Inhibitory Effect of Orientin on Secretory Group IIA Phospholipase A 2
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Inhibitory Effect of Orientin on Secretory Group IIA Phospholipase A2 Jong-Sup Bae1,2
Abstract—It is well known that the expression level of secretory group IIA phospholipase A2 (sPLA2IIA) is elevated in inflammatory diseases and lipopolysaccharide (LPS) upregulates the expression of sPLA2-IIA in human umbilical vein endothelial cells (HUVECs). Orientin, a C-glycosyl flavonoid, is known to have anxiolytic, anti-oxidative, and anti-inflammatory activity. Here, orientin was examined for its effects on the expression and activity of sPLA2-IIA in HUVECs and mouse. Prior treatment of cells or mouse with orientin inhibited LPS-induced expression and activity of sPLA2-IIA. And orientin suppressed the activation of cytosolic phospholipase A2 (cPLA2) and extracellular signal-regulated kinase (ERK) 1/2 by LPS. Therefore, these results suggest that orientin may inhibit LPS-mediated expression of sPLA2-IIA by suppression of cPLA2 and ERK 1/2. KEY WORDS: orientin; HUVEC; sPLA2-IIA; inflammation.
INTRODUCTION There are at least 20 distinct mammalian phospholipases A2 (PLA2) enzymes (of which 18 occur in humans) that catalyze the hydrolysis of the sn-2 ester bond (middle) of a phospholipid to generate a lysophospholipid and a fatty acid such as arachidonic acid (AA) and oleic acid [1–3]. And released fatty acid can be important as the precursor of eicosanoids, which are potent mediators of vascular inflammation and signal transduction [3]. And AA is oxygenated and further transformed into a variety of products which mediate or modulate inflammatory reactions [3]. PLA2 enzymes can be broadly classified into three major classes on the basis of their requirements for calcium, the mechanism of their catalytic action, their molecular weight, and also sequence homology: secretory PLA 2 (sPLA 2 ), cytosolic PLA 2 (cPLA 2 ), Ca 2 + independent PLA2 (iPLA2), and lipoprotein associated PLA2 [1, 2]. The secretory enzymes, sPLA2 groups IB,
1
College of Pharmacy, CMRI, Research Institute of Pharmaceutical Sciences, Kyungpook National University, 80 Daehak-ro, Buk-gu, Daegu, 702-701, Republic of Korea 2 To whom correspondence should be addressed at College of Pharmacy, CMRI, Research Institute of Pharmaceutical Sciences, Kyungpook National University, 80 Daehak-ro, Buk-gu, Daegu, 702-701, Republic of Korea. E-mail: [email protected]
IIA, IID, IIE, IIF, V, X, and XIIA, are all approximately 14 kDa, and all possess a catalytic histidine residue that functions as a general base to activate a water molecule for hydrolysis of the ester bond [1, 2]. sPLA2 group IIA (sPLA 2 -IIA) was implicated early following the observation that large amounts of sPLA2-IIA are present in the synovial fluid of rheumatoid arthritis patients and in platelets in the joint [4, 5]. Additionally, massively elevated levels of sPLA2-IIA were found in the serum of patients with septic shock acute pancreatitis and peritonitis and that sPLA 2 -IIA gene expression is upregulated by inflammatory cytokines and sub-nanomolar levels of bacterial LPS [6–11]. Together, these findin
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