Effects of positive AMPA receptor modulators on calpain-mediated spectrin degradation in cultured hippocampal slices

Jourdi, Hussam; Yanagihara, Ted K.; Martinez, Ulises; Bi, Xiaoning; Lynch, Gary; Baudry, Michel

doi:10.1016/j.neuint.2004.07.002

Cited by 24 publications

(32 citation statements)

References 55 publications

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“…Recently, we showed a gradual accumulation of CX614-induced calpain-mediated spectrin breakdown products that was completely blocked by calpain inhibitor III and by the AMPAr blocker CNQX but unaffected by the NMDAr blocker AP-5 (Jourdi et al, 2005). In the present study, decreases in levels of AMPAr subunits and of their respective anchoring PDZ proteins were significant after 4 h of CX614 treatment and became greater with longer incubation intervals.…”

Section: Discussionsupporting

confidence: 68%

“…Our results clearly show that calpain activation is predominantly downstream from AMPAr and that it mediates CX614-induced AMPAr protein loss and degradation of PDZ proteins and spectrin (Jourdi et al, 2005). In particular, calpain inhibition blocked CX614-induced decrease in PDZ protein levels and formation of PDZ protein degradation products, and it blocked CX614 effects on AMPAr subunits.…”

Section: Discussionmentioning

confidence: 52%

“…Preliminary results showed that probing brain membrane fractions pretreated with Ca 2ϩ (2 mM and 30 min at 37°C, conditions that activate endogenous calpain) with anti-GRIP1 antibodies showed bands that migrated at the same level as those generated after treatment of cultured hippocampal slices with CX614 (data not shown). Moreover, we recently reported that CX614 treatment activates calpain and leads to the degradation of the cytoskeletal protein spectrin (Jourdi et al, 2005). These results suggested that prolonged treatment with CX614 could result in calpainmediated SAP97 and GRIP1 degradation, thereby leading to AMPAr down-regulation by interfering with PDZ proteindependent stabilization and/or intracellular AMPAr trafficking.…”

Section: Treatment Of Cultured Hippocampal Slices With Cx614 Induces mentioning

confidence: 93%

“…Ten-to 12-day-old rat pups were obtained from The Jackson Laboratory (Bar Harbor, ME) and used to prepare hippocampal slice cultures as described previously (Jourdi et al, 2005). Briefly, animals were decapitated, and the brains were dissected, trimmed, and 400-m-thick hippocampal slices were cut using a McIllwain tissue slicer (Fotodyne Inc., New Berlin, WI).…”

Section: Methodsmentioning

confidence: 99%

“…Moreover, calpain truncates the C-terminal domains of several AMPA and NMDA receptor subunits, as well as PSD-95 and GRIP1, members of the PDZ family of proteins (Lu et al, 2000, and the cytoskeletal protein spectrin (Baudry and Lynch, 1981). In a recent report, we showed that prolonged incubation of cultured hippocampal slices with CX614 resulted in calpain activation and calpain-mediated proteolysis of spectrin (Jourdi et al, 2005). Together, these studies indicate that calpain plays a critical role in the reorganization of glutamatergic postsynaptic compartment after a number of stimuli, resulting in increased calcium concentrations in postsynaptic structures.…”

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confidence: 96%

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Prolonged Positive Modulation of α-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid (AMPA) Receptors Induces Calpain-Mediated PSD-95/Dlg/ZO-1 Protein Degradation and AMPA Receptor Down-Regulation in Cultured Hippocampal Slices

Jourdi

Lü²,

Yanagihara³

et al. 2005

J Pharmacol Exp Ther

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Prolonged exposure of cultured hippocampal slices to CX614 [2H,3H,6aH-pyrrolidino[2Љ,1Љ-3Ј,2Ј]1,3-oxazino[6Ј,5Ј-5,4]-benzo[e]1,4-dioxan 10-one], a positive ␣-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor (AMPAr) modulator, decreases receptor response to synaptic stimulation, an effect that could reflect reduced receptor expression. The present study investigates this down-regulation and its underlying mechanisms using cultured rat hippocampal slices. Chronic treatment with CX614 gradually reduced levels of glutamate receptor (GluR)1 and GluR2/3 AMPAr subunits and of their anchoring proteins synapse-associated protein 97 (SAP97) and glutamate receptor interacting protein 1 (GRIP1) through 48 h. Decline in SAP97 and GRIP1 levels was associated with increased abundance of lower molecular weight bands, suggesting degradation of these proteins. CX614 effects were partially reversible after drug removal. GluR1 and GluR2/3 down-regulation and their slow recovery were associated with similar changes in SAP97 and GRIP1 levels. Treatment with CX614 for 48 h significantly reduced AMPAr mRNA levels in hippocampus, whereas 8-h exposure did not. Blockade of ionotropic glutamate receptors prevented CX614-induced decrease in AMPAr subunits and mRNA, with regional selectivity, although an AMPAr blocker was more efficacious than an N-methyl-D-aspartate receptor blocker. Blockade of calpain activity reduced CX614-induced degradation of SAP97 and GRIP1 and prevented decreases in AMPAr subunit but not mRNA levels. Treatment with CX614 alone or in combination with glutamate receptor blockers or calpain inhibitor III did not modify lactate dehydrogenase release into culture medium, implying the absence of cell toxicity. We conclude that CX614-induced AMPAr protein loss is primarily mediated by AMPAr activation and involves calpain-dependent proteolysis of SAP97 and GRIP1. CX614-induced suppression of AMPAr gene expression is, however, calpain-independent, and all these effects are not associated with cell damage.AMPA-type glutamate receptors (AMPAr) mediate most of the fast excitatory neurotransmission in the mammalian central nervous system. Several recent studies have implicated the cycling of these receptors into and out of the synaptic compartment in important neurophysiological phenomena such as long-term potentiation (LTP) and long-term depression (LTD) in support of our initial hypothesis (Baudry and

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Section: Discussionsupporting

confidence: 68%

Section: Discussionmentioning

confidence: 52%

Section: Treatment Of Cultured Hippocampal Slices With Cx614 Induces mentioning

confidence: 93%

Section: Methodsmentioning

confidence: 99%

mentioning

confidence: 96%

See 3 more Smart Citations

Prolonged Positive Modulation of α-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid (AMPA) Receptors Induces Calpain-Mediated PSD-95/Dlg/ZO-1 Protein Degradation and AMPA Receptor Down-Regulation in Cultured Hippocampal Slices

Jourdi

Lü²,

Yanagihara³

et al. 2005

J Pharmacol Exp Ther

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Spectrin and calpain: a ‘target’ and a ‘sniper’ in the pathology of neuronal cells

Czogalla

Sikorski

2005

Cell. Mol. Life Sci.

177

144

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It is well documented that activation of calpain, a calcium-sensitive cysteine protease, marks the pathology of naturally and experimentally occurring neurodegenerative conditions. Calpain-mediated proteolysis of major membrane-skeletal protein, alphaII-spectrin, results in the appearance of two unique and highly stable breakdown products, which is an early event in neural cell pathology. This review focuses on spectrin degradation by calpain within neurons induced by diverse conditions, emphasizing a current picture of multi-pattern neuronal death and a recent success in the development of spectrin-based biomarkers. The issue is presented in the context of the major structural and functional properties of the two proteins.

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Organotypic Hippocampal Slice Cultures: A Model System to Study Basic Cellular and Molecular Mechanisms of Neuronal Cell Death, Neuroprotection, and Synaptic Plasticity

Holopainen

2005

Neurochem Res

101

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The hippocampus has become one of the most extensively studied areas of the mammalian brain, and its proper function is of utmost importance, particularly for learning and memory. The hippocampus is the most susceptible brain region for damage, and its impaired function has been documented in many human brain diseases, e.g. hypoxia, ischemia, and epilepsy regardless of the age of the affected patients. In addition to experimental in vivo models of these disorders, the investigation of basic anatomical, physiological, and molecular aspects requires an adequate experimental in vitro model, which should meet the requirements for well-preserved representation of various cell types, and functional information processing properties in the hippocampus. In this review, the characteristics of organotypic hippocampal slice cultures (OHCs) together with the main differences between the in vivo and in vitro preparations are first briefly outlined. Thereafter, the use of OHCs in studies focusing on neuron cell death and synaptic plasticity is discussed.

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Effects of positive AMPA receptor modulators on calpain-mediated spectrin degradation in cultured hippocampal slices

Cited by 24 publications

References 55 publications

Prolonged Positive Modulation of α-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid (AMPA) Receptors Induces Calpain-Mediated PSD-95/Dlg/ZO-1 Protein Degradation and AMPA Receptor Down-Regulation in Cultured Hippocampal Slices

Prolonged Positive Modulation of α-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid (AMPA) Receptors Induces Calpain-Mediated PSD-95/Dlg/ZO-1 Protein Degradation and AMPA Receptor Down-Regulation in Cultured Hippocampal Slices

Spectrin and calpain: a ‘target’ and a ‘sniper’ in the pathology of neuronal cells

Organotypic Hippocampal Slice Cultures: A Model System to Study Basic Cellular and Molecular Mechanisms of Neuronal Cell Death, Neuroprotection, and Synaptic Plasticity

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