Oxygen-glucose deprivation regulates BACE1 expression through induction of autophagy in Neuro-2a/APP695 cells

Our previous findings have demonstrated that autophagy regulation can alleviate the decline of learning and memory by eliminating deposition of extracellular beta-amyloid peptide (Aβ) in the brain after stroke, but the exact mechanism is unclear. It is presumed that the regulation of beta-site APP-cleaving enzyme 1 (BACE1), the rate-limiting enzyme in metabolism of Aβ, would be a key site. Neuro-2a/amyloid precursor protein 695 (APP695) cell models of cerebral ischemia were established by oxygen-glucose deprivation to investigate the effects of Rapamycin (an autophagy inducer) or 3-methyladenine (an autophagy inhibitor) on the expression of BACE1. Either oxygen-glucose deprivation or Rapamycin down-regulated the expression of BACE1 while 3-methyladenine up-regulated BACE1 expression. These results confirm that oxygen-glucose deprivation down-regulates BACE1 expression in Neuro-2a/APP695 cells through the introduction of autophagy.

[1]  Kshitiz,et al.  Chaperone-mediated Autophagy Targets Hypoxia-inducible Factor-1α (HIF-1α) for Lysosomal Degradation* , 2013, The Journal of Biological Chemistry.

[2]  R. Tanzi,et al.  SUMO1 modulates Aβ generation via BACE1 accumulation , 2013, Neurobiology of Aging.

[3]  A. Cavalli,et al.  Computational methods in the discovery and design of BACE-1 inhibitors. , 2012, Current medicinal chemistry.

[4]  S. Eketjäll,et al.  New aminoimidazoles as beta-secretase (BACE-1) inhibitors showing amyloid-beta (A beta ) lowering in brain. , 2012 .

[5]  S. Eketjäll,et al.  New aminoimidazoles as β-secretase (BACE-1) inhibitors showing amyloid-β (Aβ) lowering in brain. , 2012, Journal of medicinal chemistry.

[6]  M. Mintun,et al.  Amyloid deposition, hypometabolism, and longitudinal cognitive decline , 2012, Annals of neurology.

[7]  J. McLaurin,et al.  Inhibition of amyloid-beta peptide aggregation rescues the autophagic deficits in the TgCRND8 mouse model of Alzheimer disease. , 2012, Biochimica et biophysica acta.

[8]  S. Gandy,et al.  Dynamin 1 Regulates Amyloid Generation through Modulation of BACE-1 , 2012, PloS one.

[9]  S. Rivest,et al.  The early contribution of cerebrovascular factors to the pathogenesis of Alzheimer’s disease , 2012, The European journal of neuroscience.

[10]  K. Kawahara,et al.  Intracerebral microinjection of interleukin-4/interleukin-13 reduces β-amyloid accumulation in the ipsilateral side and improves cognitive deficits in young amyloid precursor protein 23 mice , 2012, Neuroscience.

[11]  J. Gronych,et al.  Hypoxia-induced autophagy promotes tumor cell survival and adaptation to antiangiogenic treatment in glioblastoma. , 2012, Cancer research.

[12]  M. Masserini,et al.  Aβ42 production in brain capillary endothelial cells after oxygen and glucose deprivation , 2012, Molecular and Cellular Neuroscience.

[13]  C. Rowe,et al.  Accelerated cortical atrophy in cognitively normal elderly with high β-amyloid deposition , 2012, Neurology.

[14]  M. Mattson,et al.  Soluble amyloid precursor protein-α modulates β-secretase activity and amyloid-β generation , 2012, Nature Communications.

[15]  Felicita Pedata,et al.  Cognitive impairment with vascular impairment and degeneration. , 2011, Current neurovascular research.

[16]  Smita Majumder,et al.  Inducing Autophagy by Rapamycin Before, but Not After, the Formation of Plaques and Tangles Ameliorates Cognitive Deficits , 2011, Alzheimer's & Dementia.

[17]  Ting Zhang,et al.  3-n-butylphthalide (NBP) attenuated neuronal autophagy and amyloid-beta expression in diabetic mice subjected to brain ischemia , 2011, Neurological research.

[18]  D. Rubinsztein,et al.  Regulation of mammalian autophagy in physiology and pathophysiology. , 2010, Physiological reviews.

[19]  Rena Li,et al.  Genetic Targeting Aromatase in Male Amyloid Precursor Protein Transgenic Mice Down-Regulates β-Secretase (BACE1) and Prevents Alzheimer-Like Pathology and Cognitive Impairment , 2010, The Journal of Neuroscience.

[20]  Joseph V. Hajnal,et al.  A robust method to estimate the intracranial volume across MRI field strengths (1.5T and 3T) , 2010, NeuroImage.

[21]  G. Tsokos,et al.  Decay accelerating factor (CD55) protects neuronal cells from chemical hypoxia-induced injury , 2010, Journal of Neuroinflammation.

[22]  J. Pouysségur,et al.  Hypoxia-induced autophagy: cell death or cell survival? , 2010, Current opinion in cell biology.

[23]  Jayanta Debnath,et al.  Inhibition of mTOR by Rapamycin Abolishes Cognitive Deficits and Reduces Amyloid-β Levels in a Mouse Model of Alzheimer's Disease , 2010, PloS one.

[24]  N. Mizushima,et al.  Methods in Mammalian Autophagy Research , 2010, Cell.

[25]  G. Semenza.  Defining the role of hypoxia-inducible factor 1 in cancer biology and therapeutics , 2010, Oncogene.

[26]  S. Pendlebury,et al.  Prevalence, incidence, and factors associated with pre-stroke and post-stroke dementia: a systematic review and meta-analysis , 2009, The Lancet Neurology.

[27]  Ralph A. Nixon,et al.  Autophagy Induction and Autophagosome Clearance in Neurons: Relationship to Autophagic Pathology in Alzheimer's Disease , 2008, The Journal of Neuroscience.

[28]  Daniel J. Klionsky,et al.  Autophagy fights disease through cellular self-digestion , 2008, Nature.

[29]  John L Cleveland,et al.  Guidelines for the use and interpretation of assays for monitoring autophagy in higher eukaryotes , 2008, Autophagy.

[30]  Guido Kroemer,et al.  Autophagy in the Pathogenesis of Disease , 2008, Cell.

[31]  Manuel Buttini,et al.  Partial Reduction of BACE1 Has Dramatic Effects on Alzheimer Plaque and Synaptic Pathology in APP Transgenic Mice* , 2007, Journal of Biological Chemistry.

[32]  Jiankun Cui,et al.  Hypoxia-inducible Factor 1α (HIF-1α)-mediated Hypoxia Increases BACE1 Expression and β-Amyloid Generation* , 2007, Journal of Biological Chemistry.

[33]  M. Ohno,et al.  BACE1 gene deletion prevents neuron loss and memory deficits in 5XFAD APP/PS1 transgenic mice , 2007, Neurobiology of Disease.

[34]  Hong Qing,et al.  Hypoxia facilitates Alzheimer's disease pathogenesis by up-regulating BACE1 gene expression , 2006, Proceedings of the National Academy of Sciences.

[35]  H. Cai,et al.  BACE1, a Major Determinant of Selective Vulnerability of the Brain to Amyloid-β Amyloidogenesis, is Essential for Cognitive, Emotional, and Synaptic Functions , 2005, The Journal of Neuroscience.

[36]  L. Tjernberg,et al.  Macroautophagy—a novel β-amyloid peptide-generating pathway activated in Alzheimer's disease , 2005, The Journal of cell biology.

[37]  B. Hyman,et al.  BACE Is Degraded via the Lysosomal Pathway* , 2005, Journal of Biological Chemistry.

[38]  M. Ohno,et al.  BACE1 Deficiency Rescues Memory Deficits and Cholinergic Dysfunction in a Mouse Model of Alzheimer's Disease , 2004, Neuron.

[39]  D. Attaix,et al.  Class III phosphoinositide 3-kinase--Beclin1 complex mediates the amino acid-dependent regulation of autophagy in C2C12 myotubes. , 2003, The Biochemical journal.

[40]  D. Leys,et al.  Poststroke dementia , 2001, Neurology.

[41]  R. Vassar.  The beta-secretase, BACE: a prime drug target for Alzheimer's disease. , 2001, Journal of molecular neuroscience : MN.

[42]  D. Small,et al.  Regulation of APP cleavage by α‐, β‐ and γ‐secretases , 2000 .

[43]  G. Semenza,et al.  Modulation of hypoxia-inducible factor 1alpha expression by the epidermal growth factor/phosphatidylinositol 3-kinase/PTEN/AKT/FRAP pathway in human prostate cancer cells: implications for tumor angiogenesis and therapeutics. , 2000, Cancer research.

[44]  M. Moskowitz,et al.  Pathobiology of ischaemic stroke: an integrated view , 1999, Trends in Neurosciences.

[45]  V. Hachinski,et al.  Cerebrovascular Pathology in Alzheimer's Disease: Cause, Effect or Epiphenomenon? , 1997, Annals of the New York Academy of Sciences.

[46]  M. Goldberg,et al.  Combined oxygen and glucose deprivation in cortical cell culture: calcium-dependent and calcium-independent mechanisms of neuronal injury , 1993, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[47]  Jiankun Cui,et al.  Hypoxia-inducible factor 1alpha (HIF-1alpha)-mediated hypoxia increases BACE1 expression and beta-amyloid generation. , 2007, The Journal of biological chemistry.

[48]  R. Vassar.  beta-Secretase, APP and Abeta in Alzheimer's disease. , 2005, Sub-cellular biochemistry.

[49]  R. Vassar.  β-Secretase, APP and Aβ in Alzheimer’s Disease , 2005 .

[50]  D. Small,et al.  Regulation of APP cleavage by alpha-, beta- and gamma-secretases. , 2000, FEBS letters.

[51]  N. Saunders.  Neural regeneration research , 1999 .

[52]  D. Rubinsztein,et al.  Regulation of Mammalian Autophagy in Physiology and Pathophysiology , 2022 .

[53]  K. Blomgren,et al.  Guidelines for the use and interpretation of assays for monitoring cell death in higher eukaryotes , 2009, Cell Death and Differentiation.