Prokineticin-2 prevents neuronal cell deaths in a model of traumatic brain injury.
Prokineticin-2 prevents neuronal cell deaths in a model of traumatic brain injury.
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Prokineticin-2 可预防创伤性脑损伤模型中的神经元细胞死亡
DOI：
10.1038/s41467-021-24469-y
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发表时间：
2021-07-09
影响因子：
16.6
通讯作者：
Ji J
中科院分区：
文献类型：
--
作者：
Bao Z;Liu Y;Chen B;Miao Z;Tu Y;Li C;Chao H;Ye Y;Xu X;Sun G;Zhao P;Liu N;Liu Y;Wang X;Lam SM;Kagan VE;Bayır H;Ji J
Prokineticin-2（Prok 2）是一种重要的分泌性蛋白质，可能通过目前尚不清楚的调控机制参与多种急性和慢性神经系统疾病的发病。创伤性脑损伤引起的神经元的初始机械损伤引发多种继发性反应，包括各种细胞死亡程序。其中之一是铁凋亡，这是与失调的铁和硫醇，并最终在致命的脂质过氧化。在这里，我们探讨的调节作用，Prok 2在神经元铁凋亡在体外和体内。我们发现，Prok 2通过抑制脂质过氧化底物花生四烯酸磷脂的生物合成，通过加速F-box only蛋白10（Fbxo 10）驱动的泛素化，长链脂肪酸CoA连接酶4（Acsl 4）的降解和脂质过氧化的抑制来防止神经元细胞死亡。在受控皮质撞击损伤之前注射腺相关病毒-Prok 2的小鼠显示出减少的神经元变性和改善的运动和认知功能，这可以通过Fbxo 10敲低来抑制。我们的研究表明，Prok 2介导的神经元细胞死亡的创伤性脑损伤通过铁凋亡。Prokineticin-2（Prok 2）是一种参与多种生理过程的分泌蛋白。在这里，作者表明，Prok 2可以预防创伤性脑损伤后的神经元细胞铁凋亡，并且在皮质损伤前给予它可以减少神经元变性以及运动和认知障碍。
Prokineticin-2 (Prok2) is an important secreted protein likely involved in the pathogenesis of several acute and chronic neurological diseases through currently unidentified regulatory mechanisms. The initial mechanical injury of neurons by traumatic brain injury triggers multiple secondary responses including various cell death programs. One of these is ferroptosis, which is associated with dysregulation of iron and thiols and culminates in fatal lipid peroxidation. Here, we explore the regulatory role of Prok2 in neuronal ferroptosis in vitro and in vivo. We show that Prok2 prevents neuronal cell death by suppressing the biosynthesis of lipid peroxidation substrates, arachidonic acid-phospholipids, via accelerated F-box only protein 10 (Fbxo10)-driven ubiquitination, degradation of long-chain-fatty-acid-CoA ligase 4 (Acsl4), and inhibition of lipid peroxidation. Mice injected with adeno-associated virus-Prok2 before controlled cortical impact injury show reduced neuronal degeneration and improved motor and cognitive functions, which could be inhibited by Fbxo10 knockdown. Our study shows that Prok2 mediates neuronal cell deaths in traumatic brain injury via ferroptosis. Prokineticin-2 (Prok2) is a secreted protein involved in many physiological processes. Here, the authors show that Prok2 prevents neuronal cell ferroptosis after traumatic brain injury and its administration before cortical injury reduces neuronal degeneration, and motor and cognitive impairments.
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ACSL4 通过塑造细胞脂质成分来决定铁死亡敏感性。
影响因子：
14.8
作者：
Doll S;Proneth B;Tyurina YY;Panzilius E;Kobayashi S;Ingold I;Irmler M;Beckers J;Aichler M;Walch A;Prokisch H;Trümbach D;Mao G;Qu F;Bayir H;Füllekrug J;Scheel CH;Wurst W;Schick JA;Kagan VE;Angeli JP;Conrad M
通讯作者：
Conrad M
影响因子：
64.8
作者：
Cheng, MY;Bullock, CM;Zhou, QY
通讯作者：
Zhou, QY
影响因子：
64.5
作者：
Dixon SJ;Lemberg KM;Lamprecht MR;Skouta R;Zaitsev EM;Gleason CE;Patel DN;Bauer AJ;Cantley AM;Yang WS;Morrison B 3rd;Stockwell BR
通讯作者：
Stockwell BR
影响因子：
16.6
作者：
Ito, Minako;Shichita, Takashi;Okada, Masahiro;Komine, Ritsuko;Noguchi, Yoshiko;Yoshimura, Akihiko;Morita, Rimpei
通讯作者：
Morita, Rimpei
影响因子：
5.3
作者：
Chao, Honglu;Lin, Chao;Ji, Jing
通讯作者：
Ji, Jing