1,25-Dihydroxyvitamin D3 increases the toxicity of hydrogen peroxide in the human monocytic line U937: the role of calcium and heat shock

1,25-dihydroxyvitamin D3 (1,25-(OH)2D3) increases synthesis of heat shock proteins in monocytes and U937 cells and protects these cells from thermal injury. We examined whether 1,25-(OH)2D3 would also modulate the susceptibility of U937 cells to H2O2-induced oxidative stress. Cell viability was assessed by trypan blue exclusion and [3H]thymidine incorporation into DNA. Prior incubation for 24 h with 1,25-(OH)2D3 (25 pM or higher) unexpectedly increased H2O2 toxicity. Since cellular Ca2+ may be a mediator of cell injury we investigated effects of altering extracellular Ca2+ ([Ca2+]e) on 1,25-(OH)2D3- enhanced H2O2 toxicity as well as effects of 1,25-(OH)2D3 and H2O2 on cytosolic free Ca2+ concentration ([Ca2+]f). Basal [Ca2+]f in medium containing 1.5 mM Ca as determined by fura-2 fluorescence was higher in 1,25-(OH)2D3-pretreated cells than control cells (137 versus 112 nM, P less than 0.005). H2O2 induced a rapid increase in [Ca2+]f (to greater than 300 nM) in both 1,25-(OH)2D3-treated and control cells, which was prevented by a reduction in [Ca2+]e to less than basal [Ca2+]f. The 1,25(OH)2D3-induced increase in H2O2 toxicity was also prevented by preincubation with 1,25-(OH)2D3 in Ca2+-free medium or by exposing the cells to H2O2 in the presence of EGTA. Preexposure of cells to 45 degrees C for 20 min, 4 h earlier, partially prevented the toxic effects of H2O2 particularly in 1,25-(OH)2D3-treated cells, even in the presence of physiological levels of [Ca2+]e. Thus 1,25-(OH)2D3 potentiates H2O2-induced injury probably by increasing cellular Ca2+ stores. The 1,25-(OH)2D3-induced amplification of the heat shock response likely represents a mechanism for counteracting the Ca2+- associated enhanced susceptibility to oxidative injury due to 1,25- (OH)2D3.

[1]  J. Chisholm,et al.  Modulation by 1,25-dihydroxycholecalciferol of the acute change in cytosolic free calcium induced by thyrotropin-releasing hormone in GH4C1 pituitary cells. , 1988, The Journal of clinical investigation.

[2]  M. Thomasset,et al.  Transcriptional and post-transcriptional regulation of vitamin D-dependent calcium-binding protein gene expression in the rat duodenum by 1,25-dihydroxycholecalciferol. , 1987, The Journal of biological chemistry.

[3]  T. Reimers,et al.  Calbindin-D in peripheral nerve cells is vitamin D and calcium dependent. , 1987, Proceedings of the National Academy of Sciences of the United States of America.

[4]  M. Lieberherr.  Effects of vitamin D3 metabolites on cytosolic free calcium in confluent mouse osteoblasts. , 1987, The Journal of biological chemistry.

[5]  H. DeLuca,et al.  Molecular cloning of the cDNA and chromosomal gene for vitamin D-dependent calcium-binding protein of rat intestine. , 1987, Proceedings of the National Academy of Sciences of the United States of America.

[6]  S. Krane,et al.  Hormone 1 alpha,25-dihydroxyvitamin D3 modulates heat shock response in monocytes. , 1987, The American journal of physiology.

[7]  M. Haussler,et al.  Molecular cloning of complementary DNA encoding the avian receptor for vitamin D. , 1987, Science.

[8]  A. Norman,et al.  Regulation of calbindin-D28K gene expression by 1,25-dihydroxyvitamin D3 is correlated to receptor occupancy. , 1986, The Journal of biological chemistry.

[9]  A. Campbell,et al.  Intracellular Ca2+ and cell injury: a paradoxical role of Ca2+ in complement membrane attack. , 1986, Cell calcium.

[10]  J. Bonventre,et al.  Mechanism of calcium potentiation of oxygen free radical injury to renal mitochondria. A model for post-ischemic and toxic mitochondrial damage. , 1986, The Journal of biological chemistry.

[11]  S. Munro,et al.  An hsp70-like protein in the ER: Identity with the 78 kd glucose-regulated protein and immunoglobulin heavy chain binding protein , 1986, Cell.

[12]  J. Cheung,et al.  Vasopressin increases cytosolic free calcium concentration in glomerular mesangial cells. , 1986, The American journal of physiology.

[13]  K. Lanks,et al.  Modulators of the eukaryotic heat shock response. , 1986, Experimental Cell Research.

[14]  G. Hahn,et al.  Rapid increases in inositol trisphosphate and intracellular Ca++ after heat shock. , 1986, Biochemical and biophysical research communications.

[15]  D. Baran,et al.  1,25 Dihydroxyvitamin D increases hepatocyte cytosolic calcium levels. A potential regulator of vitamin D-25-hydroxylase. , 1986, The Journal of clinical investigation.

[16]  A. Goldberg,et al.  Abnormal proteins serve as eukaryotic stress signals and trigger the activation of heat shock genes. , 1986, Science.

[17]  S. Lindquist,et al.  RNA splicing is interrupted by heat shock and is rescued by heat shock protein synthesis , 1986, Cell.

[18]  S. Krane,et al.  Differential effects of 1,25-dihydroxyvitamin D3 on human lymphocytes and monocyte/macrophages: inhibition of interleukin-2 and augmentation of interleukin-1 production. , 1986, Cellular immunology.

[19]  S. Krane,et al.  1,25-Dihydroxyvitamin D3 maintains adherence of human monocytes and protects them from thermal injury. , 1986, The Journal of clinical investigation.

[20]  M. Cohen,et al.  1,25-Dihydroxyvitamin D3 activates secretion of hydrogen peroxide by human monocytes. , 1986, Journal of immunology.

[21]  J. Dayer,et al.  Effect of interferon-γ and 1α,25-dihydroxyvitamin D3 on superoxide anion, prostaglandins E2, and mononuclear cell factor production by U937 cells , 1986 .

[22]  H. Pelham,et al.  Involvement of ATP in the nuclear and nucleolar functions of the 70 kd heat shock protein. , 1985, The EMBO journal.

[23]  J. Landry,et al.  Inhibition of the heat shock response and synthesis of glucose-regulated proteins in Ca2+-deprived rat hepatoma cells. , 1985, Biochemical and biophysical research communications.

[24]  B. Ames,et al.  Positive control of a regulon for defenses against oxidative stress and some heat-shock proteins in Salmonella typhimurium , 1985, Cell.

[25]  R. Tsien,et al.  A new generation of Ca2+ indicators with greatly improved fluorescence properties. , 1985, The Journal of biological chemistry.

[26]  S. Krane,et al.  1 alpha,25-dihydroxyvitamin D3 induces maturation of the human monocyte cell line U937, and, in association with a factor from human T lymphocytes, augments production of the monokine, mononuclear cell factor. , 1984, The Journal of clinical investigation.

[27]  S. Krane,et al.  Specific high-affinity receptors for 1,25-dihydroxyvitamin D3 in human peripheral blood mononuclear cells: presence in monocytes and induction in T lymphocytes following activation. , 1983, The Journal of clinical endocrinology and metabolism.

[28]  P. Reitsma,et al.  Induction of monocytic differentiation and bone resorption by 1,25-dihydroxyvitamin D3. , 1983, Proceedings of the National Academy of Sciences of the United States of America.

[29]  K. Colston.  Vitamin D: Chemical, Biochemical and Clinical Endocrinology of Calcium Metabolism , 1983 .

[30]  S. Manolagas,et al.  1,25-dihydroxyvitamin D3 receptors in human leukocytes. , 1983, Science.

[31]  L. Orci,et al.  The vitamin D endocrine system: steroid metabolism, hormone receptors, and biological response (calcium binding proteins). , 1982, Endocrine reviews.

[32]  J. Farber,et al.  Calcium dependence of toxic cell death: a final common pathway. , 1979, Science.

[33]  C. Nathan,et al.  Extracellular cytolysis by activated macrophages and granulocytes. I. Pharmacologic triggering of effector cells and the release of hydrogen peroxide , 1979, The Journal of experimental medicine.

[34]  C. Nathan,et al.  Extracellular cytolysis by activated macrophages and granulocytes. II. Hydrogen peroxide as a mediator of cytotoxicity , 1979, The Journal of experimental medicine.

[35]  I. Fridovich.  The biology of oxygen radicals. , 1978, Science.

[36]  H. Rasmussen,et al.  Regulation of pyruvate carboxylase activity by calcium in intact rat liver mitochondria. , 1969, The Journal of biological chemistry.

[37]  J R Subjeck,et al.  Stress protein systems of mammalian cells. , 1986, The American journal of physiology.

[38]  H. Pelham,et al.  What turns on heat shock genes? , 1985, Nature.

[39]  J. Cheung,et al.  Determination of isolated myocyte viability: staining methods and functional criteria. , 1985, Basic research in cardiology.

[40]  T. Slater.  Free-radical mechanisms in tissue injury. , 1984, The Biochemical journal.

[41]  D. Bikle.  The vitamin D endocrine system. , 1982, Advances in internal medicine.

[42]  Michael Ashburner,et al.  Heat shock, from bacteria to man , 1982 .