Expression of bioactive lysophospholipids and processing enzymes in the vitreous from patients with proliferative diabetic retinopathy

Abstract

BackgroundThe bioactive lysophospholipids phosphatidic acid (PA), lysophosphatidic acid (LPA) and sphingosine-1-phosphate (S1P) have been implicated in mediating cell migration, proliferation and apoptosis, inflammation, angiogenesis and fibrosis. This study was conducted to measure the levels of PA, LPA, LPA-producing enzymes phospholipase A1/A2 (PLA1A/PLA2, respectively) and acylgylycerol kinase (AGK), the S1P receptor S1PR1, the S1P catabolising enzyme S1P lyase (SPL) and 5-lipoxygenase in the vitreous fluid from patients with proliferative diabetic retinopathy (PDR). In addition, we investigated the correlations between the levels of PA and LPA and the levels of the inflammatory and endothelial dysfunction biomarker soluble vascular cell adhesion molecule-1 (sVCAM-1).MethodsVitreous samples from 34 PDR and 29 nondiabetic patients were studied by biochemical and enzyme-linked immunosorbent assays and Western blot analysis.ResultsPA, LPA and sVCAM-1 levels in vitreous samples from PDR patients were significantly higher than those in nondiabetic patients. Significant correlations were observed between levels of LPA and levels of PA and sVCAM-1. Western blot analysis revealed a significant increase in the expression of PLA1A, AGK, S1PR1 and SPL in vitreous samples from PDR patients compared to nondiabetic controls, whereas PLA2 and 5-lipoxygenase were not detected.ConclusionsOur findings suggest that the enzymatic activities of PLA1A and AGK might be responsible for increased synthesis of LPA in PDR and that PLA1A, but not PLA2 is responsible for deacylation of PA to generate LPA. S1PR1 and SPL might regulate inflammatory, angiogenic and fibrogenic responses in PDR.

Lysophospholipid Receptors, as Novel Conditional Danger Receptors and Homeostatic Receptors Modulate Inflammation—Novel Paradigm and Therapeutic Potential

“…As illustrated in Table 2A, endogenous LPLs were upregulated in the presence of metabolic and inflammatory disorders such as type 2 diabetes, diabetic retinopathy, acute coronary syndrome and autoimmune disorders. High serum levels of S1P, LPA and LPI was observed in patients with juvenile-onset systemic lupus erythematosus [47], proliferative diabetic retinopathy [48] and obese type 2 diabetes [49] respectively. Interestingly, acute coronary syndrome increased a bunch of pro-inflammatory LPLs (LPA, LPG, LPI and LPC) and anti-inflammatory LPLs (LysoPS and LPE).…”

LC‐MS based metabolomics identification of novel biomarkers of tobacco smoke‐induced chronic bronchitis

“…Lysophosphatides (LPLs) include lysophosphatidylcholine (LPC), LPE and LPA, which are converted from PLs through the hydrolysis by the enzyme of phospholipase A 2 (PLA 2 ) (Schober et al, 2009). According to previous research, it is generally recognized that the level of LPL increases under inflammatory conditions such as diabetes (Abu El-Asrar et al, 2014), liver disease (Maricic et al, 2014) and asthma (Knowlden and Georas, 2014). Inflammation is characterized by the infiltration of cells, particularly neutrophilic granulocytes, and the release of PLA 2 , which leads to an increase in the concentration of LPLs.…”

A facile stable-isotope dilution method for determination of sphingosine phosphate lyase activity

“…For example, the aldehyde product of the reaction catalyzed by SPL may contribute to manifestations of Sjogren-Larsson syndrome, a disease caused by mutations in FALDH that result in accumulation of fatty aldehydes (Nakahara et al, 2012). Alterations in SPL gene and protein expression have been observed in other disease states (Abu El-Asrar et al, 2014; Brizuela:2012ew; Ceccom et al, 2014; Oskouian et al, 2006; Testai et al, 2015). However, thus far no SPL mutation has been shown to play a direct role in the pathophysiology of a human disease.…”