HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text (PDF) All Versions of this Article: 297/6/E1276    most recent ajpendo.00475.2009v1 Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Cheng, L. Articles by Shi, Y. PubMed PubMed Citation Articles by Cheng, L. Articles by Shi, Y.

RESEARCH ARTICLE

A Regulatory Role of LPCAT1 in the Synthesis of Inflammatory Lipids, PAF and LPC, in the Retina of Diabetic Mice

¹Cellular and Molecular Physiology, Pennsylvania State University College of Medicine ²Key Laboratory of Human Functional Genomics, Nanjing Medical University ³Cellular and Molecular Physiology, Pennsylvania State University College of Medicine, 500 University Drive, Hershey, Pennsylvania, 17033, United States

Submitted 30 July 2009 ; revised 15 September 2009 ; accepted in final form 21 September 2009

Platelet activation factor (PAF) and lysophosphotidylcholine (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 anti-inflammatory response by converting LPC to PC. Intriguingly, the LPCAT1 enzyme also catalyzes the synthesis of PAF from lyso-PAF using 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 LPCAT1 plays an important role in the inactivation of PAF by catalyzing the synthesis of alkyl-PC, an inactivated form of PAF, using 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 retina. Moreover, the LPCAT1 mRNA levels and acyltransferase activity towards lyso-PAF and LPC were significantly down-regulated in retina and brain tissues in responses to the onset of diabetes in Ins2^Akita and db/db mice, a mouse model of type 1 and type 2 diabetes, respectively. Conversely, treatment of db/db mice with rosiglitazone, an antidiabetic compound, significantly up-regulated the LPCAT1 mRNA levels concurrent with increased acyltransferase activity in 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.

Diabetic retinopathy; platelet-activating factor