Proteomic Profile of Carbonylated Proteins Screen Regulation of Apoptosis via CaMK Signaling in Response to Regular Aerobic Exercise

Proteomic Profile of Carbonylated Proteins Screen Regulation of Apoptosis via CaMK Signaling in Response to Regular Aerobic Exercise
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羰基化蛋白质的蛋白质组学谱通过 CaMK 信号传导对定期有氧运动的细胞凋亡调控进行筛选

DOI:
10.1155/2018/2828143
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发表时间:
2018-12
影响因子:
--
通讯作者:
Yin Dazhong
Yin Dazhong
中科院分区:
生物学3区
文献类型:
--
作者:
Liu Wenfeng;Li Li;Kuang Heyu;Xia Yan;Wang Zhiyuan;Liu Shaopeng;Yin Dazhong

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为研究有氧运动对大鼠纹状体羰基化蛋白的影响并筛选其分子靶点,将13月龄雄性SD大鼠随机分为中年安静对照组(M-SED)和有氧运动组(M-EX),每组12只。最大耗氧量(VO 2 max)从50%-55%逐渐增加到65%-70%,共10周。用电喷雾四极杆飞行时间质谱仪鉴定了36个具有修饰氧化位点的羰基化蛋白质(ESI-Q-TOF-MS),包括M-SED组特有的17种羰基化蛋白、钙/钙调蛋白依赖性蛋白激酶II型亚基β(CaMKIIβ)和异质核核糖核蛋白A2/B1(Hnrnpa 2b 1)等,以及19种特异于M-EX组、泛素羧基末端水解酶同工酶L1(UCH-L1)和苹果酸酶等。规律的有氧运动改善行为学和体视学指标,促进细胞凋亡的正常进行(P < 0.01),减轻CaMK Ⅱ β和Hnrnpa 2b 1的羰基化,但诱导UCH-L1的羰基化,并显著上调CaMK Ⅱ β、CaMK Ⅱ α和Vdac 1的表达水平(p < 0.01)和Hnrnpa 2b 1和UCH-L1(p < 0.01),以及磷酸肌醇3-激酶/蛋白激酶B/哺乳动物雷帕霉素靶蛋白途径(PI 3 K/Akt/mTOR)途径相关基因Akt和mTOR。持续10周的规律有氧运动(前6周递增负荷,随后4周恒定负荷)增强了CaMK II β、Hnrnpa 2b 1的羰基化,并通过激活CaMK和磷酸肌醇3-激酶/蛋白激酶B/mTOR信号转导来调节细胞凋亡。它还促进大鼠纹状体的正常凋亡,这可能对神经元具有保护作用。
To research carbonylated proteins and screen molecular targets in the rat striatum on regular aerobic exercise, male Sprague-Dawley rats (13 months old, n = 24) were randomly divided into middle-aged sedentary control (M-SED) and aerobic exercise (M-EX) groups (n = 12 each). Maximum oxygen consumption (VO2max) gradually increased from 50%–55% to 65%–70% for a total of 10 weeks. A total of 36 carbonylated proteins with modified oxidative sites were identified by Electrospray Ionization-Quadrupole-Time of Flight-Mass Spectrometer (ESI-Q-TOF-MS), including 17 carbonylated proteins unique to the M-SED group, calcium/calmodulin-dependent protein kinase type II subunit beta (CaMKIIβ), and heterogeneous nuclear ribonucleoprotein A2/B1 (Hnrnpa2b1), among others, and 19 specific to the M-EX group, ubiquitin carboxyl-terminal hydrolase isozyme L1 (UCH-L1), and malic enzyme, among others. Regular aerobic exercise improved behavioral and stereological indicators, promoted normal apoptosis (P < 0.01), alleviated carbonylation of the CaMKIIβ and Hnrnpa2b1, but induced carbonylation of the UCH-L1, and significantly upregulated the expression levels of CaMKIIβ, CaMKIIα, and Vdac1 (p < 0.01) and Hnrnpa2b1 and UCH-L1 (p < 0.01), as well as the phosphoinositide 3-kinase/protein kinase B/mammalian target of rapamycin pathways (PI3K/Akt/mTOR) pathway-related genes Akt and mTOR. Regular aerobic exercise for 10 weeks (incremental for the first 6 weeks followed by constant loading for 4 weeks) enhanced carbonylation of CaMKIIβ, Hnrnpa2b1, and modulated apoptosis via activation of CaMK and phosphoinositide 3-kinase/protein kinase B/mTOR signaling. It also promoted normal apoptosis in the rat striatum, which may have protective effects in neurons.
DOI: 10.1016/s0162-0908(10)79782-8
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