Skip to main content

Advertisement

SpringerLink
Log in

NAD+ Availability and Proteotoxicity

  • Review Paper
  • Published:
NeuroMolecular Medicine Aims and scope Submit manuscript

Abstract

It has been shown that NAD+ availability is important for neuronal survival following ischemia (Liu et al., Neuromolecular Med 11:28–42, 2009). It is proposed here that NAD+ may also control proteotoxicity by influencing both formation and catabolism of altered proteins. It is suggested that low NAD+ availability promotes synthesis of methylglyoxal (MG) which can induce formation of glycated proteins, ROS, and dysfunctional mitochondria. That glyoxalase overexpression and carnosine are both protective against MG and ischemic injury support this proposal. Recognition and elimination of altered proteins is enhanced by NAD+ through effects on stress protein expression and autophagy.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

References

  • Ahmed, N., Battah, S., Karachalias, N., Babeai-Jadidi, R., Horanyi, M., Baroti, K., et al. (2003). Increased formation of methylglyoxal and protein glycation, oxidation and nitration in triosephosphate isomerase deficiency. Biochimica et Biophysica Acta, 1639, 121–132.

    PubMed  CAS  Google Scholar 

  • Aldini, G., Maffei-Fracini, R., Beretta, G., & Carini, M. (2005). Carnosine and related dipeptides as quenchers of reactive carbonyl species: From structural studies to therapeutic perspectives. Biofactors, 24, 77–87. doi:10.1002/biof.5520240109.

    Article  PubMed  CAS  Google Scholar 

  • Alhamdani, M. S., AlKassir, A. H., Abbas, F. K., Jaleel, N. A., & Al-Tace, M. F. (2007). Antiglycation and antioxidant effect of carnosine against glucose degradation products in peritoneal mesothelial cells. Nephron. Clinical Practice, 107, c26–c34. doi:10.1159/000106509.

    Article  PubMed  CAS  Google Scholar 

  • Anderson, R. M., Barger, J. L., Edwards, M. G., Braun, K. H., O’Connor, C. E., Prolla, T. A., et al. (2008). Dynamic regulation of PGC-1α localization and turnover implicates mitochondrial adaptation in caloric restriction and the stress response. Aging Cell, 7, 101–111.

    Article  PubMed  CAS  Google Scholar 

  • Baykara, B., Tekman, I., Pekcetin, C., Ulukus, C., Tuncel, P., Sagol, O., et al. (2009). The protective effects of carnosine and melatonin in ischemia-reperfusion injury in the rat liver. Acta Histochemica, 111, 42–51. doi:10.1016/j.acthis.2008.03.002.

    Article  PubMed  CAS  Google Scholar 

  • Brownson, C., & Hipkiss, A. R. (2000). Carnosine reacts with a glycated protein. Free Radical Biology & Medicine, 28, 1564–1570. doi:10.1016/S0891-5849(00)00270-7.

    Article  CAS  Google Scholar 

  • Cai, W., He, J. C., Zhu, L., Chen, X., Zheng, F., Striker, G. E., et al. (2008). Oral glycotoxins determine the effects of calorie restriction on oxidant stress, age-related diseases and lifespan. American Journal of Pathology, 173, 327–336. doi:10.2353/ajpath.2008.080152.

    Article  PubMed  CAS  Google Scholar 

  • Carini, M., Aldini, G., Beretta, G., Arlandini, E., & Facino, R. M. (2003). Acrolein-sequestering ability of endogenous dipeptides: Characterization of carnosine and homocarnosine/acrolein adducts by electrospray ionization tandem mass spectrometry. Journal of Mass Spectrometry, 38, 996–1006. doi:10.1002/jms.517.

    Article  PubMed  CAS  Google Scholar 

  • Celotto, A. M., Frank, A. C., Seigle, J. L., & Palladino, M. J. (2006). Drosophila model of human inherited triosephosphate isomerase deficiency glycolytic enzymopathy. Genetics, 174, 1237–1246. doi:10.1534/genetics.106.063206.

    Article  PubMed  CAS  Google Scholar 

  • Cunningham, J. T., Rodgers, J. T., Arlow, D. W., Vazquez, F., Mootha, V. K., & Puigserver, P. (2007). mTOR controls mitochondrial oxidative function through a YY1-PGC-1α transcription complex. Nature, 450, 736–740. doi:10.1038/nature06322.

    Article  PubMed  CAS  Google Scholar 

  • Desai, K. M., & Wu, L. (2008). Free radical generation by methylglyoxal in tissues. Drug Metabolism and Drug Interactions, 23, 151–173.

    PubMed  CAS  Google Scholar 

  • Dobrota, D., Fedorova, T., Stvolinsky, S., Babusikova, E., Likacanova, K., Drgova, A., et al. (2005). Carnosine protects the brain of rats and Mongolian gerbils against ischemic injury after stroke. Neurochemical Research, 30, 1283–1288. doi:10.1007/s11064-005-8799-7.

    Article  PubMed  CAS  Google Scholar 

  • Fouad, A. A., El-Rehany, M. A., & Maghraby, H. K. (2007). The hepatoprotective effect of carnosine against ischemia/reperfusion liver injury in rats. European Journal of Pharmacology, 572, 61–68. doi:10.1016/j.ejphar.2007.06.010.

    Article  PubMed  CAS  Google Scholar 

  • Fujii, T., Takaoka, M., Tsuruoka, N., Kiso, Y., Tanaka, T., & Matsumura, Y. (2005). Dietary supplementation of L-carnosine prevents ischemia/reperfusion-induced renal injury in rats. Biological and Pharmaceutical Bulletin, 28, 361–363. doi:10.1248/bpb.28.361.

    Article  PubMed  CAS  Google Scholar 

  • Gnerer, J. P., Kreber, R. A., & Ganetzky, B. (2006). Wasted away, a drososphila mutation in triosephosphate isomerase, causes paralysis, neurodegeneration and early death. Proceedings of the National Academy of Sciences of the United States of America, 103, 14987–14993. doi:10.1073/pnas.0606887103.

    Article  PubMed  CAS  Google Scholar 

  • Guix, F. X., Ill-Raga, G., Bravo, R., Nakaya, T., de Fabritis, G., Coma M, et al. (2009). Amyloid-dependent triosephosphate isomerase nitrotyrosination induces glycation and tau fibrillation. Brain, 132, 1335–1345.

    Google Scholar 

  • Hipkiss, A. R. (2003). Do developmentally-related changes in constitutive proteolysis affect aberrant protein accumulation and generation of the aged phenotype? Mechanisms of Ageing and Development, 124, 575–579. doi:10.1016/S0047-6374(03)00005-8.

    Article  PubMed  CAS  Google Scholar 

  • Hipkiss, A. R. (2006). On the mechanisms of ageing suppression by dietary restriction—is persistent glycolysis the problem? Mechanisms of Ageing and Development, 127, 8–15. doi:10.1016/j.mad.2005.09.006.

    Article  PubMed  CAS  Google Scholar 

  • Hipkiss, A. R. (2008). Energy metabolism, altered proteins, sirtuins and ageing: converging mechanisms? Biogerontol, 9, 49–55. doi:10.1007/s10522-007-9110-x.

    Article  CAS  Google Scholar 

  • Hipkiss, A. R. (2009a). On the enigma of carnosine’s anti-ageing actions. Experimental Gerontology, 44, 237–242. doi:10.1016/j.exger.2008.11.001.

    Article  PubMed  CAS  Google Scholar 

  • Hipkiss, A. R. (2009b). Error-protein metabolism and ageing. Biogerontology. doi:10.1007/s10522-008-9188-9.

  • Hipkiss, A. R., & Chana, H. (1998). Carnosine protects proteins against methylglyoxal-mediated modifications. Biochemical and Biophysical Research Communications, 248, 28–32. doi:10.1006/bbrc.1998.8806.

    Article  PubMed  CAS  Google Scholar 

  • Hipkiss, A. R., Michaelis, J., & Syrris, P. (1995). Non-enzymic glycosylation of the dipeptide L-carnosine, a potential anti-protein-cross-linking agent. FEBS Letters, 371, 81–85. doi:10.1016/0014-5793(95)00849-5.

    Article  PubMed  CAS  Google Scholar 

  • Kumagai, T., Nangaku, M., Kojima, I., Nagai, R., Ingelfinger, J. R., Miyata, T., et al. (2009). Glyoxalase-1 overexpression ameliorates renal ischemia-reperfusion injury in rats. American Journal of Physiology. Renal Physiology, 296, F912–F921. doi:10.1152/ajprenal.90575.2008.

    Article  PubMed  CAS  Google Scholar 

  • Kurata, H., Fujii, T., Tsutsui, H., Katayama, T., Ohkita, M., Takaoka, M., et al. (2006). Renoprotective effects of L-carnosine on ischemia/reperfusion-induced injury in rats. Journal of Pharmacology and Experimental Therapeutics, 319, 640–647. doi:10.1124/jpet.106.110122.

    Article  PubMed  CAS  Google Scholar 

  • Lee, I. H., Cao, L., Mostoslavsky, R., Lombard, D. B., Liu, J., Bruns, N., et al. (2008). A role for the NAD-dependent deacetylase Sirt1 in the regulation of autophagy. Proceedings of the National Academy of Sciences of the United States of America, 105, 3374–3379. doi:10.1073/pnas.0712145105.

    Article  PubMed  CAS  Google Scholar 

  • Liu, D. L., Gharavi, R., Pitta, M., Gleichmann, M., & Mattson, M. P. (2009). Nicotinamide prevents NAD+ depletion and protects neurones against excitotoxicity and cerebral ischemia: NAD+ consumption by SIRT1 may endanger energetically compromised neurons. Neuromolecular Medicine, 11, 28–42. doi:10.1007/s12017-009-8058-1.

    Article  PubMed  CAS  Google Scholar 

  • McFarland, G. A., & Holliday, R. (1994). Retardation of senescence in cultured human diploid fibroblasts by carnosine. Experimental Cell Research, 212, 167–175. doi:10.1006/excr.1994.1132.

    Article  PubMed  CAS  Google Scholar 

  • Min, J., Senut, M. C., Rajanikant, K., Greenberg, E., Bandagi, R., Zemke, D., et al. (2008). Differential neuroprotective effects of carnosine, anserine and N-acetylcarnosine against permanent focal ischemia. Journal of Neuroscience Research, 86, 2984–2991. doi:10.1002/jnr.21744.

    Article  PubMed  CAS  Google Scholar 

  • Morcos, M., Du, X., Pfisterer, F., Hutter, H., Sayed, A. A., Baynes, J., et al. (2008). Glyoxalase-1 prevents mitochondrial protein modification and enhances lifespan in Caenorhabditis elegans. Aging Cell, 7, 260–269. doi:10.1111/j.1474-9726.2008.00371.x.

    Article  PubMed  CAS  Google Scholar 

  • Nicolay, J. P., Schneider, J., Niemoeller, O. M., Artune, F., Portero-Otin, M., Hair, G., Jr., et al. (2006). Stimulation of cell suicide by methylglyoxal. Cellular Physiology and Biochemistry, 18, 223–232. doi:10.1159/000097669.

    Article  PubMed  CAS  Google Scholar 

  • Oya, T., Hatton, N., Mizuno, S., Maeda, S., Osawa, T., & Uchida, K. (1999). Methylglyoxal modification of protein. Chemical and immunochemical characterization of methylglyoxal-arginine adducts. Journal of Biological Chemistry, 274, 18492–18502. doi:10.1074/jbc.274.26.18492.

    Article  PubMed  CAS  Google Scholar 

  • Rabbani, N., & Thornalley, P. J. (2008a). The dicarbonyl proteome: proteins susceptible to dicarbonyl glycation at functional sites in health, aging and disease. Annals of the New York Academy of Sciences, 1126, 124–127. doi:10.1196/annals.1433.043.

    Article  PubMed  CAS  Google Scholar 

  • Rabbani, N., & Thornalley, P. J. (2008b). Dicarbonyls linked to damage to the powerhouse: Glycation of mitochondrial proteins and oxidative stress. Biochemical Society Transactions, 38, 1045–1050. doi:10.1042/BST0361045.

    Article  Google Scholar 

  • Rajanikant, G. K., Zemke, D., Senut, M. C., Frenkel, M. B., Chen, A. F., Gupta, R., et al. (2007). Carnosine is neuroprotective against permanent focal cerebral ischemia in mice. Stroke, 38, 3023–3031. doi:10.1161/STROKEAHA.107.488502.

    Article  PubMed  CAS  Google Scholar 

  • Salminen, A., & Kaamiranta, K. (2009). SIRT1: Regulation of longevity via autophagy. Cell Signalling (in press). doi:10:1016/jcellsig.200902.014.

  • Schneider, A. S. (2000). Triosephosphate isomerase deficiency: Historical perspectives and molecular aspects. Bailliere’s Best Practice & Research. Clinical Haematology, 13, 119–140. doi:10.1053/beha.2000.0061.

    Article  CAS  Google Scholar 

  • Seidler, N. W. (2000). Carnosine prevents glycation-induced changes in electrophoretic mobility of aspartate aminotransferase. Journal of Biochemical and Molecular Toxicology, 14, 215–220. doi:10.1002/(SICI)1099-0461(2000)14:4<215::AID-JBT6>3.0.CO;2-Z.

    Article  PubMed  CAS  Google Scholar 

  • Sejersen, H., & Rattan, S. I. (2009). Dicarbonyl-induced accelerated aging in vitro in human skin fibroblasts. Biogerontology, 10, 203–211. doi:10.1007/s10522-008-9172-4.

    Article  PubMed  CAS  Google Scholar 

  • Shinohara, M., Thornalley, P. J., Giardino, I., Beisswenger, P., Thorpe, S. R., Onorato, J., et al. (1998). Overexpression of glyoxalase-1 in bovine endothelial cells inhibits intracellular advanced glycation endproduct formation and prevents hyperglycemia-induced increases in macromolecular endocytosis. Journal of Clinical Investigation, 101, 1142–1147. doi:10.1172/JCI119885.

    Article  PubMed  CAS  Google Scholar 

  • Tang, S. C., Arumugam, T. V., Cutler, R. G., Jo, D. G., Magnus, T., Chan, S. L., et al. (2007). Neurpoprotective actions of a histidine analogue in models of ischemic stroke. Journal of Neurochemistry, 101, 729–736. doi:10.1111/j.1471-4159.2006.04412.x.

    Article  PubMed  CAS  Google Scholar 

  • Thornalley, P. J. (2008). Protein and nucleotide damage by glyoxal and methylglyoxal in physiological systems–role in aging and disease. Drug Metabolism and Drug Interactions, 23, 125–150.

    PubMed  CAS  Google Scholar 

  • Westerheide, S. D., Anckar, J., Stevens, S. M., Jr., Sistomen, L., & Morimoto, R. I. (2009). Stress-induced regulation of the heat shock factor 1 by the deacetylase SIRT1. Science, 323, 1063–1066. doi:10.1126/science.1165946.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. School of Clinical and Experimental Medicine, College of Medical and Dental Sciences, The University of Birmingham, Edgbaston, Birmingham, B15 2TT, UK

    Alan R. Hipkiss

Authors
  1. Alan R. Hipkiss
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Alan R. Hipkiss.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Hipkiss, A.R. NAD+ Availability and Proteotoxicity. Neuromol Med 11, 97–100 (2009). https://doi.org/10.1007/s12017-009-8069-y

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12017-009-8069-y

Keywords

Search

Navigation