A regulatory role of LPCAT1 in the synthesis of inflammatory lipids, PAF and LPC, in the retina of diabetic mice
A regulatory role of LPCAT1 in the synthesis of inflammatory lipids, PAF and LPC, in the retina of diabetic mice
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DOI：
10.1152/ajpendo.00475.2009
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发表时间：
2009-12-01
影响因子：
5.1
通讯作者：
Shi, Yuguang
中科院分区：
文献类型：
--
作者：
Cheng, Long;Han, Xiao;Shi, Yuguang
郑丽，韩X，施Y. LPCAT 1在糖尿病小鼠视网膜炎性脂质PAF和LPC合成中的调节作用Am J Physiol Endocrinol Metab 297：E1276-E1282，2009.首次发表于2009年9月22日; doi：10.1152/ajpendo.00475.2009. -血小板活化因子（PAF）和溶血磷脂酰胆碱（LPC）是有效的炎症脂质。PAF和LPC水平升高与糖尿病视网膜病变和神经变性的发生相关。然而，这些缺陷背后的分子机制仍然难以捉摸。LPCAT 1是新近报道的一种溶血磷脂酰基转移酶，通过其在LPC转化为PC中的作用而参与抗炎反应。有趣的是，LPCAT 1酶也催化PAF的合成从溶血PAF使用乙酰辅酶A作为底物。目前的研究调查了LPCAT 1在糖尿病发病过程中炎症脂质合成中的调节作用。我们的工作表明，LPCAT 1通过催化烷基-PC的合成在PAF的失活中起重要作用，烷基-PC是PAF的失活形式，其使用酰基-CoA和溶血-PAF作为底物。为了支持LPCAT 1在糖尿病视网膜病变的抗炎反应中的作用，LPCAT 1在视网膜中表达最丰富。此外，在1型和2型糖尿病的小鼠模型Ins2（秋田）和db/db小鼠中，视网膜和脑组织中的LPCAT 1 mRNA水平和对lyso-PAF和LPC的酰基转移酶活性分别响应于糖尿病的发作而显著下调。相反，用罗格列酮（一种抗糖尿病化合物）治疗db/db小鼠，可显著上调LPCAT 1 mRNA水平，同时增加视网膜和大脑中的酰基转移酶活性。总的来说，这些发现确定了LPCAT 1在催化糖尿病小鼠视网膜中炎性脂质失活中的新的调节作用。
Cheng L, Han X, Shi Y. A regulatory role of LPCAT1 in the synthesis of inflammatory lipids, PAF and LPC, in the retina of diabetic mice. Am J Physiol Endocrinol Metab 297: E1276-E1282, 2009. First published September 22, 2009; doi:10.1152/ajpendo.00475.2009.-Platelet-activating factor (PAF) and lysophosphatidylcholine (LPC) are potent inflammatory lipids. Elevated levels of PAF and LPC are associated with the onset of diabetic retinopathy and neurodegeneration. However, the molecular mechanisms underlying such defects remain elusive. LPCAT1 is a newly reported lysophospholipid acyltransferase implicated in the anti-inflammatory response by its role in conversion of LPC to PC. Intriguingly, the LPCAT1 enzyme also catalyzes the synthesis of PAF from lyso-PAF with use of acetyl-CoA as a substrate. The present studies investigated regulatory roles of LPCAT1 in the synthesis of inflammatory lipids during the onset of diabetes. Our work shows that LPCAT1 plays an important role in the inactivation of PAF by catalyzing the synthesis of alkyl-PC, an inactivated form of PAF with use of acyl-CoA and lyso-PAF as substrates. In support of a role of LPCAT1 in anti-inflammatory responses in diabetic retinopathy, LPCAT1 is most abundantly expressed in the retina. Moreover, LPCAT1 mRNA levels and acyltransferase activity toward lyso-PAF and LPC were significantly downregulated in retina and brain tissues in response to the onset of diabetes in Ins2(Akita) and db/db mice, mouse models of type 1 and type 2 diabetes, respectively. Conversely, treatment of db/db mice with rosiglitazone, an antidiabetes compound, significantly upregulated LPCAT1 mRNA levels concurrently with increased acyltransferase activity in the retina and brain. Collectively, these findings identified a novel regulatory role of LPCAT1 in catalyzing the inactivation of inflammatory lipids in the retina of diabetic mice.