Action of protoporphyrin-IX (PP-IX) in the lifespan of Drosophila melanogaster deficient in endogenous antioxidants, Sod and Cat


Protoporphyirin-IX (PP-IX) is a precursor of the biosynthesis of the hemo group, most of the cytochromes and the chlorophylls. The PP-IX is used for medical purposes, and recently a report indicated that it exhibits a dual action since it can decrease or increase the genetic damage caused by N-nitroso-N-ethylurea (ENU) in somatic cells of Drosophila. PP-IX is known to be able to act as an anti-or pro-oxidant agent. The aim of the present research was to study the role of PP-IX on the lifespan of Drosophila melanogaster, taking into account the fact that increasing levels of ROS can accelerate the aging process. The Canton-S strain (CS) was used as well as Sod and Cat which are deficient in the endogenous enzymes, superoxide dismutase and catalase, respectively. Groups of females and males were treated separately with 5 mg/ml of PP-IX solution. The comparison of survival curves indicates that this pigment extended the lifespan of CS. In contrast, Sod strain showed that the opposite effect and had no effect in Cat strain. The fact that PP-IX reduces the mean lifespan in Sod deficient strain might suggest a pro-oxidant action of PP-IX, and consequently the cumulating of ROS as a superoxide could have a mutagenic effect as was shown recently. The results presented evidence of the dual effect of PP-IX.

Share and Cite:

Pimentel, E. , Vidal, L. , Cruces, M. and Janczur, M. (2013) Action of protoporphyrin-IX (PP-IX) in the lifespan of Drosophila melanogaster deficient in endogenous antioxidants, Sod and Cat. Open Journal of Animal Sciences, 3, 1-7. doi: 10.4236/ojas.2013.34A2001.

Conflicts of Interest

The authors declare no conflicts of interest.


[1] Harman, D. (1956) Aging: A theory based on free radical and radiation chemistry. The Journals of Gerontology, 11, 298-300.
[2] Frei, B., Stocker, R. and Ames, B. (1992) Small molecule antioxidant defenses in human extracellular fluids. In: Scandalios, J., Ed., Molecular Biology of Free Radical Scavenging Systems. Current Communications in Cell and Molecular Biology. Cold Spring Harbor, New York, 23-45.
[3] Halliwell, B. (2006) Oxidative stress and neurodegeneration: Where are we now? Journal of Neurochemistry, 97, 1634-1658.
[4] Simic, M.G. and Jovanovic, S.V. (1990) Mechanisms of inactivation of oxygen radicals by dietary antioxidants and their models. Antimutagenesis and anticarcinogenesis mechanisms II, Basic Life Sciences, 52, 127-137.
[5] Zimmering, S., Olvera, O, Hernandez, M.E., Cruces, M.P., Arceo, C. and Pimentel, E. (1990) Evidence for a radioprotective effect of chlorophyllin in Drosophila. Mutation Research, 245, 47-49.
[6] Cruces, M.P. and Pimentel, A.E. (2006) Antimutagénesis: La clorofilina una alternativa? In: Pimentel, A.E., Ortiz, A. and Brena, M., Ed., Tópicos de Genética, UAEM-SMG, Mexico, 55-75.
[7] Ferguson, L.R. and Philpott, M. (2008) Nutrition and mutagenesis. Annual Review of Nutrition, 28, 313-329.
[8] Ferruzzi, M.G. and Blakeslee, J. (2007) Digestion, absorption, and cancer preventative activity of dietary chlorophyll derivatives. Nutrition Research, 27, 1-12.
[9] Cruces, M.P., Pimentel, E. and Zimmering, S. (2009) Evidence that low concentrations of chlorophyllin (CH LN) increase the genetic damage induced by gamma rays in somatic cells of Drosophila. Mutation Research, 679, 84-86.
[10] Pimentel, E., Cruces, M.P. and Zimmering, S. (2011) A study of the inhibition/promotion effects of sodium-copper chlorophyllin (SCC)-mediated mutagenesis in somatic cells of Drosophila. Mutation Research, 722, 52-55.
[11] Romert, L., Curvall, M. and Jenssen, D. (1992) Chlorophyllin is both a positive and negative modifier of mutagenicity. Mutagenesis, 7, 349-355.
[12] Panek, H. and O’Brian, M.R. (2002) A whole genome view of prokaryotic haem biosynthesis. Microbiology, 148, 2273-2282.
[13] Williams, M., Krootjes, B.H., Van Steveninck, J. and Van Der Zee, J. (1994) The pro-and antioxidant properties of protoporphyrin IX. Biochimica et Biophysica Acta (BBA) —Lipids and Lipid Metabolism, 1211, 310-316.
[14] Afonso, S., Vanore, G. and Batlle, A. (1999) Protoporphyrin IX and oxidative stress. Free Radical Research, 31, 161-170.
[15] Gerschman, R., Gilbert, D., Nye, S.W., Dwyer, P. and Fenn, W.O. (1954) Oxygen poisoning and Xirradiation: A mechanism in common. Science, 119, 623-626.
[16] Bray, R.C., Cockle, S.A., Fielden, E.M., Roberts, P.B., Rotilio, G. and Calabrese, L. (1974) Reduction and inactivation of superoxide dismutase by hydrogen peroxide. Biochemical Journal, 139, 43-48.
[17] Sohal, R.S. and Allen, R.G. (1990) Oxidative stress as a causal factor in differentiation and aging: A unifying hypothesis. Experimental Gerontology, 25, 499-522.
[18] Sohal, R. S., Sohal, B.H. and Brunk, U.T. (1990) Relationship between antioxidant defenses and longevity in different mammalian species. Mechanisms of Ageing and Development, 53, 217-227.
[19] Sohal, R.S., Agarwal, S. and Sohal, B.H. (1995) Oxidative stress and aging in the Mongolian gerbil (Meriones unguiculatus). Mechanisms of Ageing and Development, 81, 15-25.
[20] Helfand, S.L. and Rogina, B. (2003) Genetics of aging in the fruit fly, Drosophila melanogaster. Annual Review of Genetics, 37, 329-348.
[21] Bernard, G.R., Wheeler, A.P., Arons, M.M., Morris, P.E., Paz, H.L., Russell, J.A. and Wright, P.E. (1997) A trial of antioxidants N-acetylcysteine and procysteine in ARDS. The Antioxidant in ARDS Study Group. Chest, 112, 164-172.
[22] Bozuck, A. N. (1972) DNA synthesis in the absence of somatic cell division associated with ageing in Drosophila subobscura. Experimental Gerontology, 7, 147-156.
[23] Ballarini, F., Biaggi, M., Ottolenghi, A. and Sapora, O. (2002) Cellular communication and bystander effects: A critical review for modelling low-dose radiation action. Mutation Research, 501, 1-12.
[24] Sohal, R. S., Donato, H. and Biehl, E. R. (1981) Effect of age and metabolic rate on lipid peroxidation in the housefly, Musca domestica L. Mechanisms of Ageing and Development, 16, 159-167.
[25] Sohal, R.S. and Allen, R.G. (1986) Relationship between oxygen metabolism, aging and development. Advances in Free Radical Biology & Medicine, 2, 117-160.
[26] Orr, W.C. and Sohal, R.S. (1994) Extension of life-span by overexpression of superoxide dismutase and catalase in Drosophila melanogaster. Science, 263, 1128-1130.
[27] Lebovitz, R.M., Zhang, H., Vogel., H., Cartwright, J, Jr., Dionne, L., Lu, N., Huang, S. and Matzuk, M.M. (1996) Neurodegeneration, myocardial injury, and perinatal death in mitochondrial superoxide dismutase-deficient mice. Proceedings of the National Academy of Sciences of the United States of America, 93, 9782-9787.
[28] Duttaroy, A., Paul, A., Kundu, M. and Belton, A. (2003) A Sod2 null mutation confers severely reduced adult lifespan in Drosophila. Genetics, 165, 2295-2299.
[29] Van Remmen, H., Ikeno, Y., Hamilton, M., Pahlavani, M., Wolf, N., Thorpe, S.R., Alderson, N.L., Baynes, J.W., Epstein, C.J., Huang, T.T., Nelson, J., Strong, R. and Richardson, A. (2003) Life-long reduction in MnSOD activity results in increased DNA damage and higher incidence of cancer but does not accelerate aging. Physiological Genomics, 16, 29-37.
[30] Parkes, T.L., Elia, A.J., Dickinson, D., Hilliker, A.J., Phillips, J.P. and Boulianne, G.L. (1998) Extension of Drosophila lifespan by overexpression of human SOD1 in motorneurons. Nature Genetics, 19, 171-174.
[31] Phillips, J.P., Parkes, T.L. and Hilliker, A. J. (2000) Targeted neuronal gene expression and longevity in Drosophila. Experimental Gerontology, 35, 1157-1164.
[32] Sun, J., Molitor, J. and Tower, J. (2004) Effects of simultaneous over-expression of Cu/ZnSOD and MnSOD on Drosophila melanogaster lifespan. Mechanisms of Ageing and Development, 125, 341-349.
[33] Sun, J., Folk, D., Bradley, T.J. and Tower, J., (2002) Induced overexpression of mitochondrial Mn-superoxide dismutase extends the lifespan of adult Drosophila melanogaster. Genetics, 161, 661-672.
[34] Miquel, J., Fleming J. and Economos A.C. (1982) Antioxidants, metabolic rate and aging in Drosophila. Archives of Gerontology and Geriatrics, 1, 159-165.
[35] Bulmer, A. C., Ried, K., Blanchfield, J.T. and Wagner, K.H. (2008) The anti-mutagenic properties of bile pigments. Mutation Research, 658, 28-41.
[36] Odin, A.P. (1997) Antimutagenicity of the porphyrins and non-enzyme porphyrin-containing proteins. Mutation Research, 387, 55-68.
[37] Woodruff, R.C., Phillips, J.P. and Hilliker, A.J. (2004) Increased spontaneous DNA damage in Cu/Zn superoxide dismutase (SOD1) deficient Drosophila. Genome, 47, 1029-1035.
[38] Kirby, K., Jensen, L.T., Binnington, J., Hilliker, A.J., Ulloa, J., Culotta, V.C. and Phillips, J.P. (2008) Instability of superoxide dismutase 1 of Drosophila in mutants deficient for its cognate copper chaperone. The Journal of Biological Chemistry, 283, 35393-35401.
[39] Sun, X., Komatsu, T., Lim, J., Laslo, M., Yolitz, J., Wang, C., Poirier, L., Alberico, T. and Zou, S. (2012) Nutrient-dependent requirement for SOD1 in lifespan extension by protein restriction in Drosophila melanogaster. Aging Cell, 11, 783-793.
[40] Lindsley, D.L. and Zimm, G.G. (1992) The genome of Drosophila melanogaster. Academic Press, La Jolla.
[41] Céspedes-Miranda, E.M., Hernández-Lantigua, I. and Llópiz-Janer, N. (1996) Enzimas que participan como barreras fisiológicas para eliminar los radicales libres: II. Catalasa. Revista Cubana de Investigaciones Biomédicas, 15, 1-7.
[42] Missirlis, F., Rahlfs, S., Dimopoulos, N., Bauer, H., Becker, K., Hilliker, A., Phillips, J.P. and Jackle, H. (2003) A putative glutathione peroxidase of Drosophila encodes a thioredoxin peroxidase that provides resistance against oxidative stress but fails to complement a lack of catalase activity. Biological Chemistry, 384, 463-472.
[43] Addinsoft (2011) XLSTAT. Addinsoft, USA.
[44] Gibson, S.L. and Hilf, R. (1985) Interdependence of fluence, drug dose and oxygen on hematoporphyrin derivative induced photosensitization of tumor mitochondria. Photochemistry and Photobiology, 42, 367-373.
[45] Moan, J. and Sommer, S. (1985) Oxygen dependence of the photosensitizing effect of hematoporphyrin derivative in NHIK 3025 cells. Cancer Research, 45, 1608-1610.
[46] Weishaupt, K.R., Gomer, C.J. and Dougherty, T.J. (1976) Identification of singlet oxygen as the cytotoxic agent in photoinactivation of a murine tumor. Cancer Research, 36, 2326-2329.
[47] Girotti, A.W. (1985) Mechanisms of lipid peroxidation. Journal of Free Radicals in Biology & Medicine, 1, 87-95.
[48] Orr, W.C. and Sohal, R.S. (1992) The effects of catalase gene overexpression on lifespan and resistance to oxidative stress in transgenic Drosophila melanogaster. Archives of Biochemistry and Biophysics, 297, 35-41.
[49] Griswold, C.M., Matthews, A.L., Bewley K.E. and Mahaffey, J.W. (1993) Molecular characterization and rescue of acatalasemic mutants of Drosophila melanogaster. Genetics, 134, 781-788.
[50] Mackay, T.F.C., Lyman, R.F. and Jackson, M.S. (1992) Effects of P-element insertions on quantitative traits in Drosophila melanogaster. Genetics, 130, 315-332.
[51] Boloor, K.K., Kamat, J.P. and Devasagayam, T.P. (2000) Chlorophyllin as a protector of mitochondrial membranes against gamma-radiation and photosensitization. Toxicology, 155, 63-71.
[52] Kamat, J.P., Boloor, K.K and Devasagayam, T.P. (2000) Chlorophyllin as an effective antioxidant against membrane damage in vitro and ex vivo. Biochimica et Biophysica Acta (BBA)—Molecular and Cell Biology of Lipids, 1487, 113-127.
[53] Pimentel, E., Cruces, M.P. and Zimmering, S. (1999) On the persistence of the radioprotective effect of chlorophyllin (CHLN) in somatic cells of Drosophila. Mutation Research, 446, 189-192.
[54] Wolff, S. (1996) Aspects of the adaptive response to very low doses of radiation and other agents. Mutation Research, 358,135-142.

Copyright © 2024 by authors and Scientific Research Publishing Inc.

Creative Commons License

This work and the related PDF file are licensed under a Creative Commons Attribution 4.0 International License.