Pituitary adenylate cyclase-activating polypeptide attenuates mitochondria-mediated oxidative stress and neuronal apoptosis after subarachnoid hemorrhage in rats.
Pituitary adenylate cyclase-activating polypeptide attenuates mitochondria-mediated oxidative stress and neuronal apoptosis after subarachnoid hemorrhage in rats.
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垂体腺苷酸环化酶激活多肽减轻大鼠蛛网膜下腔出血后线粒体介导的氧化应激和神经元凋亡
DOI：
10.1016/j.freeradbiomed.2021.08.011
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发表时间：
2021-10
影响因子：
7.4
通讯作者：
Zhang J
中科院分区：
文献类型：
--
作者：
Fang Y;Shi H;Huang L;Ren R;Lenahan C;Xiao J;Liu Y;Liu R;Sanghavi R;Li C;Chen S;Tang J;Yu J;Zhang JH;Zhang J
线粒体介导的氧化应激和神经元凋亡在蛛网膜下腔出血（SAH）后早期脑损伤中起重要作用。腺苷酸环化酶激活多肽（PACAP）已被证明可以减少氧化应激和细胞凋亡，维持线粒体功能的压力。本研究的目的是研究PACAP对体内和体外SAH模型中线粒体功能障碍诱导的氧化应激和神经元凋亡的影响。使用PACAP敲除CRISPR和外源性PACAP 38来验证PACAP在血管内穿孔诱导的SAH后的大鼠中以及在血红蛋白刺激后的原代神经元培养物中的神经保护作用。结果表明，内源性PACAP基因敲除加重了SAH后24 h大鼠同侧大脑半球线粒体功能障碍介导的ATP减少、活性氧积累和神经元凋亡。外源性PACAP 38治疗通过减弱大鼠SAH后线粒体介导的氧化应激和神经元凋亡提供了短期和长期的神经学益处。一致地，外源性PACAP 38处理在血红蛋白刺激后的原代神经元培养物中表现出类似的神经保护作用。腺苷酸环化酶（AC）或细胞外信号调节激酶（ERK）的药理学抑制部分取消了体内和体外实验性SAH后PACAP 38治疗提供的抗氧化应激和抗凋亡作用，表明AC-环磷酸腺苷（cAMP）-蛋白激酶A（PKA）和ERK通路的参与。总的来说，PACAP 38可以作为一个有前途的治疗策略，减轻SAH后的早期脑损伤。
Mitochondria-mediated oxidative stress and neuronal apoptosis play an important role in early brain injury following subarachnoid hemorrhage (SAH). Pituitary adenylate cyclase-activating polypeptide (PACAP) has been shown to reduce oxidative stress and cellular apoptosis by maintaining mitochondrial function under stress. The objective of this study is to investigate the effects of PACAP on mitochondria dysfunction - induced oxidative stress and neuronal apoptosis in both vivo and vitro models of SAH. PACAP Knockout CRISPR and exogenous PACAP38 were used to verify the neuroprotective effects of PACAP in rats after endovascular perforation - induced SAH as well as in primary neuron culture after hemoglobin stimulation. The results showed that endogenous PACAP knockout aggravated mitochondria dysfunction - mediated ATP reduction, reactive oxygen species accumulation and neuronal apoptosis in ipsilateral hemisphere at 24h after SAH in rats. The exogenous PACAP38 treatment provided both short- and long- term neurological benefits by attenuating mitochondria - mediated oxidative stress and neuronal apoptosis after SAH in rats. Consistently, the exogenous PACAP38 treatment presented similar neuroprotection in the primary neuron culture after hemoglobin stimulation. Pharmacological inhibition of adenylyl cyclase (AC) or extracellular signal-regulated kinase (ERK) partly abolished the anti-oxidative stress and anti-apoptotic effects provided by PACAP38 treatment after the experimental SAH both in vivo and in vitro, suggesting the involvement of the AC-cyclic adenosine monophosphate (cAMP)-protein kinase A (PKA) and ERK pathway. Collectively, PACAP38 may serve as a promising treatment strategy for alleviating early brain injury after SAH.
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影响因子：
11.4
作者：
Mo J;Enkhjargal B;Travis ZD;Zhou K;Wu P;Zhang G;Zhu Q;Zhang T;Peng J;Xu W;Ocak U;Chen Y;Tang J;Zhang J;Zhang JH
通讯作者：
Zhang JH
影响因子：
6.9
作者：
Fujii, Mutsumi;Yan, Junhao;Rolland, William B.;Soejima, Yoshiteru;Caner, Basak;Zhang, John H.
通讯作者：
Zhang, John H.
DOI：
10.1007/s12031-012-9818-1
发表时间：
2012-11
期刊：
Journal of molecular neuroscience : MN
影响因子：
--
作者：
Lazarovici P;Cohen G;Arien-Zakay H;Chen J;Zhang C;Chopp M;Jiang H
通讯作者：
Jiang H
影响因子：
3.5
作者：
Jiang, L.;Wang, W. -H.;Shen, Y. -F.
通讯作者：
Shen, Y. -F.
影响因子：
2.7
作者：
Racz, B.;Gasz, B.;Reglodi, D.
通讯作者：
Reglodi, D.