Kelvin J. A. Davies, Ph.D., D.Sc.
James E. Birren Professor of Gerontology,
and Professor of Molecular & Computational Biology.
Regulation of gene expression in oxidative stress; degradation of oxidatively damaged proteins by the Proteasome and the mitochondrial Lon protease; adaptive responses to oxidative stress; apoptosis, necrosis, and mitoptosis in oxidative stress; role of oxidative stress, and stress resistance, in the aging process.

Publications

1. Davies, K.J.A., Packer, L., and Brooks, G.A. (1981) Biochemical adaptation of mitochondria, muscle, and whole-animal respiration to endurance training. Arch. Biochem. Biophys. 209, 539-554.

2. Davies, K.J.A., Packer, L., and Brooks, G.A. (1982) Exercise Bioenergetics following sprint training. Arch. Biochem. Biophys. 215, 260-265.

3. Maguire, J.J., Davies, K.J.A., Dallman, P.R., and Packer, L. (1982) Effects of dietary iron deficiency on iron-sulfur proteins and bioenergetic functions of skeletal muscle mitochondria. Biochim. Biophys. Acta 679, 210-220.

4. Davies, K.J.A., Maguire, J.J., Brooks, G.A., Dallman, P.R., and Packer, L. (1982) Muscle mitochondrial bioenergetics, oxygen supply, and work capacity during dietary iron deficiency and repletion. Am. J. Physiol.: Endocrinol. Metab. 242, E418-E427.

5. Quintanilha, A.T. and Davies, K.J.A. (1982) Vitamin E deficiency and photosensitization of electron transport carriers in microsomes. FEBS Lett. 139, 241-244.

6. Quintanilha, A.T., Packer, L., Davies, J.M.S.,Racanelli, T.L. and Davies, K.J.A. (1982) Membrane effects of vitamin E deficiency: bioenergetic and surface charge density studies of skeletal muscle and liver mitochondria. Ann. NY Acad. Sci. 393, 32-47.

7. Davies, K.J.A., Quintanilha, A.T., Brooks, G.A., and Packer, L. (1982) Free radicals and tissue damage produced by exercise. Biochem. Biophys. Res. Commun. 107, 1198-1205.

8. Davies, K.J.A. and Hochstein, P. (1982) Ubisemiquinone radicals in liver: implications for a mitochondrial Q cycle in vivo. Biochem. Biophys. Res. Commun. 107, 1292-1299.

9. Davies, K.J.A., Doroshow, J.H., and Hochstein, P. (1983) Mitochondrial NADH dehydrogenase-catalyzed oxygen radical production by adriamycin, and the relative inactivity of 5-iminodaunorubicin. FEBS Lett. 153, 227-230.

10. Doroshow, J.H. and Davies, K.J.A. (1983) Comparative cardiac oxygen radical metabolism by anthracycline antibiotics, mitoxantrone, bisantrene, 4'-(9-acridinylamino)-methanesulfon-m-anisidide, and neocarzino- statin. Biochem. Pharmacol. 32, 2935-2939.

11. Davies, K.J.A., Donovan, C.M., Refino, C.J., Brooks, G.A., Packer, L., and Dallman, P.R. (1984) Distinguishing the effects of anemia and muscle iron deficiency on exercise bioenergetics in the rat. Am. J. Physiol.: Endocrinol. Metab. 246, E535-E543.

12. Sevanian, A., Davies, K.J.A. and Hochstein, P. (1985) Conservation of vitamin C by uric acid in blood. J. Free Radicals Biol. Med. 1, 117-124.

13. Davies, K.J.A. and Doroshow, J.H. (1986) Redox cycling of anthracyclines by cardiac mitochondria: I. Anthracycline radical formation by NADH dehydrogenase. J. Biol. Chem. 261, 3060-3067.

14. Doroshow, J.H. and Davies, K.J.A. (1986) Redox cycling of anthracyclines by cardiac mitochondria: II. Formation of superoxide anion, hydrogen peroxide, and hydroxyl radical. J. Biol. Chem.261, 3068-3074.

15. Davies, K.J.A., Sevanian, A., Muakkassah-Kelly, S.F., and Hochstein, P. (1986) Uric acid-iron complexes: a new aspect of the antioxidant functions of uric acid. Biochem. J. 235, 747-754.

16. Davies, K.J.A. (1986) Intracellular proteolytic systems may function as secondary antioxidant defenses: An hypothesis. J. Free Radicals Biol. Med. 2, 155-173.

17. Davies, K.J.A. and Goldberg, A.L. (1987) Oxygen radicals stimulate proteolysis and lipid peroxidation by independent mechanisms in erythrocytes. J. Biol. Chem. 262, 8220-8226.

18. Davies, K.J.A. and Goldberg, A.L. (1987) Proteins damaged by oxygen radicals are rapidly degraded in extracts of red blood cells. J. Biol. Chem. 262, 8227-8234.

19. Davies, K.J.A. (1987) Protein damage and degradation by oxygen radicals: I. general aspects. J. Biol.Chem. 262, 9895-9901.

20. Davies, K.J.A., Delsignore, M.E., and Lin, S.W. (1987) Protein damage and degradation by oxygen radicals: II. Modification of amino acids. J. Biol. Chem. 262, 9902-9907.

21. Davies, K.J.A. and Delsignore, M.E. (1987) Protein damage and degradation by oxygen radicals: III. Modification of secondary and tertiary structure. J. Biol. Chem. 262, 9908-9913. 5

22. Davies, K.J.A., Lin, S.W., and Pacifici, R.E. (1987) Protein damage and degradation by oxygen radicals: IV. Degradation of denatured protein. J. Biol. Chem. 262, 9914-9920.

23. Taylor, A. and Davies, K.J.A. (1987) Protein oxidation and diminished proteolytic capacity in cataract formation during aging. Free Radical Biol. Med. 3, 371-377.

24. Davies, K.J.A. and Lin, S.W. (1988) Degradation of oxidatively denatured proteins in Escherichia coli. Free Radical Biol. Med. 5, 215-223.

25. Davies, K.J.A. and Lin, S.W. (1988) Oxidatively denatured proteins are degraded by an ATP-independent pathway in Escherichia coli. Free Radical Biol. Med. 5, 225-236.

26. McKenna, S.M. and Davies, K.J.A. (1988) Inhibition of bacterial growth by hypochlorous acid. Biochem. J.. 254, 685-692.

27. Salo, D.C., Lin, S.W., Pacifici, R.E., and Davies, K.J.A. (1988) Superoxide dismutase is preferentially degraded by a proteolytic system from red blood cells following oxidative modification by hydrogen peroxide. Free Radical Biol. Med. 5, 335-339.

28. Marcillat, O., Zhang, Y., Lin, S.W., and Davies, K.J.A. (1988) Mitochondria contain a proteolytic system which can recognize and degrade oxidatively denatured proteins. Biochem. J. 254, 677-683.

29. Marcillat, O., Zhang, Y., and Davies, K.J.A. (1989) Oxidative and non-oxidative mechanisms in the inactivation of cardiac mitochondrial electron transport chain components by doxorubicin. Biochem. J. 259, 181-189.

30. Pacifici, R.E., Salo, D.C., Lin, S.W., and Davies, K.J.A. (1989) Macroxyproteinase (M.O.P.): A 670 kDa proteinase complex that degrades oxidatively denatured proteins in red blood cells. Free Radical Biol. Med. 7, 521-536.

31. Murakami, K., Jahngen, J.H., Lin, S.W., Davies, K.J.A., and Taylor, A. (1990) Degradation of eye lens alpha-crystallin by a lens high molecular weight proteinase following exposure to hydroxyl radicals. Free Radical Biol. Med. 8, 217-222.

32. Pacifici, R.E. and Davies, K.J.A. (1990) Protein degradation as an index of oxidative stress. Methods Enzymol. 186, 485-502.

33. Salo, D.C., Pacifici, R.E., and Davies, K.J.A. (1990) Superoxide dismutase undergoes proteolysis and fragmentation following oxidative modification and inactivation. J. Biol. Chem. 265, 11919-11927.

34. Zhang, Y., Marcillat, O., Giulivi, C., Ernster, L., and Davies, K.J.A. (1990) The oxidative inactivation of mitochondrial electron transport chain components and ATPase. J. Biol. Chem. 265, 16330-16336.

35. Giulivi, C. and Davies, K.J.A. (1990) A novel antioxidant role for hemoglobin: the comproportionation of ferrylhemoglobin with oxyhemoglobin. J. Biol. Chem. 265, 19453-19460.

36. Pacifici, R.E. and Davies, K.J.A. (1991) Protein, lipid, and DNA repair systems in oxidative stress: the free radical theory of aging revisited. Gerontology 37, 166-180.

37. Salo, D.C., Donovan, C.M., and Davies, K.J.A. (1991) HSP70 and other possible heat shock or oxidative stress proteins are induced in skeletal muscle, heart, and liver during exercise. Free Radical Biol. Med. 11, 239-246.

38. Maiorino, M., Chu, F.F., Ursini, F., Davies, K.J.A., Doroshow, J.H., and Esworthy, R.S. (1991) Phospholipid hydroperoxide glutathione peroxidase is the 18-kDa selenoprotein expressed in human tumor cell lines. J. Biol. Chem. 266, 7728-7732.

39. Sevanian, A., Davies, K.J.A., and Hochstein, P. (1991) Serum urate as an antioxidant for ascorbic acid. Am. J. Clin. Nutr. 54, 1129S-1134S.

40. Giulivi, C. and Davies, K.J.A. (1993) Dityrosine and tyrosine oxidation products are endogenous markers for the selective proteolysis of oxidatively modified red blood cell hemoglobin by the (19 S) proteasome. J. Biol. Chem. 268, 8752-8759.

41. Davies, K.J.A. (1993) Protein modification by oxidants and the role of proteolytic enzymes. Biochem. Soc. Trans. 21, 346-353.

42. Pacifici, R.E., Kono, Y., and Davies, K.J.A. (1993) Hydrophobicity as the signal for selective degradation of hydroxyl radical modified hemoglobin by the multicatalytic proteinase complex, proteasome. J. Biol. Chem. 268, 15405-15411.

43. Davies, J.M.S., Horwitz, D.M., and Davies, K.J.A. (1993) Potential roles of hypochlorous acid and N-chloroamines in collagen breakdown by phagocytic cells in synovitis. Free Radical Biol. Med. 15, 637-643.

44. Giulivi, C., Hochstein, P., and Davies, K.J.A. (1994) Hydrogen peroxide production by red blood cells. Free Radical Biol. Med. 16, 123-129.

45. Giulivi, C. and Davies, K.J.A. (1994) Hydrogen peroxide-mediated ferrylhemoglobin generation in vitro and in red blood cells. Methods in Enzymology: Hemoglobins, Part B 231, 490-496.

46. Davies, J.M.S., Horwitz, D.M., and Davies, K.J.A. (1994) Inhibition of collagenase activity by N-chlorotaurine, a product of activated neutrophils. Arthritis & Rheumatism 37, 424-427. 6

47. Giulivi, C. and Davies, K.J.A. (1994) Dityrosine: a marker for oxidatively modified proteins and selective proteolysis. Methods in Enzymology: Oxygen Radicals in Biological Systems, Part C 233, 363-371.

48. Giulivi, C., Pacifici, R.E., and Davies, K.J.A. (1994) Exposure of hydrophobic moieties promotes the selective degradation of hydrogen peroxide-modified hemoglobin by the multicatalytic proteinase complex, proteasome. Arch. Biochem. Biophys. 311, 329-341.

49. Crawford, D.R., Edbauer-Nechamen, C., Lowry, C.V., Salmon, S.L., Kim, Y.K., Davies, J.M.S., and Davies, K.J.A. (1994) Assessing gene expression during oxidative stress. Methods in Enzymology: Oxygen Radicals in Biological Systems, Part D 234, 175-217.

50. Crawford, D.R. and Davies, K.J.A. (1994) Adaptive response and oxidative stress. Environmental. Health Perspectives. 102 (Suppl. 10), 25-28

51. Grune, T., Reinheckel, T., and Davies, K.J.A. (1995) Protein degradation in cultured liver epithelial cells during oxidative stress: role of the multicatalytic proteinase complex, proteasome. J. Biol. Chem. 270, 2344-2351.

52. Davies, J.M.S., Lowry, C.V., and Davies, K.J.A. (1995) Transient adaptation to oxidative stress in yeast. Arch. Biochem. Biophys. 317, 1-6.

53. Wiese, A.G., Pacifici, R.E., and Davies, K.J.A. (1995) Transient adaptation to oxidative stress in mammalian cells. Arch. Biochem. Biophys 318, 231-240.

54. Davies, K.J.A. (1995) Oxidative Stress: the paradox of aerobic life. Biochem. Soc. Symp. 61, 1-31.

55. Crawford, D.R., Schools, G.P., Salmon, S.L., and Davies, K.J.A. (1996) Hydrogen peroxide induces the expression of adapt15, a novel RNA associated with polysomes in hamster HA-1 cells. Arch. Biochem. Biophys. 325, 256-264.

56. Pryor, W.A. and Davies, K.J.A. (1996) The birth and adolescence of the Gordon Conference on oxygen radicals in biology. Free Radical Biol. Med. 20, vii-xxii.

57. Crawford, D.R., Schools, G.P., and Davies, K.J.A. (1996) Oxidant-inducible adapt15 is associated with growth arrest and DNA damage-inducible gadd153 and gadd45. Arch. Biochem. Biophys. 329, 137-144.

58. Grune, T., Reinheckel, T., Talbot, M., and Davies, K.J.A. (1996) Degradation of oxidized proteins in K562 human K-562 hematopoietic cells by proteasome. J. Biol. Chem. 271, 15504-15509.

59. Melendez, J.A. and Davies, K.J.A. (1996) Manganese superoxide dismutase modulates interleukin 1a levels in HT -1080 fibrosarcoma cells. J. Biol. Chem. 271, 18898-18903.

60. Crawford, D.R., Leahy, K.P., Wang, Y., Schools, G.P., Kochheiser, J.C. and Davies, K.J.A. (1996) Oxidative stress induces the levels of a mafG homolog in Hamster HA-1 cells. Free Radical Biol. Med., 21, 521-525.

61. Wang, Y., Crawford, D.R., and Davies, K.J.A. (1996) Adapt33, a novel oxidant-inducible RNA from Hamster HA-1 cells. Arch. Biochem. Biophys. 332, 255-260.

62. Crawford, D.R., Wang, Y., Schools, G.P., Kochheiser, J., and Davies, K.J.A. (1997) Down-regulation of mammalian mitochondrial RNA’s during oxidative stress. Free Radical Biol. Med. 22, 551-559

63. Crawford, D.R., Lauzon, R.J., Wang, Y., Mazurkiewicz, J.E., Schools, G.P., and Davies, K.J.A. (1997) 16S mitochondrial ribosomal RNA degradation is associated with apoptosis. Free Radical Biol. Med. 22, 1295-1300.

64. Crawford, D.R. and Davies, K.J.A. (1997) Modulation of a cardiogenic shock inducible RNA by chemical stress: adapt73/PigHep3. Surgery 121, 581-587.

65. Grune, T., Reinheckel, T., and Davies, K.J.A. (1997) Degradation of oxidized proteins in mammalian cells. FASEB. J. 11, 526-534.

66. Crawford, D.R., Leahy, K.P., Abramova, N., Lan, L., Wang, Y., and Davies, K.J.A. (1997) Hamster adapt78, mRNA is a Down Syndrome critical region homologue that is inducible by oxidative stress. Arch. Biochem. Biophys. 342, 6-12.

67. Grune, T. and Davies, K.J.A. (1997) Breakdown of oxidized proteins as a part of secondary antioxidant defenses in mammalian cells. Biofactors. 6, 165-172.

68. Sertil, O., Cohen, B., Davies, K.J.A., and Lowry, C.V. (1997) The DAN1 gene of S. Cerevisiae is regulated in parallel with the hypoxic genes, but by a different mechanism. GENE. 192, 199-205.

69. Grune, T., Blasig, I.E., Sitte, N., Roloff, B., Haseloff, R., and Davies, K.J.A. (1998) Peroxynitrite increases the degradation of aconitase and other cellular proteins by proteasome. J. Biol. Chem. 273, 10857-10862.

70. Crawford, D.A., Abramova, N.E., and Davies, K.J.A. (1998) Oxidative stress causes a general, calcium dependent degradation of mitochondrial polynucleotides. Free Radical Biol. Med. 25, 1106-1111.

71. Reinheckel, T., Sitte, N., Ulrich, O., Kuckelkorn, U., Grune, T., and Davies, K.J.A. (1998) Comparative resistance of the 20S and 26S proteasome to oxidative stres. Biochem. J. 335, 637-642.

72. Ullrich, O., Sitte, N., Sommerburg, O., Sandig, V., Davies, K.J.A., and Grune, T. (1999) Influence of DNA binding on the degradation of oxidized histones by the 20S proteasome. Arch. Biochem. Biophys. 362: 211-216. 7

73. Ullrich, O., Reinheckel, T., Sitte, N., Haass, G., Grune, T., and Davies, K.J.A. (1999) Poly-ADP-ribose-polymerase activates nuclear proteasome to degrade oxidatively damaged histones. Proc. Natl. Acad. Sci. ( USA) 96, 6223-6228, 1999.

74. Davies, K.J.A. (1999) The broad spectrum of responses to oxidants in proliferating cells: A new paradigm for oxidative stress. IUBMB Life 48, 41-47.

75. Leahy, K.P., Davies, K.J.A., Dull, M., Kort, J.J., Lawrence, K.W., and Crawford, D.A. (1999) Adapt78, a stressinducible mRNA, is related to the glucose-regulated family of genes. Arch. Biochem. Biophys. 368, 67-74.

76. Melendez, J.A., Melathe, R.P., Rodriguez, A.M., Mazurkiewicz, J.E., and Davies, K.J.A. (1999) Nitric oxide enhances the manganese superoxide dismutase dependent suppression of proliferation in HT -1080 fibrosarcoma cells. Cell Growth and Differentiation. 10, 655-664.

77. Abramova, N.E., Davies, K.J.A., and Crawford, D.R. (2000) Polynucleotide degradation during early stage response to oxidative stress is specific to mitochondria. Free Radic. Biol. Med. 28, 281-288.

78. Sitte, N., Huber, M., Grune, T., Ladhoff, A., Doecke, W.-D., von Zglinicki, T., and Davies, K.J.A. (2000) Proteasome inhibition by lipofuscin/ceroid during postmitotic aging of fibroblasts. FASEB J. 14, 1490-1498.

79. Sitte, N., Merker, K., von Zglinicki, T., Grune, T., and Davies, K.J.A. (2000) Protein oxidation and degradation during cellular senescence of BJ -Fibroblasts: Part I effects of proliferative senescence. FASEB J. 14, 2495-2502.

80. Sitte, N., Merker, K., von Zglinicki, T., Davies, K.J.A., and Grune, T. (2000) Protein oxidation and degradation during cellular senescence of BJ -Fibroblasts: Part II aging of non-dividing cells FASEB J. 14, 2503-2510.

81. Cadenas, E. and Davies, K.J.A. (2000) Mitochondrial free radical production, oxidative stress, and aging. Free Radic. Biol. Med. 29, 222-2230.

82. Shringarpure, R., Grune, T., Sitte, N., and Davies, K.J.A. (2000) 4-Hydroxynonenal-modified amyloid-ß peptide inhibits the proteasome: possible importance in Alzheimer’s disease. Cell Mol. Life Sci. 57, 1802-1809,

83. Davies, K.J.A. (2000) An overview of oxidative stress. IUBMB Life 50, 1-4.

84. Davies, K.J.A. (2000) Oxidative stress, antioxidant defenses, and damage removal, repair, and replacement systems. IUBMB Life 50,279-289.

85. Davies, K.J.A. (2001) Degradation of oxidized proteins by the 20S proteasome. Biochimie 83, 301-310.

86. Demasi, M., Shringarpure, R., and Davies, K.J.A. (2001) Glutathiolation of the proteasome is enhanced by proteolytic inhibitors. Arch. Biochem. Biophys. 389, 254-263.

87. Grune, T., Shringarpure, R., Sitte, N., and Davies, K.J.A. (2001) Age-related changes in protein oxidation and proteolysis in mammalian cells. J. Gerontol.: Biol. Sci. 56A, B459-B467.

88. Giulivi, C. and Davies, K.J.A. (2001) Mechanism of the formation and proteolytic release of H2O2 -induced dityrosine and tyrosine oxidation products in hemoglobin and red blood cells. J. Biol. Chem. 276, 24129-24136.

89. Bota, D.A. and Davies, K.J.A. (2001) Protein degradation in mitochondria: Implications for oxidative stress, aging, and disease.; a novel etiological classification of mitochondrial proteolytic disorders. Mitochondrion 1, 33-49.

90. Abramova, N.E., Cohen, B.D., Sertil, O., Kapoor, R., Davies, K.J.A, and Lowry, C.V. (2001) Regulatory mechanisms controlling expression of the DAN/TIR mannoprotein genes during anaerobic remodeling of the cell wall in Saccharomyces cerevisiae. Genetics 157, 1169-1177.

91. Cohen, B.D., Sertil, O, Abramova, N.E., Davies, K.J.A, and Lowry, C.V. (2001) Induction and repression of DAN1 and the family of anaerobic mannoprotein genes in Saccharomyces cerevisiae occurs through a complex array of regulatory sites. Nucleic Acids Res. 29, 799-808.

92. Davies, K.J.A. and Ermak, G. (2001) The essential role of calcium in induction of the DSCR1 (Adapt78) gene. BioFactors 12, 1-3.

93. Ermak, G., Morgan, T.E., and Davies, K.J.A. (2001) Chronic overexpression of the calcineurin inhibitory gene DSCR1 (Adapt78 ) is associated with Alzheimer’s disease. J. Biol. Chem. 276, 38787-38794.

94. Shringarpure, R., Grune, T., and Davies, K.J.A. (2001) Protein oxidation and 20S proteasome-dependent proteolysis in mammalian cells. Cell Mol. Life Sci. 58, 1442-1450.

95. Ermak, G., Harris, C., and Davies, K.J.A. (2002) Calcium and oxidative stress: from cell signaling to cell death. Mol. Immunol. 38, 713-721.

96. Grune, T., Reinheckel, T., Li, R., North, J.A., and Davies, K. J.A. (2002) Proteasome-dependent turnover of protein disulfide isomerase in oxidatively stressed cells. Arch. Biochem. Biophys. 397, 407-413.

97. Ermak, G., Harris, C., and Davies, K.J.A. (2002) The DSCR1 (Adapt78) Isoform 1 protein, ACalcipressin 1" inhibits 8 calcineurin and protects against acute calcium-mediated stress damage, including transient oxidative stress. FASEB J. In Press.

98. Shringarpure, R., Grune, T., and Davies, K.J.A. (2002) Protein turnover by the proteasome in aging and disease. Free Radic. Biol. Med. In Press.

99. Crawford, D.R., Kochheiser, J.C., Schools, G.P., Salmon, S.L., and Davies, K.J.A. (2002) Differential display: A critical analysis Gene Expression in press.

100. Grune, T., Reinheckel, T., North, J.A., Li, R., Bescos, P.B., Shringarpure, R., and Davies, K.J.A. Ezrin turnover and cell shape changes catalyzed by proteasome in oxidatively stressed cells. FASEB J. Submitted.

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