Untargeted Lipidomics Highlight the Depletion of Deoxyceramides during Therapy‐Induced Senescence
Untargeted Lipidomics Highlight the Depletion of Deoxyceramides during Therapy‐Induced Senescence
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非靶向脂质组学强调治疗过程中脱氧神经酰胺的消耗——诱导衰老
DOI：
10.1002/pmic.202000013
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发表时间：
2020
期刊：
影响因子：
3.4
通讯作者：
Atilla‐Gokcumen, Gunes Ekin
中科院分区：
文献类型：
--
作者：
Millner, Alec;Lizardo, Darleny Y.;Atilla‐Gokcumen, Gunes Ekin
治疗诱导的衰老是细胞周期停滞的状态，其作为对各种化疗试剂的响应而发生，特别是引起DNA损伤的那些。衰老细胞表现出对细胞死亡的抵抗力，并可能损害化疗策略的功效。由于脂质可以表现出促生存活性，因此在本文中设想，探测脂质组可以提供对参与衰老的新型脂质的见解。因此，建立了组织培养模型系统，并对衰老和增殖细胞的细胞脂质体进行了比较分析。在检测到的数千个特征中，确定了17个物种在衰老细胞中显示出显著变化。这些物质中的大多数（17种中的11种）是非典型鞘脂，1-脱氧神经酰胺/二氢神经酰胺，其是在鞘脂生物合成过程中利用丙氨酸而不是丝氨酸产生的。这些脂质在衰老细胞中耗尽。通过向生长培养基中补充代谢前体或直接添加脱氧神经酰胺来提高脱氧神经酰胺的水平，可减少衰老，这表明这些物种可能在此过程中发挥关键作用。
Therapy‐induced senescence is a state of cell cycle arrest that occurs as a response to various chemotherapeutic reagents, especially ones that cause DNA damage. Senescent cells display resistance to cell death and can impair the efficacy of chemotherapeutic strategies. Since lipids can exhibit pro‐survival activity, it is envisioned in this article that probing the lipidome could provide insights into novel lipids that are involved in senescence. Therefore, a tissue culture model system is established and the cellular lipidomes of senescent and proliferating cells are comparatively analyzed. Out of thousands of features detected, 17 species are identified that show significant changes in senescent cells. The majority of these species (11 out of 17) are atypical sphingolipids, 1‐deoxyceramides/dihydroceramides, which are produced as a result of the utilization of alanine, instead of serine during sphingolipid biosynthesis. These lipids are depleted in senescent cells. Elevating the levels of deoxyceramides by supplementing the growth medium with metabolic precursors or by directly adding deoxyceramide result in decreased senescence, suggesting that these species might play a key role in this process.
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影响因子：
18.2
作者：
Campisi J
通讯作者：
Campisi J
影响因子：
8
作者：
Rebbaa, A;Zheng, X;Mirkin, BL
通讯作者：
Mirkin, BL
影响因子：
3.5
作者：
Hammad SM;Baker NL;El Abiad JM;Spassieva SD;Pierce JS;Rembiesa B;Bielawski J;Lopes-Virella MF;Klein RL;DCCT/EDIC Group of Investigators
通讯作者：
DCCT/EDIC Group of Investigators
DOI：
10.1126/science.aar5551
发表时间：
2019-10-18
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Cartier A;Hla T
通讯作者：
Hla T
影响因子：
28.2
作者：
Demaria M;O'Leary MN;Chang J;Shao L;Liu S;Alimirah F;Koenig K;Le C;Mitin N;Deal AM;Alston S;Academia EC;Kilmarx S;Valdovinos A;Wang B;de Bruin A;Kennedy BK;Melov S;Zhou D;Sharpless NE;Muss H;Campisi J
通讯作者：
Campisi J