BMC Neuroscience BioMed Central

Glutamate-induced apoptosis in neuronal cells is mediated via caspase-dependent and independent mechanisms involving calpain and caspase-3 proteases as well as apoptosis inducing factor (AIF) and this process is inhibited by equine estrogens Abstract Background: Glutamate, a major excitatory amino acid neurotransmitter, causes apoptotic neuronal cell death at high concentrations. Our previous studies have shown that depending on the neuronal cell type, glutamate-induced apoptotic cell death was associated with regulation of genes such as Bcl-2, Bax, and/or caspase-3 and mitochondrial cytochrome c. To further delineate the intracellular mechanisms, we have investigated the role of calpain, an important calcium-dependent protease thought to be involved in apoptosis along with mitochondrial apoptosis inducing factor (AIF) and caspase-3 in primary cortical cells and a mouse hippocampal cell line HT22.

[1]  B. Bhavnani,et al.  Protection of cortical cells by equine estrogens against glutamate-induced excitotoxicity is mediated through a calcium independent mechanism , 2005, BMC Neuroscience.

[2]  B. Bhavnani,et al.  Glutamate-induced apoptosis in primary cortical neurons is inhibited by equine estrogens via down-regulation of caspase-3 and prevention of mitochondrial cytochrome c release , 2005, BMC Neuroscience.

[3]  N. Rothwell,et al.  Cleavage of the Plasma Membrane Na+/Ca2+ Exchanger in Excitotoxicity , 2005, Cell.

[4]  R. Vink,et al.  Anandamide-induced cell death in primary neuronal cultures: role of calpain and caspase pathways , 2004, Cell Death and Differentiation.

[5]  E. Sribnick,et al.  17β‐estradiol attenuates glutamate‐induced apoptosis and preserves electrophysiologic function in primary cortical neurons , 2004 .

[6]  A. Rami,et al.  Ischemic neuronal death in the rat hippocampus: the calpain–calpastatin–caspase hypothesis , 2003, Neurobiology of Disease.

[7]  B. Bhavnani.  Estrogens and menopause: pharmacology of conjugated equine estrogens and their potential role in the prevention of neurodegenerative diseases such as Alzheimer’s , 2003, The Journal of Steroid Biochemistry and Molecular Biology.

[8]  N. Banik,et al.  Calpain and its involvement in the pathophysiology of CNS injuries and diseases: therapeutic potential of calpain inhibitors for prevention of neurodegeneration. , 2003, Current drug targets. CNS and neurological disorders.

[9]  E. Sribnick,et al.  Estrogen attenuates oxidative stress-induced apoptosis in C6 glial cells , 2003, Brain Research.

[10]  H. Nakanishi,et al.  Activation of mu-calpain in developing cortical neurons following methylmercury treatment. , 2003, Brain research. Developmental brain research.

[11]  M. Yamaguchi,et al.  Possible contribution of apoptosis‐inducing factor (AIF) and reactive oxygen species (ROS) to UVB‐induced caspase‐independent cell death in the T cell line Jurkat , 2003, Journal of leukocyte biology.

[12]  G. Kroemer,et al.  Apoptosis-inducing factor (AIF): key to the conserved caspase-independent pathways of cell death? , 2002, Journal of Cell Science.

[13]  E. Hogan,et al.  Molecular evidence of apoptotic death in malignant brain tumors including glioblastoma multiforme: Upregulation of calpain and caspase‐3 , 2002, Journal of neuroscience research.

[14]  Simon C Watkins,et al.  Intranuclear localization of apoptosis‐inducing factor (AIF) and large scale dna fragmentation after traumatic brain injury in rats and in neuronal cultures exposed to peroxynitrite , 2002, Journal of neurochemistry.

[15]  Kevin K W Wang,et al.  Selective Release of Calpain Produced αII-Spectrin (α-Fodrin) Breakdown Products by Acute Neuronal Cell Death , 2002 .

[16]  W. Robberecht,et al.  An α-mercaptoacrylic acid derivative (PD150606) inhibits selective motor neuron death via inhibition of kainate-induced Ca2+ influx and not via calpain inhibition , 2002, Neuropharmacology.

[17]  N. Rothwell,et al.  Involvement of caspases and calpains in cerebrocortical neuronal cell death is stimulus‐dependent , 2002, British journal of pharmacology.

[18]  G. Kroemer,et al.  Apoptosis-inducing factor (AIF): a novel caspase-independent death effector released from mitochondria. , 2002, Biochimie.

[19]  R. Jemmerson,et al.  Calcium‐induced Cytochrome c release from CNS mitochondria is associated with the permeability transition and rupture of the outer membrane , 2002, Journal of neurochemistry.

[20]  B. Bhavnani,et al.  Comparison of the antioxidant effects of equine estrogens, red wine components, vitamin E, and probucol on low-density lipoprotein oxidation in postmenopausal women , 2001, Menopause.

[21]  B. Pike,et al.  Concurrent Assessment of Calpain and Caspase-3 Activation after Oxygen–Glucose Deprivation in Primary Septo-Hippocampal Cultures , 2001, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[22]  B. Bhavnani,et al.  Differential Neuroprotective Effects of Equine Estrogens Against Oxidized Low Density Lipoprotein—Induced Neuronal Cell Death , 2001, The Journal of the Society for Gynecologic Investigation: JSGI.

[23]  E. Marra,et al.  Glutamate neurotoxicity, oxidative stress and mitochondria , 2001, FEBS letters.

[24]  P. Tiidus,et al.  Estrogen effect on post-exercise skeletal muscle neutrophil infiltration and calpain activity. , 2001, Canadian journal of physiology and pharmacology.

[25]  G. Kroemer,et al.  Dominant cell death induction by extramitochondrially targeted apoptosis‐inducing factor , 2001, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[26]  A. Azzariti,et al.  Cytochrome c Is Released from Mitochondria in a Reactive Oxygen Species (ROS)-dependent Fashion and Can Operate as a ROS Scavenger and as a Respiratory Substrate in Cerebellar Neurons Undergoing Excitotoxic Death* , 2000, The Journal of Biological Chemistry.

[27]  M. Duchen.  Mitochondria and calcium: from cell signalling to cell death , 2000, The Journal of physiology.

[28]  B. Pike,et al.  Temporal Profile and Cell Subtype Distribution of Activated Caspase‐3 Following Experimental Traumatic Brain Injury , 2000, Journal of neurochemistry.

[29]  Guido Kroemer,et al.  Apoptosis‐inducing factor (AIF): a ubiquitous mitochondrial oxidoreductase involved in apoptosis , 2000, FEBS letters.

[30]  G. Cole,et al.  Activation of Calpain I Converts Excitotoxic Neuron Death into a Caspase-independent Cell Death* , 2000, The Journal of Biological Chemistry.

[31]  A. Rami,et al.  μ-Calpain activation, DNA fragmentation, and synergistic effects of caspase and calpain inhibitors in protecting hippocampal neurons from ischemic damage , 2000, Brain Research.

[32]  Kyong-Tai Kim,et al.  Nongenomic Inhibition of Catecholamine Secretion by 17β‐Estradiol in PC12 Cells , 2000, Journal of neurochemistry.

[33]  B. Pike,et al.  Stretch injury causes calpain and caspase-3 activation and necrotic and apoptotic cell death in septo-hippocampal cell cultures. , 2000, Journal of neurotrauma.

[34]  Kevin K. W Wang,et al.  Calpain and caspase: can you tell the difference? , 2000, Trends in Neurosciences.

[35]  J. Simpkins,et al.  Glutamate Receptor Requirement for Neuronal Death from Anoxia–Reoxygenation: An in Vitro Model for Assessment of the Neuroprotective Effects of Estrogens , 1999, Cellular and Molecular Neurobiology.

[36]  L. Gollapudi,et al.  Estrogen and NGF synergistically protect terminally differentiated, ERα‐transfected PC12 cells from apoptosis , 1999, Journal of neuroscience research.

[37]  M. Matsuzaki,et al.  Calpain inhibitor-1 reduces infarct size and DNA fragmentation of myocardium in ischemic/reperfused rat heart. , 1999, Journal of cardiovascular pharmacology.

[38]  R. L. Hayes,et al.  Maitotoxin Induces Calpain But Not Caspase-3 Activation and Necrotic Cell Death in Primary Septo-Hippocampal Cultures , 1999, Neurochemical Research.

[39]  Ruedi Aebersold,et al.  Molecular characterization of mitochondrial apoptosis-inducing factor , 1999, Nature.

[40]  R. DeBiasi,et al.  Reovirus-Induced Apoptosis Is Preceded by Increased Cellular Calpain Activity and Is Blocked by Calpain Inhibitors , 1999, Journal of Virology.

[41]  J. Simpkins,et al.  Estrogen attenuates over-expression of β-amyloid precursor protein messager RNA in an animal model of focal ischemia , 1998, Brain Research.

[42]  P. Maher,et al.  Phosphatidylcholine-specific phospholipase C regulates glutamate-induced nerve cell death. , 1998, Proceedings of the National Academy of Sciences of the United States of America.

[43]  G. Mor,et al.  Raloxifene Induces Neurite Outgrowth in, Estrogen Receptor Positive PC 12 Cells , 1998, Menopause.

[44]  B. Pettmann,et al.  Calpain inhibitors, but not caspase inhibitors, prevent actin proteolysis and DNA fragmentation during apoptosis. , 1998, Journal of cell science.

[45]  R. Nixon,et al.  Calpain I activation in rat hippocampal neurons in culture is NMDA receptor selective and not essential for excitotoxic cell death. , 1998, Brain research. Molecular brain research.

[46]  A. Yakovlev,et al.  Activation of CPP32-Like Caspases Contributes to Neuronal Apoptosis and Neurological Dysfunction after Traumatic Brain Injury , 1997, The Journal of Neuroscience.

[47]  R. Gilbertsen,et al.  Non-erythroid alpha-spectrin breakdown by calpain and interleukin 1 beta-converting-enzyme-like protease(s) in apoptotic cells: contributory roles of both protease families in neuronal apoptosis. , 1996, The Biochemical journal.

[48]  A. Chinnaiyan,et al.  ICE-LAP6, a Novel Member of the ICE/Ced-3 Gene Family, Is Activated by the Cytotoxic T Cell Protease Granzyme B* , 1996, The Journal of Biological Chemistry.

[49]  D. Dorsa,et al.  Estrogen protects primary cortical neurons from glutamate toxicity , 1996, Neuroscience Letters.

[50]  M. Mattson,et al.  Estrogens Attenuate and Corticosterone Exacerbates Excitotoxicity, Oxidative Injury, and Amyloid β‐Peptide Toxicity in Hippocampal Neurons , 1996, Journal of neurochemistry.

[51]  F. Holsboer,et al.  17-beta estradiol protects neurons from oxidative stress-induced cell death in vitro. , 1995, Biochemical and biophysical research communications.

[52]  A. Malkinson,et al.  Calpain activation in apoptosis , 1994, Journal of cellular physiology.

[53]  D. Duval,et al.  Cytotoxic effects of glutamic acid on PC12 cells , 1994, Neurochemistry International.

[54]  Z. Rymaszewski,et al.  Antioxidant potential of specific estrogens on lipid peroxidation. , 1994, The Journal of clinical endocrinology and metabolism.

[55]  J. Coyle,et al.  Oxidative stress, glutamate, and neurodegenerative disorders. , 1993, Science.

[56]  A. Guidotti,et al.  Glutamate Neurotoxicity Is Independent of Calpain I Inhibition in Primary Cultures of Cerebellar Granule Cells , 1991, Journal of neurochemistry.

[57]  F. Di Virgilio,et al.  Structural and functional aspects of calcium homeostasis in eukaryotic cells. , 1990, European journal of biochemistry.

[58]  T. Murphy,et al.  Glutamate toxicity in a neuronal cell line involves inhibition of cystine transport leading to oxidative stress , 1989, Neuron.

[59]  R. Siman,et al.  Calpain I activation is specifically related to excitatory amino acid induction of hippocampal damage , 1989, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[60]  F. Fukai,et al.  Action of calpain on the basic estrogen receptor molecule of porcine uterus. , 1984, Journal of biochemistry.

[61]  J. Gustafsson,et al.  Comparison of the ligand binding specificity and transcript tissue distribution of estrogen receptors alpha and beta. , 1997, Endocrinology.

[62]  A. Sevanian,et al.  Cardioprotective effects of individual conjugated equine estrogens through their possible modulation of insulin resistance and oxidation of low-density lipoprotein. , 1997, Fertility and sterility.