論文 - 詳細
| RRC ID | 81327 |
|---|---|
| 著者 | Murata H, Yasui Y, Oiso K, Ochi T, Tomonobu N, Yamamoto KI, Kinoshita R, Sakaguchi M. |
| タイトル | STAT1/3 signaling suppresses axon degeneration and neuronal cell death through regulation of NAD+-biosynthetic and consuming enzymes. |
| ジャーナル | Cell Signal |
| Abstract |
Nicotinamide adenine dinucleotide (NAD)+-biosynthetic and consuming enzymes are involved in various intracellular events through the regulation of NAD+ metabolism. Recently, it has become clear that alterations in the expression of NAD+-biosynthetic and consuming enzymes contribute to the axonal stability of neurons. We explored soluble bioactive factor(s) that alter the expression of NAD+-metabolizing enzymes and found that cytokine interferon (IFN)-γ increased the expression of nicotinamide nucleotide adenylyltransferase 2 (NMNAT2), an NAD+-biosynthetic enzyme. IFN-γ activated signal transducers and activators of transcription 1 and 3 (STAT1/3) followed by c-Jun N-terminal kinase (JNK) suppression. As a result, STAT1/3 increased the expression of NMNAT2 at both mRNA and protein levels in a dose- and time-dependent manner and, at the same time, suppressed activation of sterile alpha and Toll/interleukin receptor motif-containing 1 (SARM1), an NAD+-consuming enzyme, and increased intracellular NAD+ levels. We examined the protective effect of STAT1/3 signaling against vincristine-mediated cell injury as a model of chemotherapy-induced peripheral neuropathy (CIPN), in which axonal degeneration is involved in disease progression. We found that IFN-γ-mediated STAT1/3 activation inhibited vincristine-induced downregulation of NMNAT2 and upregulation of SARM1 phosphorylation, resulting in modest suppression of subsequent neurite degradation and cell death. These results indicate that STAT1/3 signaling induces NMNAT2 expression while simultaneously suppressing SARM1 phosphorylation, and that both these actions contribute to suppression of axonal degeneration and cell death. |
| 巻・号 | 108 |
| ページ | 110717 |
| 公開日 | 2023-8-1 |
| DOI | 10.1016/j.cellsig.2023.110717 |
| PII | S0898-6568(23)00131-6 |
| PMID | 37187216 |
| MeSH | Armadillo Domain Proteins / metabolism Axons* / metabolism Cell Death NAD* / metabolism Neurons / metabolism Vincristine / metabolism |
| IF | 3.968 |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 最多言及媒体 | X(Twitter) |
| 各媒体での言及数の合計 | 1 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| ヒト・動物細胞 | 201B7(HPS0063) |