Ammonia induces calpain-dependent cleavage of CRMP-2 during neurite degeneration in primary cultured neurons
| Autor: | Zhenbin Cai, Xiaonan Zhu, Minghui Tan, Fengming Wu, Guowei Zhang, Hongsheng Lin |
|---|---|
| Rok vydání: | 2018 |
| Předmět: |
Aging
Programmed cell death Neurite Primary Cell Culture Nerve Tissue Proteins ammonia Calcium in biology Rats Sprague-Dawley CRMP-2 neurite degeneration medicine Animals Hyperammonemia Cytoskeleton Caspase Neurons biology Chemistry Calpain calpain GSK-3 Cell Biology medicine.disease Cell biology biology.protein Excitatory postsynaptic potential Intercellular Signaling Peptides and Proteins Calcium Research Paper |
| Zdroj: | Aging (Albany NY) |
| ISSN: | 1945-4589 |
| Popis: | Hyperammonemia in the CNS induces irreversible damages to neurons due to ultimate cell loss. Neurite degeneration, a primary event that leads to neuronal cell death, remains less elucidated especially in hyperammonemia circumstances. Here, we found that the administration of ammonia induced neurite degeneration in cultured cerebellar granule neurons. The resulting altered neuronal morphology, rupture of neurites, and disassembly of the cytoskeleton led to cell death. Calcein and Fluo-4 staining revealed that ammonia induced intracellular calcium dysregulation. Subsequently activated calpain cleaved CRMP-2, a microtubule assembly protein. Pharmacologically inhibition of calpain, but not caspases or GSK-3, suppressed the cleavage of CRMP-2 and reversed neurite degeneration under ammonia treatment. Exposure to ammonia decreased whereas inhibition of calpain restored the amplitude and frequency of miniature excitatory postsynaptic currents. These data suggest a mechanism by which elevated ammonia level may induce neuronal dysfunction via abnormal calcium influx and calpain-dependent CRMP-2 cleavage, leading to abnormal synaptic transmission, cytoskeletal collapse, and neurite degeneration. |
| Databáze: | OpenAIRE |
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