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Can electrons travel through actin microfilaments and generate oxidative stress in retinol treated Sertoli cell?

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Abstract

In early reports our research group has demonstrated that 7 μM retinol (vitamin A) treatment leads to many changes in Sertoli cell metabolism, such as up-regulation of antioxidant enzyme activities, increase in damage to biomolecules, abnormal cellular division, pre-neoplasic transformation, and cytoskeleton conformational changes. These effects were observed to be dependent on the production of reactive oxygen species (ROS), suggesting extra-nuclear (non-genomic) effects of retinol metabolism. Besides 7 μM retinol treatment causing oxidative stress, we have demonstrated that changes observed in cytoskeleton of Sertoli cells under these conditions were protective, and seem to be an adaptive phenomenon against a pro-oxidant environment resulting from retinol treatment. We have hypothesized that the cytoskeleton can conduct electrons through actin microfilaments, which would be a natural process necessary for cell homeostasis. In the present study we demonstrate results correlating retinol metabolism, actin architecture, mitochondria physiology and ROS, in order to demonstrate that the electron conduction through actin microfilaments might explain our results. We believe that electrons produced by retinol metabolism are dislocated through actin microfilaments to mitochondria, and are transferred to electron transport chain to produce water. When mitochondria capacity to receive electrons is overloaded, superoxide radical production is increased and the oxidative stress process starts. Our results suggested that actin cytoskeleton is essential to oxidative stress production induced by retinol treatment, and electrons conduction through actin microfilaments can be the key of this correlation.

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References

  1. Olson JA (1984) Vitamin A. In: nutrition reviews present knowledge in nutrition, The Nutrition Foundation, Washington DC

  2. Blomhoff R (1994) Overview of vitamin A metabolism and function. In: Vitamin A in health and disease, Marcel Dekker, New York

  3. Blomhoff R, Smeland EB (1994) Role of retinoids in normal hematopoiesis and the immune system. In: Vitamin A in health and disease, Marcel Dekker, New York

  4. Napoli JL (1994) Retinoic acid homeostasis: prospective roles of 13-carotene, retinol, CRBP and CRABP. In: Vitamin A in health and disease, Marcel Dekker, New York

  5. Moreira JCF, Dal-Pizzol F, Guma FCR, Bernard EA (1996) Effects of pre-treatment with hydroxyurea on the increase in [methyl-H-3] thymidine incorporation induced by retinol treatment in Sertoli cells. Med Sci Res 24:383–384

    CAS  Google Scholar 

  6. Moreira JCF, Dal-Pizzol F, VonEndt D, Bernard EA (1997) Effect of retinol on chromatin structure in Sertoli cells: 1,10-phenanthroline inhibit the increased DNAse I sensitivity induced by retinol. Med Sci Res 25:635–638

    Google Scholar 

  7. Moreira JCF, Dal-Pizzol F, Rocha AB, Klamt F, Ribeiro NC, Ferreira CJS, Bernard EA (2000) Retinol-induced changes in the phosphorylation levels of histones and high mobility group proteins from Sertoli cells. Braz J Med Biol Res 33:287–293

    PubMed  CAS  Google Scholar 

  8. Bernard EA, Benfato MS, Moreira JCF (1999) ODC activity in Sertoli cells increased by retinol treatment. Effect mediated by oxygen free radicals. FASEB J 13:A1450–A1450

    Google Scholar 

  9. Klamt F, Dal-Pizzol F, Ribeiro NC, Bernard EA, Benfato MS, Moreira JCF (2000) Retinol-induced elevation of ornithine decarboxylase activity in cultured rat Sertoli cells is attenuated by free radical scavenger and by iron chelator. Mol Cell Biochem 208:71–76

    Article  PubMed  CAS  Google Scholar 

  10. Livrea MA, Packer L (1993) Retinoids—progress in research and clinical applications. Marcel Dekker, New York

    Google Scholar 

  11. Dal-Pizzol F, Klamt F, Benfato MS, Bernard EA, Moreira JCF (2000) Retinol supplementation induces oxidative stress and modulates antioxidant enzime activities in rat Sertoli cells. Free Rad Res 34:395–404

    Article  Google Scholar 

  12. Klamt F, Dal-Pizzol F, Bernard EA, Moreira JCF (2003) Enhanced UV-mediated free radical generation; DNA and mitochondrial damage caused by retinol supplementation. Photochem Photobiol Sci 2:856–860

    Article  PubMed  CAS  Google Scholar 

  13. Dal-Pizzol F, Klamt F, Frota Jr MLC, Moraes LF, Moreira JCF, Benfato MS (2000) Retinol supplementation induces DNA damage and modulates iron turnover in rat Sertoli cells. Free Rad Res 33:677–687

    Article  CAS  Google Scholar 

  14. Dal-Pizzol F, Klamt F, Dalmolin RJS, Bernard EA, Moreira JCF (2001) Mitogenic signaling mediated by oxidants in retinol treated Sertoli cells. Free Rad Res 35:749–755

    Article  CAS  Google Scholar 

  15. Klamt F, Dal-Pizzol F, Roehrs R, de Oliveira RB, Dalmolin R, Henriques JAP, Andrades HHR, Ramos ALLP, Saffi J, Moreira JCF (2003) Genotoxicity, recombinogenicity and cellular preneoplasic transformation induced by Vitamin A supplementation. Mutation Res 539:117–125

    PubMed  CAS  Google Scholar 

  16. de Oliveira RB, Klamt F, Castro MAA, Polydoro M, Zanotto Filho A, Gelain DP, Dal-Pizzol F, Moreira JCF (2005) Morphological and oxidative alterations on Sertoli cells cytoskeleton due to retinol-induced reactive oxygen species. Mol Cell Biochem 271:189–196

    Article  PubMed  CAS  Google Scholar 

  17. Dalle-Donne I, Rossi R, Giustarini D, Gagliano N, Lusini L, Milzani A, di Simplicio P, Colombo R (2001) Actin carbonylation: from a simple marker of protein oxidation to relevant signs of severe functional impairment. Free Radic Biol Med 31:1075–1083

    Article  PubMed  CAS  Google Scholar 

  18. Dalle-Donne I, Rossi R, Giustarini D, Colombo R, Milzani A (2003) Actin S-glutathionylation: evidence against a thiol-disulphide exchange mechanism. Free Radic Biol Med 35:1185–1193

    Article  PubMed  CAS  Google Scholar 

  19. Fujita H, Utsumi T, Muranaka S, Ogino T, Yano H, Akiyama J, Yasuda T, Utsumi K (2005) Involvement of Ras/extracellular signal-regulated kinase, but not Akt pathway in risedronate-induced apoptosis of U937 cells and its suppression by cytochalasin B. Bioche Pharm 69:1773–1784

    Article  CAS  Google Scholar 

  20. Paul C, Manero F, Gonin S, Kretz-Remy C, Virot S, Arrigo AP (2002) Hsp27 as a negative regulator of cytochrome c release. Mol Cell Biol 22:816–834

    Article  PubMed  CAS  Google Scholar 

  21. Yamamoto N, Fukuda K, Matsushita T, Matsukawa M, Hara F, Hamanishi C (2005) Cyclic tensile stretch stimulates the release of reactive oxygen species from osteoblast-like cells. Calcif Tissue Int 76:433–438

    Article  PubMed  CAS  Google Scholar 

  22. Motrescu ER, Otto AM, Brischwein M, Zahler S, Wolf B (2005) Dynamic analysis of metabolic effects of chloroacetaldehyde and cytochalasin B on tumor cells using bioelectronic sensor chips. J. Cancer Res Clin Oncol 131:683–691

    Article  PubMed  CAS  Google Scholar 

  23. Simon VR, Swayne TC, Pon LA (1995) Actin-dependent mitochondrial motility in mitotic yeast and cell-free systems: identification of a more activity on the mitochondrial surface. J Cell Biol 130:345–354

    Article  PubMed  CAS  Google Scholar 

  24. Leterrier JF, Rusakov DA, Nelson BD, Linden M (1994) Interactions between brain mitochondria and cytoskeleton: evidence for specialized outer membrane domains involved in the association of cytoskeleton-associated proteins to mitochondria in situ and in vitro. Microsc Res Tech 27:233–261

    Article  PubMed  CAS  Google Scholar 

  25. Werner E, Werb Z (2002) Integrins engage mitochondrial function for signal transduction by a mechanism dependent on Rho GTPases. J Cell Biol 158:357–368

    Article  PubMed  CAS  Google Scholar 

  26. Pedersen SF, Hoffmann EK, Mills JW (2001) The cytoskeleton and cell volume regulation. Comp Biochem Physiol Part A. 130:385–399

    Article  CAS  Google Scholar 

  27. Levine R, Garland D, Oliver CN (1990) Meth Enzymol 186:464–478

    Google Scholar 

  28. Bradford MA (1976) A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of dye binding. Anal Biochem 72:224–254

    Article  Google Scholar 

  29. Rego AC, Duarte EP, Oliveira CR (1996) Oxidative stress in acidic conditions increases the production of inositol phosphates in chick retinal cells in culture. Free Radic Biol Med 20:175–187

    Article  PubMed  CAS  Google Scholar 

  30. Ellman GL (1959) Tissue sulfhydryl groups. Arch Biochem Biophys 82:70–77

    Article  PubMed  CAS  Google Scholar 

  31. Carmichael J, DeGraff WG, Gazdar AF, Minna JD, Mitchell JB (1987) Evaluation of a tetrazolium-based semiautomated colorimetric assay: assessment of chemosensitivity testing. Cancer Res 47:936–942

    PubMed  CAS  Google Scholar 

  32. Flecha BG, Lessuy S, Boveris A (1991) Hydroperoxide initiated chemiluminescence: an assay for oxidative stress in biopsies of heart, liver and muscle. Free Rad Biol Med 10:93–100

    Article  Google Scholar 

  33. Smiley ST, Reers M, Mottola-Hartshorn C, Lin M, Chen A, Smith TW, Steele Jr G, Chen LB (1991) Intracellular heterogeneity in mitochondrial membrane potential revealed by a J-aggregate-forming lipophilic cation JC-1. Proc Natl Acad Sci USA 88:3671–3675

    Article  PubMed  CAS  Google Scholar 

  34. Wayner DDM, Burton GW, Ingold KU, Locke S (1985) Quantitative measurement of the total, peroxyl radical-trapping antioxidant capability of human blood plasma by controlled peroxidation. FEBS Lett 187:33–37

    Article  PubMed  CAS  Google Scholar 

  35. Halliwell B, Gutteridge JMC (1999) Free radicals in biology and medicine. Oxford University Press, New York

    Google Scholar 

  36. Breitenbach M, Laun P, Gimona M (2005) The actin cytoskeleton, RAS–cAMP signaling and mitochondrial ROS in yeast apoptosis. Trends Cell Biol 15:637–639

    Article  PubMed  CAS  Google Scholar 

  37. Barbu A, Welsh N, Saldeen J (2002) Cytokine-induced apoptosis and necrosis are preceded by disruption of the mitochondrial membrane potential in pancreatic RINm5F cells: prevention by Bcl-2. Mol Cell Endocrinol 190:75–82

    Article  PubMed  CAS  Google Scholar 

  38. Haarer BK, Amberg DC (2004) Old yellow enzyme protects the actin cytoskeleton from oxidative stress. Mol Biol Cell 15:4522–4531

    Article  PubMed  CAS  Google Scholar 

  39. Drewes LR, Horton RW, Betz AL, Gilboe DD (1977) Cytochalasin B inhibition of brain glucose transport and the influence of blood components on inhibitor concentration. Biochim Biophys Acta 471:477–486

    Article  PubMed  CAS  Google Scholar 

  40. Oonk RB, Jansen R, Grootegoed JA (1989) Differential effects of follicle-stimulating hormone, insulin, and insulin-like growth factor I on hexose uptake and lactate production by rat Sertoli cells. J Cell Physiol 139:210–218

    Article  PubMed  CAS  Google Scholar 

  41. Alberts B, Johnson A, Lewis J, Raff M, Roberts K, Walter P (2002) Molecular biology of the cell. Taylor & Francis Group, New York

  42. Gourlay CW, Lindsay NC, Timpson P, Winder SJ, Kathryn RA (2004) A role for the actin cytoskeleton in cell death and ageing in yeast. J Cell Biol 164:803–809

    Article  PubMed  CAS  Google Scholar 

  43. Gourlay CW, Ayscough KR (2005) The actin cytoskeleton in ageing and apoptosis, FEMS Yeast Res 5:1193–1198

    Article  PubMed  CAS  Google Scholar 

  44. Li J, Li Q, Xie C, Zhou H, Wang Y, Zhang N, Shao H, Chan SC, Peng X, Lin S-C, Han J (2004) b-Actin is required for mitochondria clustering and ROS generation in TNF-induced, caspase-independent cell death. J Cell Sci 117:4673–4680

    Article  PubMed  CAS  Google Scholar 

  45. Janmey PA (1998) The cytoskeleton and cell signaling: component localization and mechanical coupling. Physiol Rev 78:763–781

    PubMed  CAS  Google Scholar 

  46. Abram CL, Courtneidge S (2000) Src family tyrosine kinases and growth factor signaling. Exp Cell Res 254:1–13

    Article  PubMed  CAS  Google Scholar 

  47. Blobe GC, Stribling DS, Fabbro D, Stabel S, Hannun YA (1996) Protein kinase C-II specifically binds to and is activated by F-actin. J Biol Chem 271:5823–5830

    Google Scholar 

  48. Prekeris R, Mayhew MW, Cooper JB, Terrian DM (1996) Identification and localization of an actin-binding motif that is unique to the epsilon isoform of protein kinase C and participates in the regulation of synaptic function. J Cell Biol 132:77–90

    Article  PubMed  CAS  Google Scholar 

  49. Imagawa N, Nagasawa K, Nagai K, Kawakami-Honda N, Fujimoto S (2005) Protein kinase C-independent pathway for NADPH oxidase activation in guinea pig peritoneal polymorphonuclear leukocytes by cytochalasin D. Arch Biochem Biophys 438:119–124

    Article  PubMed  CAS  Google Scholar 

  50. Nelson DL, COX MM (2000) Lehninger principles of biochemistry, Worth Publishers Inc, New York

    Google Scholar 

  51. Papakonstanti EA, Stournaras C (2002) Association of PI-3 kinase with PAK1 leads to actin phosphorylation and cytoskeletal reorganization. Mol Biol Cell 13:2946–2962

    Article  PubMed  CAS  Google Scholar 

  52. Jungbluth A, von Arnim V, Biegelmann E, Humbel B, Schweiger A, Gerisch G (1994) Strong increase in the tyrosine phosphorylation of actin upon inhibition of oxidative phosphorylation: correlation with reversible rearrangements in the actin skeleton of Dictyostelium cells. J Cell Sci 107:117–125

    PubMed  CAS  Google Scholar 

  53. Jungbluth A, Eckerskorn C, Gerisch G, Lottspeich F, Stocker S, Schweiger A (1995) Stress-induced tyrosine phosphorylation of actin in Dictyostelium cells and localization of the phosphorylation site to tyrosine-53 adjacent to the DNase I binding loop. FEBS Lett 375:87–90

    Article  PubMed  CAS  Google Scholar 

  54. T’Jampens D, Bailey J, Cook LJ, Constantin B, Vandekerckhove J, Gettemans J (1999) Physarum amoebae express a distinct fragmin-like actin-binding proteinthat controls in vitro phosphorylation of actin by the actin-fragmin kinase. Eur J Biochem 265:240–250

    Article  PubMed  CAS  Google Scholar 

  55. Cavelier G (2000) Theory of malignant cell transformation by superoxide fate coupled with cytoskeletal electron-transport and electron-transfer. Med Hyp 54:95–98

    Article  CAS  Google Scholar 

  56. Schrenzel J, Serrander L, Bánfi B, Nübe O, Fouyouzi R, Lew DP, Demaurex N, Krause KH (1998) Electron currents generated by the human phagocyte NADPH oxidase. Nature 392:734–737

    Article  PubMed  CAS  Google Scholar 

  57. Xiong Y, Shi L, Chen B, Mayer MU, Lower BH, Londer Y, Bose S, Hochella MF, Fredrickson JK, Squier TC (2006) High-affinity binding and direct electron transfer to solid metals by the Shewanella oneidensis MR-1 outer membrane c-type cytochrome OmcA. J Am Chem Soc 128:13978–13979

    Article  PubMed  CAS  Google Scholar 

  58. Gartzkel J, Lange K (2002) Cellular target of weak magnetic fields: ionic conduction along actin filaments of microvilli. Am J Physiol Cell Physiol 283:C1333–C1346

    Google Scholar 

  59. Calaghana SC, Le Guennecb JY, White E (2004) Cytoskeletal modulation of electrical and mechanical activity in cardiac myocytes. Progr Biophys Mol Biol 84:29–59

    Article  CAS  Google Scholar 

  60. Bengtsson T, Orselius K, Wettero J (2006) Role of the actin cytoskeleton during respiratory burst in chemoattractant-stimulated neutrophils. Cell Biol Int 30:154–163

    Article  PubMed  CAS  Google Scholar 

  61. Boldogh IR, Pon LA (2006) Interactions of mitochondria with the actin cytoskeleton. Biochim Biophys Acta 1763:450–462

    Article  PubMed  CAS  Google Scholar 

  62. Gourlay CW, Ayscough KR (2005) Identification of an upstream regulatory pathway controlling actin-mediated apoptosis in yeast. J Cell Sci 118:2119–2132

    Article  PubMed  CAS  Google Scholar 

  63. Anesti V, Scorrano L (2006) The relationship between mitochondrial shape and function and the cytoskeleton. Biochimica et Biophysica Acta 1757:692–699

    Article  PubMed  CAS  Google Scholar 

  64. Breitenbach M, Laun P, Gimona M (2005) The actin cytoskeleton, RAS–cAMP signaling and mitochondrial ROS in yeast apoptosis. Trends Cell Biol 15:637–639

    Article  PubMed  CAS  Google Scholar 

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Correspondence to Ramatis Birnfeld de Oliveira.

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de Oliveira, R.B., de Bittencourt Pasquali, M.A., Filho, A.Z. et al. Can electrons travel through actin microfilaments and generate oxidative stress in retinol treated Sertoli cell?. Mol Cell Biochem 301, 33–45 (2007). https://doi.org/10.1007/s11010-006-9394-1

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