Neuron-specific non-classical release of prothymosin alpha: a novel neuroprotective damage-associated molecular patterns
Neuron-specific non-classical release of prothymosin alpha: a novel neuroprotective damage-associated molecular patterns
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DOI：
10.1111/j.1471-4159.2012.07897.x
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发表时间：
2012-10-01
影响因子：
4.7
通讯作者：
Ueda, Hiroshi
中科院分区：
文献类型：
--
作者：
Halder, Sebok Kumar;Matsunaga, Hayato;Ueda, Hiroshi
Prothymosin alpha (ProTa), a nuclear protein devoid of signal sequence, has been shown to possess a number of cellular functions including cell survival. Most recently, we demonstrated that ProTa is localized in the nuclei of neurons, while it is found in both nuclei and cytoplasm in the astrocytes and microglia of adult brain. However, the cell type-specific non-classical release of ProTa under cerebral ischemia is yet unknown. In this study, we report that ProTa is non-classically released along with S100A13 from neurons in the hippocampus, striatum and somatosensory cortex at 3 similar to h after cerebral ischemia, but amlexanox (an anti-allergic compound) reversibly blocks this neuronal ProTa release. We found that none of ProTa is released from astrocytes and microglia under ischemic stress. Indeed, ProTa intensity is increased gradually in astrocytes and microglia through 24 similar to h after the cerebral ischemia. Interestingly, Z-Val-Ala-Asp fluoromethyl ketone, a caspase 3 inhibitor, pre-treatment induces ProTa release from astrocytes in the ischemic brain, but this release is reversibly blocked by amlexanox. However, Z-Val-Ala-Asp fluoromethyl ketone as well as amlexanox has no effect on ProTa distribution in microglia upon cerebral ischemia. Taken together, these results suggest that only neurons have machineries to release ProTa upon cerebral ischemic stress in vivo.
