resolvin D1(1-)

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 脂肪酰基
• 英文名称: resolvin D1(1-)
• 英文别名: (4Z,7S,8R,9E,11E,13Z,15E,17S,19Z)-7,8,17-trihydroxydocosa-4,9,11,13,15,19-hexaenoate
• 化学式: C22H31O5-
• 分子量: 375.5
• InChiKey: OIWTWACQMDFHJG-CCFUIAGSSA-M

计算性质

• 辛醇/水分配系数(LogP)：
  3.7
• 重原子数：
  27
• 可旋转键数：
  13
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.41
• 拓扑面积：
  101
• 氢给体数：
  3
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  nicotinamide adenine dinucleotide 、 resolvin D1(1-) 生成 8-oxoresolvin D1(1-) 、 氢(+1)阳离子 、 NADH
  参考文献：
  名称：

  Resolvin D1 and Resolvin D2 Govern Local Inflammatory Tone in Obese Fat

  摘要：

  肥胖和与之相关的疾病的普遍发生率的前所未有的增加与脂肪组织中慢性低级别炎症状态有因果关系。及时解决炎症和恢复组织的稳态是减少肥胖引起的代谢功能障碍的关键。在这项研究中，我们研究了在炎症的脂肪组织中Resolvins D1 (RvD1，7S，8R，17S-三羟基-4Z，9E，11E，13Z，15E，19Z-二十二碳六烯酸)和D2 (RvD2，7S，16R，17S-三羟基-4Z，8E，10Z，12E，14E，19Z-二十二碳六烯酸)的生物合成、转化和作用，这是有效的抗炎和促解决的脂质介质（LMs），以及它们调节单核细胞与脂肪细胞相互作用的能力。脂质介质代谢组学从内源性来源中鉴定了人和小鼠脂肪组织中的RvD1和RvD2。我们还在这些组织中鉴定了促解决受体（即ALX/FPR2、ChemR23和GPR32）。与瘦组织相比，肥胖脂肪组织显示出这些内源性抗炎信号的不足。在炎症的肥胖脂肪组织中，RvD1和RvD2分别以时间和浓度依赖的方式挽救了脂肪素的表达和分泌受损，同时减少了前炎症脂肪细胞因子的产生，包括瘦素、TNF-α、IL-6和IL-1β。RvD1和RvD2分别减少了MCP-1和白三烯B4刺激的单核细胞粘附到脂肪细胞和它们的跨脂肪迁移。脂肪组织迅速将两种解决方案（Rvs）转化为新的氧化-Rvs。RvD2被酶促转化为7-氧化-RvD2，作为其保留脂肪定向RvD2作用的主要代谢途径。这些结果表明，在脂肪组织中，D系列Rvs（RvD1和RvD2）是有效的促解决介质，可以抵消肥胖引起的脂肪细胞因子产生和单核细胞在炎症诱导的肥胖脂肪组织中的积累。

  DOI：

  10.4049/jimmunol.1201272

文献信息

• Resolvin D1 and Its Aspirin-triggered 17R Epimer
  作者：Yee-Ping Sun、Sungwhan F. Oh、Jasim Uddin、Rong Yang、Katherine Gotlinger、Eric Campbell、Sean P. Colgan、Nicos A. Petasis、Charles N. Serhan

  DOI：10.1074/jbc.m609212200

  日期：2007.3

  We recently uncovered two new families of potent docosahexaenoic acid-derived mediators, termed D series resolvins (Rv; resolution phase interaction products) and protectins. Here, we assign the stereochemistry of the conjugated double bonds and chirality of alcohols present in resolvin D1 (RvD1) and its aspirin-triggered 17R epimer (AT-RvDl) with compounds prepared by total organic synthesis. In addition, docosahexaenoic acid was converted by a single lipoxygenase in a "one-pot" reaction to RvD1 in vitro. The synthetic compounds matched the physical and biological properties of those enzymatically generated. RvD1 proved to be 7S,8R,17S-trihydroxy4Z,9E,11E,13Z,15E,19Z-docosahexaenoic acid, AT-RvD1 matched 7S,8R,17R-trihydroxy-4Z,9E,11E,13Z,15E,19Z-docosahexaenoic acid, and they both stopped transendothelial migration of human neutrophils (EC50 similar to 30 nm). In murine peritonitis in vivo, RvD1 and AT-RvD1 proved equipotent (at nanogram dosages), limiting polymorphonuclear leukocyte infiltration in a dose-dependent fashion. RvD1 was converted by eicosanoid oxidoreductase to novel 8-oxo- and 17-oxo-RvD1 that gave dramatically reduced bioactivity, whereas enzymatic conversion of AT-RvD1 was sharply reduced. These results establish the complete stereochemistry and actions of RvD1 and AT-RvDl as well as demonstrate the stereoselective basis for their enzymatic inactivation. RvD1 regulates human polymorphonuclear leukocyte transendothelial migration and is antiinflammatory. When its carbon 17S alcohol is enzymatically converted to 17-oxo-RvD1, it is essentially inactive, whereas the 17R alcohol configuration in its aspirin-triggered form (ATRvD1) resists rapid inactivation. These results maycontribute to the beneficial actions of aspirin and omega-3 fish oils in humans.
• Resolvin D1 and Resolvin D2 Govern Local Inflammatory Tone in Obese Fat
  作者：Joan Clària、Jesmond Dalli、Stephanie Yacoubian、Fei Gao、Charles N. Serhan

  DOI：10.4049/jimmunol.1201272

  日期：2012.9.1

  The unprecedented increase in the prevalence of obesity and obesity-related disorders is causally linked to a chronic state of low-grade inflammation in adipose tissue. Timely resolution of inflammation and return of this tissue to homeostasis are key to reducing obesity-induced metabolic dysfunctions. In this study, with inflamed adipose, we investigated the biosynthesis, conversion, and actions of Resolvins D1 (RvD1, 7S,8R,17S-trihydroxy-4Z,9E,11E,13Z,15E,19Z-docosahexaenoic acid) and D2 (RvD2, 7S,16R,17S-trihydroxy-4Z,8E,10Z,12E,14E,19Z-docosahexaenoic acid), potent anti-inflammatory and proresolving lipid mediators (LMs), and their ability to regulate monocyte interactions with adipocytes. Lipid mediator-metabololipidomics identified RvD1 and RvD2 from endogenous sources in human and mouse adipose tissues. We also identified proresolving receptors (i.e., ALX/FPR2, ChemR23, and GPR32) in these tissues. Compared with lean tissue, obese adipose showed a deficit of these endogenous anti-inflammatory signals. With inflamed obese adipose tissue, RvD1 and RvD2 each rescued impaired expression and secretion of adiponectin in a time- and concentration-dependent manner as well as decreasing proinflammatory adipokine production including leptin, TNF-α, IL-6, and IL-1β. RvD1 and RvD2 each reduced MCP-1 and leukotriene B4-stimulated monocyte adhesion to adipocytes and their transadipose migration. Adipose tissue rapidly converted both resolvins (Rvs) to novel oxo-Rvs. RvD2 was enzymatically converted to 7-oxo-RvD2 as its major metabolic route that retained adipose-directed RvD2 actions. These results indicate, in adipose, D-series Rvs (RvD1 and RvD2) are potent proresolving mediators that counteract both local adipokine production and monocyte accumulation in obesity-induced adipose inflammation.

  肥胖和与之相关的疾病的普遍发生率的前所未有的增加与脂肪组织中慢性低级别炎症状态有因果关系。及时解决炎症和恢复组织的稳态是减少肥胖引起的代谢功能障碍的关键。在这项研究中，我们研究了在炎症的脂肪组织中Resolvins D1 (RvD1，7S，8R，17S-三羟基-4Z，9E，11E，13Z，15E，19Z-二十二碳六烯酸)和D2 (RvD2，7S，16R，17S-三羟基-4Z，8E，10Z，12E，14E，19Z-二十二碳六烯酸)的生物合成、转化和作用，这是有效的抗炎和促解决的脂质介质（LMs），以及它们调节单核细胞与脂肪细胞相互作用的能力。脂质介质代谢组学从内源性来源中鉴定了人和小鼠脂肪组织中的RvD1和RvD2。我们还在这些组织中鉴定了促解决受体（即ALX/FPR2、ChemR23和GPR32）。与瘦组织相比，肥胖脂肪组织显示出这些内源性抗炎信号的不足。在炎症的肥胖脂肪组织中，RvD1和RvD2分别以时间和浓度依赖的方式挽救了脂肪素的表达和分泌受损，同时减少了前炎症脂肪细胞因子的产生，包括瘦素、TNF-α、IL-6和IL-1β。RvD1和RvD2分别减少了MCP-1和白三烯B4刺激的单核细胞粘附到脂肪细胞和它们的跨脂肪迁移。脂肪组织迅速将两种解决方案（Rvs）转化为新的氧化-Rvs。RvD2被酶促转化为7-氧化-RvD2，作为其保留脂肪定向RvD2作用的主要代谢途径。这些结果表明，在脂肪组织中，D系列Rvs（RvD1和RvD2）是有效的促解决介质，可以抵消肥胖引起的脂肪细胞因子产生和单核细胞在炎症诱导的肥胖脂肪组织中的积累。