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Erschienen in: Diabetologia 7/2007

01.07.2007 | Article

Reactive oxygen species mediate a cellular ‘memory’ of high glucose stress signalling

verfasst von: M. A. Ihnat, J. E. Thorpe, C. D. Kamat, C. Szabó, D. E. Green, L. A. Warnke, Z. Lacza, A. Cselenyák, K. Ross, S. Shakir, L. Piconi, R. C. Kaltreider, A. Ceriello

Erschienen in: Diabetologia | Ausgabe 7/2007

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Abstract

Aims/hypothesis

A long-term ‘memory’ of hyperglycaemic stress, even when glycaemia is normalised, has been previously reported in endothelial cells. In this report we sought to duplicate and extend this finding.

Materials and methods

HUVECs and ARPE-19 retinal cells were incubated in 5 or in 30 mmol/l glucose for 3 weeks or subjected to 1 week of normal glucose after being exposed for 2 weeks to continuous high glucose. HUVECs were also treated in this last condition with several antioxidants. Similarly, four groups of rats were studied for 3 weeks: (1) normal rats; (2) diabetic rats not treated with insulin; (3) diabetic rats treated with insulin during the last week; and (4) diabetic rats treated with insulin plus α-lipoic acid in the last week.

Results

In human endothelial cells and ARPE-19 retinal cells in culture, as well as in the retina of diabetic rats, levels of the following markers of high glucose stress remained induced for 1 week after levels of glucose had normalised: protein kinase C-β, NAD(P)H oxidase subunit p47phox, BCL-2-associated X protein, 3-nitrotyrosine, fibronectin, poly(ADP-ribose) Blockade of reactive species using different approaches, i.e. the mitochondrial antioxidant α-lipoic acid, overexpression of uncoupling protein 2, oxypurinol, apocynin and the poly(ADP-ribose) polymerase inhibitor PJ34, interrupted the induction both of high glucose stress markers and of the fluorescent reactive oxygen species (ROS) probe CM-H2DCFDA in human endothelial cells. Similar results were obtained in the retina of diabetic rats with α-lipoic acid added to the last week of normalised glucose.

Conclusions/interpretation

These results provide proof-of-principle of a ROS-mediated cellular persistence of vascular stress after glucose normalisation.
Literatur
1.
Zurück zum Zitat Laakso M (1999) Hyperglycaemia as a risk factor for cardiovascular disease in type 2 diabetes. Prim Care 26:829–839PubMed Laakso M (1999) Hyperglycaemia as a risk factor for cardiovascular disease in type 2 diabetes. Prim Care 26:829–839PubMed
2.
Zurück zum Zitat Dandona P, Chaudhuri A, Aljada A (2004) Endothelial dysfunction and hypertension in diabetes mellitus. Med Clin North Am 88:911–931, x–xiCrossRefPubMed Dandona P, Chaudhuri A, Aljada A (2004) Endothelial dysfunction and hypertension in diabetes mellitus. Med Clin North Am 88:911–931, x–xiCrossRefPubMed
3.
Zurück zum Zitat Soriano FG, Virag L, Szabo C (2001) Diabetic endothelial dysfunction: role of reactive oxygen and nitrogen species production and poly(ADP-ribose) polymerase activation. J Mol Med 79:437–448CrossRefPubMed Soriano FG, Virag L, Szabo C (2001) Diabetic endothelial dysfunction: role of reactive oxygen and nitrogen species production and poly(ADP-ribose) polymerase activation. J Mol Med 79:437–448CrossRefPubMed
4.
Zurück zum Zitat Nishikawa T, Edelstein D, Du XL et al (2000) Normalizing mitochondrial superoxide production blocks three pathways of hyperglycaemic damage. Nature 404:787–790CrossRefPubMed Nishikawa T, Edelstein D, Du XL et al (2000) Normalizing mitochondrial superoxide production blocks three pathways of hyperglycaemic damage. Nature 404:787–790CrossRefPubMed
5.
Zurück zum Zitat Cai H, Harrison DG (2000) Endothelial dysfunction in cardiovascular diseases: the role of oxidant stress. Circ Res 87:840–844PubMed Cai H, Harrison DG (2000) Endothelial dysfunction in cardiovascular diseases: the role of oxidant stress. Circ Res 87:840–844PubMed
6.
Zurück zum Zitat Lee TS, MacGregor LC, Fluharty SJ, King GL (1989) Differential regulation of protein kinase C and (Na,K)-adenosine triphosphatase activities by elevated glucose levels in retinal capillary endothelial cells. J Clin Invest 83:90–94PubMedCrossRef Lee TS, MacGregor LC, Fluharty SJ, King GL (1989) Differential regulation of protein kinase C and (Na,K)-adenosine triphosphatase activities by elevated glucose levels in retinal capillary endothelial cells. J Clin Invest 83:90–94PubMedCrossRef
7.
Zurück zum Zitat Garcia Soriano F, Virág L, Jagtap P et al (2001) Diabetic endothelial dysfunction: the role of poly(ADP-ribose) polymerase activation. Nat Med 7:108–113CrossRefPubMed Garcia Soriano F, Virág L, Jagtap P et al (2001) Diabetic endothelial dysfunction: the role of poly(ADP-ribose) polymerase activation. Nat Med 7:108–113CrossRefPubMed
8.
Zurück zum Zitat Kimmelstiel P, Osawa G, Beres J (1966) Glomerular basement membrane in diabetics. Am J Clin Pathol 45:21–31PubMed Kimmelstiel P, Osawa G, Beres J (1966) Glomerular basement membrane in diabetics. Am J Clin Pathol 45:21–31PubMed
9.
Zurück zum Zitat Kern TS, Tang J, Mizutani M et al (2000) Response of capillary cell death to aminoguanidine predicts the development of retinopathy: comparison of diabetes and galactosemia. Invest Ophthalmol Vis Sci 41:3972–3978PubMed Kern TS, Tang J, Mizutani M et al (2000) Response of capillary cell death to aminoguanidine predicts the development of retinopathy: comparison of diabetes and galactosemia. Invest Ophthalmol Vis Sci 41:3972–3978PubMed
10.
Zurück zum Zitat Cagliero E, Maiello M, Boeri D, Roy S, Lorenzi M (1988) Increased expression of basement membrane components in human endothelial cells cultured in high glucose. J Clin Invest 82:735–738PubMed Cagliero E, Maiello M, Boeri D, Roy S, Lorenzi M (1988) Increased expression of basement membrane components in human endothelial cells cultured in high glucose. J Clin Invest 82:735–738PubMed
11.
Zurück zum Zitat Roy S, Sala R, Cagliero E, Lorenzi M (1990) Overexpression of fibronectin induced by diabetes or high glucose: phenomenon with a memory. Proc Natl Acad Sci USA 87:404–408CrossRefPubMed Roy S, Sala R, Cagliero E, Lorenzi M (1990) Overexpression of fibronectin induced by diabetes or high glucose: phenomenon with a memory. Proc Natl Acad Sci USA 87:404–408CrossRefPubMed
12.
Zurück zum Zitat Engerman RL, Kern TS (1987) Progression of incipient diabetic retinopathy during good glycaemic control. Diabetes 36:808–812CrossRefPubMed Engerman RL, Kern TS (1987) Progression of incipient diabetic retinopathy during good glycaemic control. Diabetes 36:808–812CrossRefPubMed
13.
Zurück zum Zitat Savitha S, Tamilselvan J, Anusuyadevi M, Panneerselvam C (2005) Oxidative stress on mitochondrial antioxidant defense system in the aging process: role of dl-alpha-lipoic acid and L-carnitine. Clin Chim Acta 355:173–180CrossRefPubMed Savitha S, Tamilselvan J, Anusuyadevi M, Panneerselvam C (2005) Oxidative stress on mitochondrial antioxidant defense system in the aging process: role of dl-alpha-lipoic acid and L-carnitine. Clin Chim Acta 355:173–180CrossRefPubMed
14.
Zurück zum Zitat Barchowsky A, Klei LR, Dudek EJ, Swartz HM, James PE (1999) Stimulation of reactive oxygen, but not reactive nitrogen species, in vascular endothelial cells exposed to low levels of arsenite. Free Radic Biol Med 27:1405–1412CrossRefPubMed Barchowsky A, Klei LR, Dudek EJ, Swartz HM, James PE (1999) Stimulation of reactive oxygen, but not reactive nitrogen species, in vascular endothelial cells exposed to low levels of arsenite. Free Radic Biol Med 27:1405–1412CrossRefPubMed
15.
Zurück zum Zitat Ichikawa H, Wolf RE, Aw TY et al (1997) Exogenous xanthine promotes neutrophil adherence to cultured endothelial cells. Am J Physiol 273:G342–G347PubMed Ichikawa H, Wolf RE, Aw TY et al (1997) Exogenous xanthine promotes neutrophil adherence to cultured endothelial cells. Am J Physiol 273:G342–G347PubMed
16.
Zurück zum Zitat Piconi L, Quagliaro L, Da Ros R et al (2004) Intermittent high glucose enhances ICAM-1, VCAM-1, E-selectin and interleukin-6 expression in human umbilical endothelial cells in culture: the role of poly(ADP-ribose) polymerase. J Thromb Haemost 2:1453–1459CrossRefPubMed Piconi L, Quagliaro L, Da Ros R et al (2004) Intermittent high glucose enhances ICAM-1, VCAM-1, E-selectin and interleukin-6 expression in human umbilical endothelial cells in culture: the role of poly(ADP-ribose) polymerase. J Thromb Haemost 2:1453–1459CrossRefPubMed
17.
Zurück zum Zitat Zou MH, Kirkpatrick SS, Davis BJ et al (2004) Activation of the AMP-activated protein kinase by the anti-diabetic drug metformin in vivo. Role of mitochondrial reactive nitrogen species. J Biol Chem 279:43940–43951CrossRefPubMed Zou MH, Kirkpatrick SS, Davis BJ et al (2004) Activation of the AMP-activated protein kinase by the anti-diabetic drug metformin in vivo. Role of mitochondrial reactive nitrogen species. J Biol Chem 279:43940–43951CrossRefPubMed
18.
Zurück zum Zitat Zhang SX, Sima J, Shao C et al (2004) Plasminogen kringle 5 reduces vascular leakage in the retina in rat models of oxygen-induced retinopathy and diabetes. Diabetologia 47:124–131CrossRefPubMed Zhang SX, Sima J, Shao C et al (2004) Plasminogen kringle 5 reduces vascular leakage in the retina in rat models of oxygen-induced retinopathy and diabetes. Diabetologia 47:124–131CrossRefPubMed
19.
Zurück zum Zitat Tomita S, Li RK, Weisel RD et al (1999) Autologous transplantation of bone marrow cells improves damaged heart function. Circulation 100:II247–II256PubMed Tomita S, Li RK, Weisel RD et al (1999) Autologous transplantation of bone marrow cells improves damaged heart function. Circulation 100:II247–II256PubMed
20.
Zurück zum Zitat Kowluru RA, Odenbach S (2004) Effect of long-term administration of alpha-lipoic acid on retinal capillary cell death and the development of retinopathy in diabetic rats. Diabetes 53:3233–3238CrossRefPubMed Kowluru RA, Odenbach S (2004) Effect of long-term administration of alpha-lipoic acid on retinal capillary cell death and the development of retinopathy in diabetic rats. Diabetes 53:3233–3238CrossRefPubMed
21.
Zurück zum Zitat Navratil E, Couvelard A, Rey A, Hénin D, Scoazec JY (1997) Expression of cell adhesion molecules by microvascular endothelial cells in the cortical and subcortical regions of the normal human brain: an immunohistochemical analysis. Neuropathol Appl Neurobiol 23:68–80CrossRefPubMed Navratil E, Couvelard A, Rey A, Hénin D, Scoazec JY (1997) Expression of cell adhesion molecules by microvascular endothelial cells in the cortical and subcortical regions of the normal human brain: an immunohistochemical analysis. Neuropathol Appl Neurobiol 23:68–80CrossRefPubMed
22.
Zurück zum Zitat Mishra DP, Pal R, Shaha C (2006) Changes in cytosolic Ca2+ levels regulate Bcl-xS and Bcl-xL expression in spermatogenic cells during apoptotic death. J Biol Chem 281:2133–2143CrossRefPubMed Mishra DP, Pal R, Shaha C (2006) Changes in cytosolic Ca2+ levels regulate Bcl-xS and Bcl-xL expression in spermatogenic cells during apoptotic death. J Biol Chem 281:2133–2143CrossRefPubMed
23.
Zurück zum Zitat Dixon AJ, Burns J, Dunnill MS, McGee JO (1980) Distribution of fibronectin in normal and diseased human kidneys. J Clin Pathol 33:1021–1028CrossRefPubMed Dixon AJ, Burns J, Dunnill MS, McGee JO (1980) Distribution of fibronectin in normal and diseased human kidneys. J Clin Pathol 33:1021–1028CrossRefPubMed
24.
Zurück zum Zitat Abebe W, MacLeod KM (1990) Protein kinase C-mediated contractile responses of arteries from diabetic rats. Br J Pharmacol 101:465–471PubMed Abebe W, MacLeod KM (1990) Protein kinase C-mediated contractile responses of arteries from diabetic rats. Br J Pharmacol 101:465–471PubMed
25.
Zurück zum Zitat Lee TS, Saltsman KA, Ohashi H, King GL (1989) Activation of protein kinase C by elevation of glucose concentration: proposal for a mechanism in the development of diabetic vascular complications. Proc Natl Acad Sci USA 86:5141–5145CrossRefPubMed Lee TS, Saltsman KA, Ohashi H, King GL (1989) Activation of protein kinase C by elevation of glucose concentration: proposal for a mechanism in the development of diabetic vascular complications. Proc Natl Acad Sci USA 86:5141–5145CrossRefPubMed
26.
Zurück zum Zitat Korsmeyer SJ, Shutter JR, Veis DJ, Merry DE, Oltvai ZN (1993) Bcl-2/Bax: a rheostat that regulates an anti-oxidant pathway and cell death. Semin Cancer Biol 4:327–332PubMed Korsmeyer SJ, Shutter JR, Veis DJ, Merry DE, Oltvai ZN (1993) Bcl-2/Bax: a rheostat that regulates an anti-oxidant pathway and cell death. Semin Cancer Biol 4:327–332PubMed
27.
Zurück zum Zitat Podestà F, Romeo G, Liu WH et al (2000) Bax is increased in the retina of diabetic subjects and is associated with pericyte apoptosis in vivo and in vitro. Am J Pathol 156:1025–1032PubMed Podestà F, Romeo G, Liu WH et al (2000) Bax is increased in the retina of diabetic subjects and is associated with pericyte apoptosis in vivo and in vitro. Am J Pathol 156:1025–1032PubMed
28.
Zurück zum Zitat Guzik TJ, Mussa S, Gastaldi D et al (2002) Mechanisms of increased vascular superoxide production in human diabetes mellitus: role of NAD(P)H oxidase and endothelial nitric oxide synthase. Circulation 105:1656–1662CrossRefPubMed Guzik TJ, Mussa S, Gastaldi D et al (2002) Mechanisms of increased vascular superoxide production in human diabetes mellitus: role of NAD(P)H oxidase and endothelial nitric oxide synthase. Circulation 105:1656–1662CrossRefPubMed
29.
Zurück zum Zitat Ceriello A, Quagliaro L, Catone B et al (2002) Role of hyperglycaemia in nitrotyrosine postprandial generation. Diabetes Care 25:1439–1443CrossRefPubMed Ceriello A, Quagliaro L, Catone B et al (2002) Role of hyperglycaemia in nitrotyrosine postprandial generation. Diabetes Care 25:1439–1443CrossRefPubMed
30.
Zurück zum Zitat Ceriello A, Quagliaro L, D’Amico M et al (2002) Acute hyperglycaemia induces nitrotyrosine formation and apoptosis in perfused heart from rat. Diabetes 51:1076–1082CrossRefPubMed Ceriello A, Quagliaro L, D’Amico M et al (2002) Acute hyperglycaemia induces nitrotyrosine formation and apoptosis in perfused heart from rat. Diabetes 51:1076–1082CrossRefPubMed
31.
Zurück zum Zitat Ceriello A, Taboga C, Tonutti L et al (2002) Evidence for an independent and cumulative effect of postprandial hypertriglyceridemia and hyperglycemia on endothelial dysfunction and oxidative stress generation: effects of short- and long-term simvastatin treatment. Circulation 106:1211–1218CrossRefPubMed Ceriello A, Taboga C, Tonutti L et al (2002) Evidence for an independent and cumulative effect of postprandial hypertriglyceridemia and hyperglycemia on endothelial dysfunction and oxidative stress generation: effects of short- and long-term simvastatin treatment. Circulation 106:1211–1218CrossRefPubMed
32.
Zurück zum Zitat Ceriello A, Mercuri F, Quagliaro L et al (2001) Detection of nitrotyrosine in the diabetic plasma: evidence of oxidative stress. Diabetologia 44:834–838CrossRefPubMed Ceriello A, Mercuri F, Quagliaro L et al (2001) Detection of nitrotyrosine in the diabetic plasma: evidence of oxidative stress. Diabetologia 44:834–838CrossRefPubMed
33.
Zurück zum Zitat Quagliaro L, Piconi L, Assaloni R, Martinelli L, Motz E, Ceriello A (2003) Intermittent high glucose enhances apoptosis related to oxidative stress in human umbilical vein endothelial cells: the role of protein kinase C and NAD(P)H-oxidase activation. Diabetes 52:2795–2804CrossRefPubMed Quagliaro L, Piconi L, Assaloni R, Martinelli L, Motz E, Ceriello A (2003) Intermittent high glucose enhances apoptosis related to oxidative stress in human umbilical vein endothelial cells: the role of protein kinase C and NAD(P)H-oxidase activation. Diabetes 52:2795–2804CrossRefPubMed
34.
Zurück zum Zitat Thies RL, Autor AP (1991) Reactive oxygen injury to cultured pulmonary artery endothelial cells: mediation by poly(ADP-ribose) polymerase activation causing NAD depletion and altered energy balance. Arch Biochem Biophys 286:353–363CrossRefPubMed Thies RL, Autor AP (1991) Reactive oxygen injury to cultured pulmonary artery endothelial cells: mediation by poly(ADP-ribose) polymerase activation causing NAD depletion and altered energy balance. Arch Biochem Biophys 286:353–363CrossRefPubMed
35.
Zurück zum Zitat Wu WS, Tsai RK, Chang CH, Wang S, Wu JR, Chang YX (2006) Reactive oxygen species mediated sustained activation of protein kinase C alpha and extracellular signal-regulated kinase for migration of human hepatoma cell Hepg2. Mol Cancer Res 4:747–758CrossRefPubMed Wu WS, Tsai RK, Chang CH, Wang S, Wu JR, Chang YX (2006) Reactive oxygen species mediated sustained activation of protein kinase C alpha and extracellular signal-regulated kinase for migration of human hepatoma cell Hepg2. Mol Cancer Res 4:747–758CrossRefPubMed
36.
Zurück zum Zitat Lin J, Bierhaus A, Bugert P et al (2006) Effect of R-(+)-alpha-lipoic acid on experimental diabetic retinopathy. Diabetologia 49:1089–1096CrossRefPubMed Lin J, Bierhaus A, Bugert P et al (2006) Effect of R-(+)-alpha-lipoic acid on experimental diabetic retinopathy. Diabetologia 49:1089–1096CrossRefPubMed
37.
Zurück zum Zitat Sakamoto K, Yamasaki Y, Kaneto H et al (1999) Identification of oxidative stress-regulated genes in rat aortic smooth muscle cells by suppression subtractive hybridization. FEBS Lett 461:47–51CrossRefPubMed Sakamoto K, Yamasaki Y, Kaneto H et al (1999) Identification of oxidative stress-regulated genes in rat aortic smooth muscle cells by suppression subtractive hybridization. FEBS Lett 461:47–51CrossRefPubMed
38.
Zurück zum Zitat Siwik DA, Pagano PJ, Colucci WS (2001) Oxidative stress regulates collagen synthesis and matrix metalloproteinase activity in cardiac fibroblasts. Am J Physiol Cell Physiol 280:C53–C60PubMed Siwik DA, Pagano PJ, Colucci WS (2001) Oxidative stress regulates collagen synthesis and matrix metalloproteinase activity in cardiac fibroblasts. Am J Physiol Cell Physiol 280:C53–C60PubMed
39.
Zurück zum Zitat Korchak HM, Rossi MW, Kilpatrick LE (1998) Selective role for beta-protein kinase C in signaling for \({\text{O}}^{{\text{ - }}}_{{\text{2}}} \) generation but not degranulation or adherence in differentiated HL60 cells. J Biol Chem 273:27292–27299CrossRefPubMed Korchak HM, Rossi MW, Kilpatrick LE (1998) Selective role for beta-protein kinase C in signaling for \({\text{O}}^{{\text{ - }}}_{{\text{2}}} \) generation but not degranulation or adherence in differentiated HL60 cells. J Biol Chem 273:27292–27299CrossRefPubMed
40.
Zurück zum Zitat Sellak H, Franzini E, Hakim J, Pasquier C (1994) Reactive oxygen species rapidly increase endothelial ICAM-1 ability to bind neutrophils without detectable upregulation. Blood 83:2669–2677PubMed Sellak H, Franzini E, Hakim J, Pasquier C (1994) Reactive oxygen species rapidly increase endothelial ICAM-1 ability to bind neutrophils without detectable upregulation. Blood 83:2669–2677PubMed
41.
Zurück zum Zitat Korsmeyer SJ, Yin XM, Oltvai ZN, Veis-Novack DJ, Linette GP (1995) Reactive oxygen species and the regulation of cell death by the Bcl-2 gene family. Biochim Biophys Acta 1271:63–66PubMed Korsmeyer SJ, Yin XM, Oltvai ZN, Veis-Novack DJ, Linette GP (1995) Reactive oxygen species and the regulation of cell death by the Bcl-2 gene family. Biochim Biophys Acta 1271:63–66PubMed
42.
Zurück zum Zitat Venugopal SK, Devaraj S, Yang T, Jialal I (2002) Alpha-tocopherol decreases superoxide anion release in human monocytes under hyperglycaemic conditions via inhibition of protein kinase C-alpha. Diabetes 51:3049–3054CrossRefPubMed Venugopal SK, Devaraj S, Yang T, Jialal I (2002) Alpha-tocopherol decreases superoxide anion release in human monocytes under hyperglycaemic conditions via inhibition of protein kinase C-alpha. Diabetes 51:3049–3054CrossRefPubMed
43.
Zurück zum Zitat Rosca MG, Monnier VM, Szweda LI, Weiss MF (2002) Alterations in renal mitochondrial respiration in response to the reactive oxoaldehyde methylglyoxal. Am J Physiol Renal Physiol 283:F52–F59PubMed Rosca MG, Monnier VM, Szweda LI, Weiss MF (2002) Alterations in renal mitochondrial respiration in response to the reactive oxoaldehyde methylglyoxal. Am J Physiol Renal Physiol 283:F52–F59PubMed
44.
Zurück zum Zitat Rosca MG, Mustata TG, Kinter MT et al (2005) Glycation of mitochondrial proteins from diabetic rat kidney is associated with excess superoxide formation. Am J Physiol Renal Physiol 289:F420–F430CrossRefPubMed Rosca MG, Mustata TG, Kinter MT et al (2005) Glycation of mitochondrial proteins from diabetic rat kidney is associated with excess superoxide formation. Am J Physiol Renal Physiol 289:F420–F430CrossRefPubMed
45.
Zurück zum Zitat Goldin A, Beckman JA, Schmidt AM, Creager MA (2006) Advanced glycation end products: sparking the development of diabetic vascular injury. Circulation 114:597–605CrossRefPubMed Goldin A, Beckman JA, Schmidt AM, Creager MA (2006) Advanced glycation end products: sparking the development of diabetic vascular injury. Circulation 114:597–605CrossRefPubMed
46.
Zurück zum Zitat Stuart JA, Brown MF (2006) Mitochondrial DNA maintenance and bioenergetics. Biochim Biophys Acta 1757:79–89CrossRefPubMed Stuart JA, Brown MF (2006) Mitochondrial DNA maintenance and bioenergetics. Biochim Biophys Acta 1757:79–89CrossRefPubMed
47.
Zurück zum Zitat Kang D, Hamasaki N (2003) Mitochondrial oxidative stress and mitochondrial DNA. Clin Chem Lab Med 41:1281–1288CrossRefPubMed Kang D, Hamasaki N (2003) Mitochondrial oxidative stress and mitochondrial DNA. Clin Chem Lab Med 41:1281–1288CrossRefPubMed
48.
Zurück zum Zitat Gutierrez J, Ballinger SW, Darley-Usmar VM, Landar A (2006) Free radicals, mitochondria, and oxidized lipids: the emerging role in signal transduction in vascular cells. Circ Res 99:924–932CrossRefPubMed Gutierrez J, Ballinger SW, Darley-Usmar VM, Landar A (2006) Free radicals, mitochondria, and oxidized lipids: the emerging role in signal transduction in vascular cells. Circ Res 99:924–932CrossRefPubMed
49.
Zurück zum Zitat Brownlee M (2001) Biochemistry and molecular cell biology of diabetic complications. Nature 414:813–820CrossRefPubMed Brownlee M (2001) Biochemistry and molecular cell biology of diabetic complications. Nature 414:813–820CrossRefPubMed
Metadaten
Titel
Reactive oxygen species mediate a cellular ‘memory’ of high glucose stress signalling
verfasst von
M. A. Ihnat
J. E. Thorpe
C. D. Kamat
C. Szabó
D. E. Green
L. A. Warnke
Z. Lacza
A. Cselenyák
K. Ross
S. Shakir
L. Piconi
R. C. Kaltreider
A. Ceriello
Publikationsdatum
01.07.2007
Verlag
Springer-Verlag
Erschienen in
Diabetologia / Ausgabe 7/2007
Print ISSN: 0012-186X
Elektronische ISSN: 1432-0428
DOI
https://doi.org/10.1007/s00125-007-0684-2

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