Abstract
In cultured cerebellar granule cells, the total amount of fodrin alpha subunit increased 3-fold between 0 and 10 days in vitro and fodrin mRNA increased 5-fold. The exposure of cerebellar neurons to NMDA induced the accumulation of a 150 kd proteolytic fragment of fodrin. The NMDA-induced breakdown of fodrin was time-, concentration-, and Ca2(+)-dependent and was inhibited by APV, Mg2+, or the calpain I inhibitor N-acetyl-Leu-Leu-norleucinal. Kainate caused fodrin proteolysis through indirect activation of NMDA receptors. Quisqualate was ineffective. The NMDA-induced degradation of fodrin occurred under conditions that did not cause degeneration of cultured cerebellar neurons. These results show that Ca2+/calpain I-dependent proteolysis of fodrin is selectively associated with NMDA receptor activation; however, fodrin proteolysis per se does not play a causal role in NMDA-induced toxicity in cerebellar granule cells.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Blotting, Northern
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Calcium / pharmacology
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Calcium Channels / drug effects
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Calcium Channels / physiology
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Calpain / pharmacology
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Carrier Proteins / genetics
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Carrier Proteins / metabolism*
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Cattle
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Cells, Cultured
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Cerebellum / cytology
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Cerebellum / drug effects
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Cerebellum / metabolism
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Dose-Response Relationship, Drug
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Fluorescent Antibody Technique
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Kainic Acid / pharmacology
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Leupeptins / pharmacology
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Microfilament Proteins / genetics
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Microfilament Proteins / metabolism*
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N-Methylaspartate / toxicity*
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Neurons / drug effects
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Neurons / metabolism*
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RNA, Messenger / drug effects
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RNA, Messenger / genetics
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RNA, Messenger / metabolism
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Receptors, Glutamate
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Receptors, N-Methyl-D-Aspartate / drug effects
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Receptors, N-Methyl-D-Aspartate / physiology
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Receptors, Neurotransmitter / drug effects
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Receptors, Neurotransmitter / physiology
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Time Factors
Substances
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Calcium Channels
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Carrier Proteins
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Leupeptins
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Microfilament Proteins
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RNA, Messenger
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Receptors, Glutamate
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Receptors, N-Methyl-D-Aspartate
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Receptors, Neurotransmitter
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fodrin
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acetylleucyl-leucyl-norleucinal
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N-Methylaspartate
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Calpain
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Kainic Acid
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Calcium