Genistein and Folic Acid Prevent Oxidative Injury Induced by β‐Amyloid Peptide

Abstract:  To explore the mechanism(s) of the neuroprotective effects of genistein (GEN) and folic acid (FA) on neurons treated with beta amyloid 31–35 (Aβ31–35), the primary cultured cortical neurons were treated with GEN and/or FA for 2 hr prior to exposure to Aβ31–35. Cell viability and fluidity of cell membrane were measured by 3‐[4,5‐dimethylthiazol‐2]‐2,5 diphenyltetrazolium bromide and fluorescence polarization, respectively. Intracellular reactive oxygen species (ROS) and Ca2+ concentrations were measured by laser scanning confocal microscope. Glutataione (GSH) and Glutathione disulfide (GSSG) in mitochondria were measured by enzymatic method. Flow cytometry technique was used to measure mitochondrial membrane potential. The expression of HCY‐2 and p38‐MAPK mRNA in neurons was analysed by reverse transcription‐polymerase chain reaction (RT‐PCR). The results showed that GEN and/or FA increased cell viability and reduced concentration of Ca2+ and generation of ROS in neurons compared with Aβ31–35‐treated cells. Furthermore, the ratio of GSH/GSSG in mitochondria and mitochondrial membrane potential was increased after GEN and/or FA treatment. RT‐PCR results showed that GEN and/or FA down‐regulated expression of HCY‐2 and p38‐MAPK mRNA. We conclude that GEN and/or FA had neuroprotective effects in Aβ31–35‐treated neurons. The mechanisms might be associated with multiple factors such as maintaining redox balance, stabilizing mitochondrial membrane integrity and modulating the signal pathways related to oxidation and apoptosis.

[1]  J. Geurts,et al.  Mitochondrial dysfunction: a potential link between neuroinflammation and neurodegeneration? , 2010, Mitochondrion (Amsterdam. Print).

[2]  R. Xiao,et al.  Genistein as a neuroprotective antioxidant attenuates redox imbalance induced by β-amyloid peptides 25–35 in PC12 cells , 2010, International Journal of Developmental Neuroscience.

[3]  Y. Ishimi,et al.  Effect of soy isoflavone extract supplements on bone mineral density in menopausal women: meta-analysis of randomized controlled trials. , 2010, Asia Pacific journal of clinical nutrition.

[4]  Haifeng Zhao,et al.  Folic acid and soybean isoflavone combined supplementation protects the post-neural tube closure defects of rodents induced by cyclophosphamide in vivo and in vitro. , 2010, Neurotoxicology.

[5]  N. Inestrosa,et al.  Amyloid-β-Acetylcholinesterase complexes potentiate neurodegenerative changes induced by the Aβ peptide. Implications for the pathogenesis of Alzheimer's disease , 2010, Molecular Neurodegeneration.

[6]  C. Matté,et al.  Acute homocysteine administration impairs memory consolidation on inhibitory avoidance task and decreases hippocampal brain-derived neurotrophic factor immunocontent: prevention by folic acid treatment , 2009, Neuroscience.

[7]  J. Buckley,et al.  Soya isoflavone supplementation enhances spatial working memory in men. , 2009, The British journal of nutrition.

[8]  Jie Zhang,et al.  Neuroprotective effects of genistein and folic acid on apoptosis of rat cultured cortical neurons induced by β-amyloid 31-35 , 2009, British Journal of Nutrition.

[9]  J. Tanus-Santos,et al.  Isoflavone genistein inhibits the angiotensin-converting enzyme and alters the vascular responses to angiotensin I and bradykinin. , 2009, European journal of pharmacology.

[10]  Huan-ling Yu,et al.  Neuroprotection of soyabean isoflavone co-administration with folic acid against β-amyloid 1-40-induced neurotoxicity in rats , 2009, British Journal of Nutrition.

[11]  C. Matté,et al.  Chronic hyperhomocysteinemia alters antioxidant defenses and increases DNA damage in brain and blood of rats: Protective effect of folic acid , 2009, Neurochemistry International.

[12]  D. Praticò.  Oxidative stress hypothesis in Alzheimer's disease: a reappraisal. , 2008, Trends in pharmacological sciences.

[13]  H. Ichijo,et al.  Redox control of cell fate by MAP kinase: physiological roles of ASK1-MAP kinase pathway in stress signaling. , 2008, Biochimica et biophysica acta.

[14]  M. Imhof,et al.  Effects of soy isoflavones on 17beta-estradiol-induced proliferation of MCF-7 breast cancer cells. , 2008, Toxicology in vitro : an international journal published in association with BIBRA.

[15]  Q. Wang,et al.  Folic acid protects motor neurons against the increased homocysteine, inflammation and apoptosis in SOD1G93A transgenic mice , 2008, Neuropharmacology.

[16]  J. Sastre,et al.  Oestradiol or genistein rescues neurons from amyloid beta‐induced cell death by inhibiting activation of p38 , 2008, Aging cell.

[17]  R. Xiao,et al.  Developmental neurotoxicity role of cyclophosphamide on post-neural tube closure of rodents in vitro and in vivo , 2007, International Journal of Developmental Neuroscience.

[18]  W. Klein,et al.  Aβ Oligomers Induce Neuronal Oxidative Stress through an N-Methyl-D-aspartate Receptor-dependent Mechanism That Is Blocked by the Alzheimer Drug Memantine* , 2007, Journal of Biological Chemistry.

[19]  Mei-na Wu,et al.  Amyloid β‐protein fragment 31–35 suppresses long‐term potentiation in hippocampal CA1 region of rats in vivo , 2006 .

[20]  Q. Xia,et al.  The neuroprotection conferred by activating the mitochondrial ATP-sensitive K+ channel is mediated by inhibiting the mitochondrial permeability transition pore , 2006, Neuroscience Letters.

[21]  T. Mukherjee,et al.  Folic acid as a Fenton-modulator: possible physiological implication. , 2006, Medicinal chemistry (Shariqah (United Arab Emirates)).

[22]  Y. Siow,et al.  Folic acid inhibits homocysteine-induced superoxide anion production and nuclear factor kappa B activation in macrophages. , 2006, Canadian journal of physiology and pharmacology.

[23]  T. Shea,et al.  Folate, vitamin E, and acetyl-l-carnitine provide synergistic protection against oxidative stress resulting from exposure of human neuroblastoma cells to amyloid-beta , 2005, Brain Research.

[24]  M. Coletta,et al.  Aβ(31–35) and Aβ(25–35) fragments of amyloid beta‐protein induce cellular death through apoptotic signals: Role of the redox state of methionine‐35 , 2005, FEBS letters.

[25]  D. Green,et al.  The Pathophysiology of Mitochondrial Cell Death , 2004, Science.

[26]  R. Aitken,et al.  The development of signal transduction pathways during epididymal maturation is calcium dependent. , 2004, Developmental biology.

[27]  Qi Chen,et al.  Genistein ameliorates beta-amyloid peptide (25-35)-induced hippocampal neuronal apoptosis. , 2004, Free radical biology & medicine.

[28]  J. Fernandez-Checa,et al.  Redox regulation and signaling lipids in mitochondrial apoptosis. , 2003, Biochemical and biophysical research communications.

[29]  D. Butterfield,et al.  Different mechanisms of oxidative stress and neurotoxicity for Alzheimer's A beta(1--42) and A beta(25--35). , 2001, Journal of the American Chemical Society.

[30]  J. Tang,et al.  [A novel apoptotic related gene--homocysteine-induced gene HCY-2]. , 2000, Zhongguo yi xue ke xue yuan xue bao. Acta Academiae Medicinae Sinicae.

[31]  M. Smith,et al.  Oxidative stress in Alzheimer's disease. , 2000, Biochimica et biophysica acta.

[32]  Á. Almeida,et al.  Nitric oxide mediates glutamate-induced mitochondrial depolarization in rat cortical neurons , 1999, Brain Research.

[33]  M. Ochsner.  Simultaneous measurement of Ca2+ transients and changes in the cell volume and microviscosity of the plasma membrane in smooth muscle cells. Evaluation of the effect of formoterol. , 1996, Biochemical pharmacology.

[34]  George Perry,et al.  Mitochondrial dysfunction is a trigger of Alzheimer's disease pathophysiology. , 2010, Biochimica et biophysica acta.

[35]  U. Das.  Folic acid and polyunsaturated fatty acids improve cognitive function and prevent depression, dementia, and Alzheimer's disease--but how and why? , 2008, Prostaglandins, leukotrienes, and essential fatty acids.

[36]  Liang Jiang,et al.  Study of the synergetic effect of folic acid and genistein on the early stage of primary cultured neuron apoptosis , 2004 .

[37]  Zhao Hai-fen.  The effect of genistein on the early-staged neuron apoptosis induced by cylophosphamide , 2004 .