ABSTRACT
Hydroxyeicosatetraenoic acids (HETEs) are metabolites of arachidonate acid (AA) oxidized by lipoxygenases or cytochrome P450 enzymes (CYP450). Since lipoxygenases and CYP450 enzymes widely exist in different organs and tissues, HETEs play significant roles in normal physiological and pathophysiological conditions. Mounting evidence has shown that HETEs play roles in modulation of inflammation during diabetes development. And accumulating evidence suggests that in prediabetic conditions, HETEs have already impacted on adipose tissue, kidney, heart, and islet. In the current review, we focused on the role of specific HETEs, namely 5-HETE, 12-HETE, 15-HETE and 20-HETE in diabetes, and highlighted their effects in the development of diabetes and diabetes-related complications. In conclusion, elucidation of HETEs' impacts on different organs that contribute to the development of diabetes leads to identification of novel therapeutic modalities.
Subject(s)
Diabetes Mellitus , Hydroxyeicosatetraenoic Acids , Humans , Cytochrome P-450 Enzyme System/metabolism , Arachidonic Acids , LipoxygenasesABSTRACT
Intracellular platelet activating-factor acetylhydrolase type II (PAF-AH II) is a 40-kDa monomeric enzyme. It was originally identified as an enzyme that hydrolyzes the acetyl group of PAF (1-O-alkyl-2-acetyl-sn-glycero-3-phosphocholine). As a member of phospholipase A2 super family, PAF-AH II has broad substrate specificity. It can hydrolyze phospholipids with relatively short-length or oxidatively modified sn-2 chains which endows it with various functions such as protection against oxidative stress, transacetylase activity and producing lipid mediators. PAF-AH II has been proven to be involved in several diseases such as allergic diseases, oxidative stress-induced injury and ischemia injury, thus it has drawn more attention from researchers. In this paper, we outline an entire summary of PAF-AH II, including its structure, substrate specificity, activity assay, inhibitors and biological activities.