Resveratrol protects against 4‐HNE induced oxidative stress and apoptosis in Swiss 3T3 fibroblasts

Here we report on the marked protective effect of resveratrol on 4‐hydroxynonenal (4‐HNE) induced oxidative stress and apoptotic death in Swiss 3T3 fibroblasts. 4‐HNE, one of the major aldehydic products of the peroxidation of membrane w‐6 polyunsaturated fatty acids, has been suggested to contribute to oxidant stress mediated cell injury. Indeed, in vitro treatment of 3T3 fibroblasts with 4‐HNE induced a condition of oxidative stress as monitored by the oxidation of dichlorofluorescein diacetate; this reaction was prevented when cells were pretreated with resveratrol. Further, 4‐HNE‐treated fibroblasts eventually underwent apoptotic death as determined by differential staining and internucleosomal DNA fragmentation. Resveratrol pretreatment also prevented 4‐HNE induced DNA fragmentation and apoptosis. These observations are consistent with a potential role of lipid peroxidation‐derived products in programmed cell death and demonstrate that resveratrol can counteract this effect by quenching cell oxidative stress.

[1]  B. Halliwell,et al.  Proteasomal dysfunction induced by 4‐hydroxy‐2,3‐trans‐nonenal, an end‐product of lipid peroxidation: a mechanism contributing to neurodegeneration? , 2002, Journal of neurochemistry.

[2]  U. Kompella,et al.  Induction of vascular endothelial growth factor by 4-hydroxynonenal and its prevention by glutathione precursors in retinal pigment epithelial cells. , 2002, European journal of pharmacology.

[3]  J. Pezzuto,et al.  Cancer Chemopreventive Activity of Resveratrol , 2002, Drugs under experimental and clinical research.

[4]  T. Dinis,et al.  The Interaction of Resveratrol with Ferrylmyoglobin and Peroxynitrite; Protection Against LDL Oxidation , 2002, Free radical research.

[5]  C. Stancu,et al.  Modified lipoproteins accumulate in human coronary atheroma , 2002, Journal of cellular and molecular medicine.

[6]  J. Abe,et al.  Endothelial Atheroprotective and Anti‐inflammatory Mechanisms , 2001, Annals of the New York Academy of Sciences.

[7]  D. Graham,et al.  4‐Hydroxynonenal Immunoreactivity is Increased in Human Hippocampus After Global Ischemia , 2001, Brain pathology.

[8]  G. Poli,et al.  Physiological amounts of ascorbate potentiate phorbol ester-induced nuclear-binding of AP-1 transcription factor in cells of macrophagic lineage. , 2001, Free radical biology & medicine.

[9]  L. Marnett,et al.  4-hydroxynonenal induces apoptosis via caspase-3 activation and cytochrome c release. , 2001, Chemical research in toxicology.

[10]  R. Haynes,et al.  Apoptosis in RAW 264.7 cells exposed to 4-hydroxy-2-nonenal: dependence on cytochrome C release but not p53 accumulation. , 2001, Free radical biology & medicine.

[11]  M. Meydani.  Nutrition Interventions in Aging and Age‐Associated Disease , 2001, Annals of the New York Academy of Sciences.

[12]  C. Bode,et al.  4-Hydroxynonenal induces apoptosis, NF-κB-activation and formation of 8-isoprostane in vascular smooth nmuscle cells , 2001, Basic Research in Cardiology.

[13]  A. Davalli,et al.  Fluorescent dyes for cell viability: an application on prefixed conditions , 2001, Histochemistry and Cell Biology.

[14]  M. Mattson,et al.  The lipid peroxidation product 4-hydroxy-2,3-nonenal inhibits constitutive and inducible activity of nuclear factor kappa B in neurons. , 2000, Brain research. Molecular brain research.

[15]  K. Irani.  Oxidant signaling in vascular cell growth, death, and survival : a review of the roles of reactive oxygen species in smooth muscle and endothelial cell mitogenic and apoptotic signaling. , 2000, Circulation research.

[16]  P. Brundin,et al.  trans‐Resveratrol Protects Embryonic Mesencephalic Cells from tert‐Butyl Hydroperoxide , 2000, Journal of neurochemistry.

[17]  J. J. Moreno,et al.  Effect of resveratrol, a natural polyphenolic compound, on reactive oxygen species and prostaglandin production. , 2000, Biochemical pharmacology.

[18]  W. Markesbery,et al.  4‐hydroxynonenal increases neuronal susceptibility to oxidative stress , 1999, Journal of neuroscience research.

[19]  M. Maccarrone,et al.  Resveratrol prevents apoptosis in K562 cells by inhibiting lipoxygenase and cyclooxygenase activity. , 1999, European journal of biochemistry.

[20]  Y. Surh,et al.  Molecular mechanisms of chemopreventive effects of selected dietary and medicinal phenolic substances. , 1999, Mutation research.

[21]  P. Eckl,et al.  Cytotoxic and genotoxic effects of 4-hydroxynonenal in cerebral endothelial cells. , 1997, Mutation research.

[22]  H. Schröder,et al.  Aspirin protects endothelial cells from oxidative stress – possible synergism with vitamin E , 1997, FEBS letters.

[23]  M. Mattson,et al.  4‐Hydroxynonenal, an Aldehydic Product of Lipid Peroxidation, Impairs Signal Transduction Associated with Muscarinic Acetylcholine and Metabotropic Glutamate Receptors: Possible Action on Gαq/11 , 1997, Journal of neurochemistry.

[24]  M. Mattson,et al.  Impairment of Glucose and Glutamate Transport and Induction of Mitochondrial Oxidative Stress and Dysfunction in Synaptosomes by Amyloid β‐Peptide: Role of the Lipid Peroxidation Product 4‐Hydroxynonenal , 1997, Journal of neurochemistry.

[25]  D M Goldberg,et al.  Resveratrol: a molecule whose time has come? And gone? , 1997, Clinical biochemistry.

[26]  R J Mark,et al.  Amyloid β-Peptide Impairs Glucose Transport in Hippocampal and Cortical Neurons: Involvement of Membrane Lipid Peroxidation , 1997, The Journal of Neuroscience.

[27]  Norman R. Farnsworth,et al.  Cancer Chemopreventive Activity of Resveratrol, a Natural Product Derived from Grapes , 1997, Science.

[28]  M. Jacobson.  Reactive oxygen species and programmed cell death. , 1996, Trends in biochemical sciences.

[29]  D. Collen,et al.  Malondialdehyde-modified low density lipoproteins in patients with atherosclerotic disease. , 1995, The Journal of clinical investigation.

[30]  D. Collen,et al.  Malondialdehyde-modified low density lipoproteins in patients with atherosclerotic disease , 1995 .

[31]  R. Youle,et al.  Apoptosis and Free Radicals , 1994, Annals of the New York Academy of Sciences.

[32]  R. Schaur,et al.  The lipid peroxidation product 4-hydroxynonenal is formed by--and is able to attract--rat neutrophils in vivo. , 1994, Free radical research.

[33]  H. Esterbauer,et al.  Cytotoxicity and genotoxicity of lipid-oxidation products. , 1993, The American journal of clinical nutrition.

[34]  B. Halliwell,et al.  Free radicals in biology and medicine , 1985 .

[35]  D. Harrison.  Oxidant Signaling in Vascular Cell Growth , Death , and Survival A Review of the Roles of Reactive Oxygen Species in Smooth Muscle and Endothelial Cell Mitogenic and Apoptotic Signaling , 2000 .

[36]  E. Diamandis,et al.  Wine as a biological fluid: History, production, and role in disease prevention , 1997, Journal of clinical laboratory analysis.

[37]  H. Esterbauer,et al.  Chemistry and biochemistry of 4-hydroxynonenal, malonaldehyde and related aldehydes. , 1991, Free radical biology & medicine.

[38]  T. Slater,et al.  Free radicals, lipid peroxidation and cancer , 1982 .