近日,，日本研究人員通過(guò)動(dòng)物實(shí)驗(yàn)發(fā)現(xiàn),，肝臟內(nèi)傳遞基因信息的核苷酸,，按照生物鐘以一定的節(jié)奏合成。研究人員希望據(jù)此開(kāi)發(fā)出將癌癥化療與生物鐘節(jié)奏結(jié)合的治療方法,，改善治療效果。
核苷酸是核酸的基本組成單位,，隨著核酸分布于生物體內(nèi)各器官,、組織和細(xì)胞中，并作為核酸的組成成分參與生物的遺傳,、發(fā)育,、生長(zhǎng)等基本生命活動(dòng)。
京都大學(xué)教授岡村均率領(lǐng)的研究小組在新一期美國(guó)《細(xì)胞—報(bào)告》Cell Reports上發(fā)表論文說(shuō),，他們?cè)趧?dòng)物實(shí)驗(yàn)中使用破壞了肝臟內(nèi)生物鐘的小鼠和正常小鼠,，調(diào)查了核苷酸生成的酶的變化。結(jié)果發(fā)現(xiàn)正常小鼠白天酶的生成量是夜間的四分之一左右,，其量的變化是有規(guī)律的,，大致呈拋物線狀，而體內(nèi)生物鐘被破壞的小鼠,，酶量的變化則是混亂的,。
酶的變化反映了核苷酸量的變化。由于癌癥化療就是通過(guò)改變核苷酸所產(chǎn)生酶的量來(lái)殺死癌細(xì)胞的,，研究人員認(rèn)為,，弄清核苷酸合成的節(jié)奏，有助于在治療癌癥時(shí)選擇最合適的時(shí)機(jī)進(jìn)行化療,，從而改善治療效果并降低副作用,。（生物谷Bioon.com）
doi:10.1016/j.celrep.2012.03.001
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Rhythmic Nucleotide Synthesis in the Liver: Temporal Segregation of Metabolites
Jean-Michel Fustin, Masao Doi, Hiroyuki Yamada, Rie Komatsu, Shigeki Shimba, Hitoshi Okamura
The synthesis of nucleotides in the body is centrally controlled by the liver, via salvage or de novo synthesis. We reveal a pervasive circadian influence on hepatic nucleotide metabolism, from rhythmic gene expression of rate-limiting enzymes to oscillating nucleotide metabolome in wild-type (WT) mice. Genetic disruption of the hepatic clock leads to aberrant expression of these enzymes, together with anomalous nucleotide rhythms, such as constant low levels of ATP with an excess in uric acid, the degradation product of purines. These results clearly demonstrate that the hepatic circadian clock orchestrates nucleotide synthesis and degradation. This circadian metabolome timetable, obtained using state-of-the-art capillary electrophoresis time-of-flight mass spectrometry, will guide further investigations in nucleotide metabolism-related disorders.
