PDF(Pubmed)
Abstract：
UNASSIGNED: White matter damage (WMD) is linked to both cerebral palsy and cognitive deficits in infants born prematurely. The focus of this study was to examine how caffeine influences the acetylation of proteins within the neonatal white matter and to evaluate its effectiveness in treating white matter damage caused by hypoxia-ischemia.
UNASSIGNED: We employed a method combining affinity enrichment with advanced liquid chromatography and mass spectrometry to profile acetylation in proteins from the white matter of neonatal rats grouped into control (Sham), hypoxic-ischemic (HI), and caffeine-treated (Caffeine) groups.
UNASSIGNED: Our findings included 1,999 sites of lysine acetylation across 1,123 proteins, with quantifiable changes noted in 1,342 sites within 689 proteins. Analysis of these patterns identified recurring sequences adjacent to the acetylation sites, notably YKacN, FkacN, and G * * * GkacS. Investigation into the biological roles of these proteins through Gene Ontology analysis indicated their involvement in a variety of cellular processes, predominantly within mitochondrial locations. Further analysis indicated that the acetylation of tau (Mapt), a protein associated with microtubules, was elevated in the HI condition; however, caffeine treatment appeared to mitigate this over-modification, thus potentially aiding in reducing oxidative stress, inflammation in the nervous system, and improving mitochondrial health. Caffeine inhibited acetylated Mapt through sirtuin 2 (SITR2), promoted Mapt nuclear translocation, and improved mitochondrial dysfunction, which was subsequently weakened by the SIRT2 inhibitor, AK-7.
UNASSIGNED: Caffeine-induced changes in lysine acetylation may play a key role in improving mitochondrial dysfunction and inhibiting oxidative stress and neuroinflammation.
UNASSIGNED: We employed a method combining affinity enrichment with advanced liquid chromatography and mass spectrometry to profile acetylation in proteins from the white matter of neonatal rats grouped into control (Sham), hypoxic-ischemic (HI), and caffeine-treated (Caffeine) groups.
UNASSIGNED: Our findings included 1,999 sites of lysine acetylation across 1,123 proteins, with quantifiable changes noted in 1,342 sites within 689 proteins. Analysis of these patterns identified recurring sequences adjacent to the acetylation sites, notably YKacN, FkacN, and G * * * GkacS. Investigation into the biological roles of these proteins through Gene Ontology analysis indicated their involvement in a variety of cellular processes, predominantly within mitochondrial locations. Further analysis indicated that the acetylation of tau (Mapt), a protein associated with microtubules, was elevated in the HI condition; however, caffeine treatment appeared to mitigate this over-modification, thus potentially aiding in reducing oxidative stress, inflammation in the nervous system, and improving mitochondrial health. Caffeine inhibited acetylated Mapt through sirtuin 2 (SITR2), promoted Mapt nuclear translocation, and improved mitochondrial dysfunction, which was subsequently weakened by the SIRT2 inhibitor, AK-7.
UNASSIGNED: Caffeine-induced changes in lysine acetylation may play a key role in improving mitochondrial dysfunction and inhibiting oxidative stress and neuroinflammation.
摘要：
■白质损伤（WMD）与早产婴儿的脑瘫和认知障碍有关。这项研究的重点是研究咖啡因如何影响新生儿白质内蛋白质的乙酰化，并评估其治疗缺氧缺血引起的白质损伤的有效性。
■我们采用了一种将亲和富集与高级液相色谱和质谱联用的方法来分析新生大鼠白质蛋白质中的乙酰化，这些蛋白质被分组为对照（Sham）。缺氧缺血（HI），和咖啡因治疗（咖啡因）组。
■我们的发现包括1,123种蛋白质的1,999个赖氨酸乙酰化位点，在689种蛋白质中的1342个位点中记录到可量化的变化。对这些模式的分析确定了与乙酰化位点相邻的重复序列，尤其是YKacN,FkacN,和G***GkacS。通过基因本体论分析研究这些蛋白质的生物学作用表明它们参与了各种细胞过程，主要在线粒体位置。进一步分析表明，tau(Mapt)的乙酰化，与微管相关的蛋白质，在HI条件下升高；然而，咖啡因治疗似乎减轻了这种过度修饰，因此可能有助于减少氧化应激，神经系统的炎症，改善线粒体健康。咖啡因通过沉默酶2（SITR2）抑制乙酰化Mapt，促进Mapt核易位，和改善线粒体功能障碍，随后被SIRT2抑制剂削弱，AK-7
■咖啡因诱导的赖氨酸乙酰化变化可能在改善线粒体功能障碍以及抑制氧化应激和神经炎症中起关键作用。
■我们采用了一种将亲和富集与高级液相色谱和质谱联用的方法来分析新生大鼠白质蛋白质中的乙酰化，这些蛋白质被分组为对照（Sham）。缺氧缺血（HI），和咖啡因治疗（咖啡因）组。
■我们的发现包括1,123种蛋白质的1,999个赖氨酸乙酰化位点，在689种蛋白质中的1342个位点中记录到可量化的变化。对这些模式的分析确定了与乙酰化位点相邻的重复序列，尤其是YKacN,FkacN,和G***GkacS。通过基因本体论分析研究这些蛋白质的生物学作用表明它们参与了各种细胞过程，主要在线粒体位置。进一步分析表明，tau(Mapt)的乙酰化，与微管相关的蛋白质，在HI条件下升高；然而，咖啡因治疗似乎减轻了这种过度修饰，因此可能有助于减少氧化应激，神经系统的炎症，改善线粒体健康。咖啡因通过沉默酶2（SITR2）抑制乙酰化Mapt，促进Mapt核易位，和改善线粒体功能障碍，随后被SIRT2抑制剂削弱，AK-7
■咖啡因诱导的赖氨酸乙酰化变化可能在改善线粒体功能障碍以及抑制氧化应激和神经炎症中起关键作用。
