Yu BP (1994) Alterations in mitochondrial membrane fluidity by lipid peroxidation products. Free Radic Biol Med 17:411–418

    Article  PubMed  CAS  Google Scholar 

  • Choi AM, Alam J (1996) Heme oxygenase-1: function, regulation, and implication of a novel stress-inducible protein in oxidant-induced lung injury. Am J Respir Cell Mol Biol 15:9–19

    PubMed  CAS  Google Scholar 

  • Esterbauer H, Cheeseman KH (1990) Determination of aldehydic lipid peroxidation products: malonaldehyde and 4-hydroxynonenal. Methods Enzymol 186:407–421

    Article  PubMed  CAS  Google Scholar 

  • Finkel T, Holbrook NJ (2000) Oxidants, oxidative stress and the biology of ageing. Nature 408:239–247

    Article  PubMed  CAS  Google Scholar 

  • Harman D (1992) Free radical theory of aging. Mutat Res 275:257–266

    PubMed  CAS  Google Scholar 

  • Heydari AR, Takahashi R, Gutsmann A, You S, Richardson A (1994) Hsp70 and aging. Experientia 50:1092–1098

    Article  PubMed  CAS  Google Scholar 

  • Hoetzel A, Leitz D, Schmidt R, Tritschler E, Bauer I, Loop T, Humar M, Geiger KK, Pannen BH (2006) Mechanism of hepatic heme oxygenase-1 induction by isoflurane. Anesthesiology 104:101–109

    Article  PubMed  CAS  Google Scholar 

  • Huang TT, Carlson EJ, Gillespie AM, Shi Y, Epstein CJ (2000) Ubiquitous overexpression of CuZn superoxide dismutase does not extend life span in mice. J Gerontol A Biol Sci Med Sci 55:B5–B9

    PubMed  CAS  Google Scholar 

  • Jin X, Wang R, Xiao C, Cheng L, Wang F, Yang L, Feng T, Chen M, Chen S, Fu X, Deng J, Wang R, Tang F, Wei Q, Tanguay RM, Wu T (2004) Serum and lymphocyte levels of heat shock protein 70 in aging: a study in the normal Chinese population. Cell Stress Chaperones 9:69–75

    PubMed  CAS  Google Scholar 

  • Keyse SM, Tyrrell RM (1989) Heme oxygenase is the major 32-kDa stress protein induced in human skin fibroblasts by UVA radiation, hydrogen peroxide, and sodium arsenite. Proc Natl Acad Sci U S A 86:99–103

    Article  PubMed  CAS  Google Scholar 

  • Landis GN, Tower J (2005) Superoxide dismutase evolution and life span regulation. Mech Ageing Dev 126:365–379

    Article  PubMed  CAS  Google Scholar 

  • Lavrovsky Y, Song CS, Chatterjee B, Roy AK (2000) Age-dependent increase of heme oxygenase-1 gene expression in the liver mediated by NFkappaB. Mech Ageing Dev 114:49–60

    Article  PubMed  CAS  Google Scholar 

  • Locke M, Tanguay RM (1996) Diminished heat shock response in the aged myocardium. Cell Stress Chaperones 1:251–260

    Article  PubMed  CAS  Google Scholar 

  • Maines MD (1988) Heme oxygenase: function, multiplicity, regulatory mechanisms, and clinical applications. Faseb J 2:2557–2568

    PubMed  CAS  Google Scholar 

  • Mooradian AD (1990) Biomarkers of aging: do we know what to look for? J Gerontol 45:B183–B186

    PubMed  CAS  Google Scholar 

  • Morse D, Choi AM (2002) Heme oxygenase-1: the “emerging molecule” has arrived. Am J Respir Cell Mol Biol 27:8–16

    PubMed  CAS  Google Scholar 

  • Nakanishi Y, Yasumoto K (1997) Induction after administering paraquat of heme oxygenase-1 and heat shock protein 70 in the liver of senescence-accelerated mice. Biosci Biotechnol Biochem 61:1302–1306

    Article  PubMed  CAS  Google Scholar 

  • Njemini R, Demanet C, Mets T (2004) Inflammatory status as an important determinant of heat shock protein 70 serum concentrations during aging. Biogerontology 5:31–38

    Article  PubMed  CAS  Google Scholar 

  • Okuno F, Arai M, Sujita K, Eto S, Ishii H (1991) Alterations in hepatic delta-aminolevulinic acid synthetase and heme oxygenase activities after chronic ethanol consumption in rats. Alcohol 8:449–451

    Article  PubMed  CAS  Google Scholar 

  • Orr WC, Sohal RS (1994) Extension of life-span by overexpression of superoxide dismutase and catalase in Drosophila melanogaster. Science 263:1128–1130

    Article  PubMed  CAS  Google Scholar 

  • Poon HF, Calabrese V, Scapagnini G, Butterfield DA (2004) Free radicals: key to brain aging and heme oxygenase as a cellular response to oxidative stress. J Gerontol A Biol Sci Med Sci 59:478–493

    PubMed  Google Scholar 

  • Ryter SW, Choi AM (2002) Heme oxygenase-1: molecular mechanisms of gene expression in oxygen-related stress. Antioxid Redox Signal 4:625–632

    Article  PubMed  CAS  Google Scholar 

  • Ryter SW, Tyrrell RM (2000) The heme synthesis and degradation pathways: role in oxidant sensitivity. Heme oxygenase has both pro- and antioxidant properties. Free Radic Biol Med 28:289–309

    Article  PubMed  CAS  Google Scholar 

  • Schriner SE, Linford NJ, Martin GM, Treuting P, Ogburn CE, Emond M, Coskun PE, Ladiges W, Wolf N, Van Remmen H, Wallace DC, Rabinovitch PS (2005) Extension of murine life span by overexpression of catalase targeted to mitochondria. Science 308:1909–1911

    Article  PubMed  CAS  Google Scholar 

  • Shibahara S, Muller R, Taguchi H, Yoshida T (1985) Cloning and expression of cDNA for rat heme oxygenase. Proc Natl Acad Sci U S A 82:7865–7869

    Article  PubMed  CAS  Google Scholar 

  • Sohal RS (2002) Role of oxidative stress and protein oxidation in the aging process. Free Radic Biol Med 33:37–44

    Article  PubMed  CAS  Google Scholar 

  • Sohal RS, Orr WC (1992) Relationship between antioxidants, prooxidants, and the aging process. Ann N Y Acad Sci 663:74–84

    Article  PubMed  CAS  Google Scholar 

  • Soti C, Csermely P (2000) Molecular chaperones and the aging process. Biogerontology 1:225–233

    Article  PubMed  CAS  Google Scholar 

  • Stadtman ER (2001) Protein oxidation in aging and age-related diseases. Ann N Y Acad Sci 928:22–38

    Article  PubMed  CAS  Google Scholar 

  • Terry DF, McCormick M, Andersen S, Pennington J, Schoenhofen E, Palaima E, Bausero M, Ogawa K, Perls TT, Asea A (2004) Cardiovascular disease delay in centenarian offspring: role of heat shock proteins. Ann N Y Acad Sci 1019:502–505

    Article  PubMed  CAS  Google Scholar 

  • van der Loo B, Bachschmid M, Labugger R, Schildknecht S, Kilo J, Hahn R, Palacios-Callender M, Luscher TF (2005) Expression and activity patterns of nitric oxide synthases and antioxidant enzymes reveal a substantial heterogeneity between cardiac and vascular aging in the rat. Biogerontology 6:325–334

    Article  PubMed  CAS  Google Scholar 

  • Vasilaki A, Iwanejko LM, McArdle F, Broome CS, Jackson MJ, McArdle A (2003) Skeletal muscles of aged male mice fail to adapt following contractile activity. Biochem Soc Trans 31:455–456

    Article  PubMed  CAS  Google Scholar 

  • Wei YH, Lu CY, Wei CY, Ma YS, Lee HC (2001) Oxidative stress in human aging and mitochondrial disease-consequences of defective mitochondrial respiration and impaired antioxidant enzyme system. Chin J Physiol 44:1–11

    PubMed  CAS  Google Scholar 

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Acknowledgements

This work has been supported by Grants from the University of Genova, MIUR PRIN #2004063943_001 and #2004068552_002, and FIRB 2001 #RBAU01JBH8_003.

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Authors and Affiliations

  1. Department of Experimental Medicine, Section of General Pathology, University of Genova, Via L.B. Alberti 2, 16132 , Genova, Italy

    Stefania Patriarca, Anna Lisa Furfaro, Luana Cosso, Elena Pesce Maineri, Emanuela Balbis, Cinzia Domenicotti, Mariapaola Nitti, Damiano Cottalasso, Umberto Maria Marinari, Maria Adelaide Pronzato & Nicola Traverso

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  1. Stefania Patriarca
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  2. Anna Lisa Furfaro
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  3. Luana Cosso
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Correspondence to Nicola Traverso.

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Stefania Patriarca and Anna Lisa Furfaro equally contributed to this paper.

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Patriarca, S., Furfaro, A.L., Cosso, L. et al. Heme oxygenase 1 expression in rat liver during ageing and ethanol intoxication. Biogerontology 8, 365–372 (2007). https://doi.org/10.1007/s10522-006-9079-x

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  • DOI: https://doi.org/10.1007/s10522-006-9079-x

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