Sphingolipid metabolism regulates development and lifespan in Caenorhabditis elegans.
Sphingolipid metabolism regulates development and lifespan in Caenorhabditis elegans.
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DOI：
10.1016/j.mad.2014.11.002
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发表时间：
2014-12-15
影响因子：
5.3
通讯作者：
Mattson, Mark P.
中科院分区：
文献类型：
--
作者：
Cutler, Roy G.;Thompson, Kenneth W.;Camandola, Simonetta;Mack, Kendra T.;Mattson, Mark P.
鞘脂是参与形成脂质筏结构域的细胞膜的高度保守的脂质组分，脂质筏结构域容纳参与调节细胞分裂、成熟和终末分化的许多受体和细胞间信号传导因子。通过在秀丽隐杆线虫中使用药理学和遗传学工具测量和操纵鞘脂代谢，我们提供了特定神经酰胺（例如，DC 18：1-C24：1），神经节苷脂（例如，GM 1-C24：1）和鞘磷脂（例如，dC 18：1-C18：1）影响发育速率和寿命。我们发现，在许多鞘脂物种的脂肪酸链去饱和和延长的水平增加在发展和老化，没有这样的变化，在发育停滞的dauer幼虫或正常成人后，食物撤退（抗衰老干预）。针对丝氨酸棕榈酰转移酶和葡糖神经酰胺合酶的药理学抑制剂和小干扰RNA起到减缓发育速率、延长生殖期和增加寿命的作用。相比之下，蠕虫喂养的蛋黄饮食中富含鞘脂表现出加速发展和缩短寿命。我们的研究结果表明，鞘脂的积累和重塑是决定线虫模型中的发育速率和寿命的关键事件，鞘磷脂的合成及其代谢为神经酰胺和神经节苷脂加速了发育速率和衰老。
Sphingolipids are a highly conserved lipid component of cell membranes involved in the formation of lipid raft domains that house many of the receptors and cell-to-cell signaling factors involved in regulating cell division, maturation, and terminal differentiation. By measuring and manipulating sphingolipid metabolism using pharmacological and genetic tools in Caenorhabditis elegans, we provide evidence that the synthesis and remodeling of specific ceramides (e.g., dC18:1–C24:1), gangliosides (e.g., GM1–C24:1), and sphingomyelins (e.g., dC18:1–C18:1) influence development rate and lifespan. We found that the levels of fatty acid chain desaturation and elongation in many sphingolipid species increased during development and aging, with no such changes in developmentally-arrested dauer larvae or normal adults after food withdrawal (an anti-aging intervention). Pharmacological inhibitors and small interfering RNAs directed against serine palmitoyl transferase and glucosylceramide synthase acted to slow development rate, extend the reproductive period, and increase lifespan. In contrast, worms fed an egg yolk diet rich in sphingolipids exhibited accelerated development and reduced lifespan. Our findings demonstrate that sphingolipid accumulation and remodeling are critical events that determine development rate and lifespan in the nematode model, with both development rate and aging being accelerated by the synthesis of sphingomyelin, and its metabolism to ceramides and gangliosides.
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影响因子：
11.8
作者：
Gerisch, B;Weitzel, C;Antebi, A
通讯作者：
Antebi, A
DOI：
10.1098/rstb.1991.0028
发表时间：
1991-04-29
影响因子：
6.3
作者：
KIRKWOOD, TBL;ROSE, MR
通讯作者：
ROSE, MR
影响因子：
5.3
作者：
Hayashi, H;Kimura, N;Yanagisawa, K
通讯作者：
Yanagisawa, K
影响因子：
4.5
作者：
Huang X;Liu J;Dickson RC
通讯作者：
Dickson RC
影响因子：
4
作者：
Lochnit, G;Bongaarts, R;Geyer, R
通讯作者：
Geyer, R