BACKGROUND: Lipoprotein-associated phospholipase A(2) (Lp-PLA(2)) has been implicated in development of atherosclerosis; however, recent randomized trials of Lp-PLA(2) inhibition reported no beneficial effects on vascular diseases. In East Asians, a loss-of-function variant in the PLA2G7 gene can be used to assess the effects of genetically determined lower Lp-PLA(2) METHODS: PLA2G7 V279F (rs76863441) was genotyped in 91 428 individuals randomly selected from the China Kadoorie Biobank of 0.5 M participants recruited in 2004-08 from 10 regions of China, with 7 years' follow-up. Linear regression was used to assess effects of V279F on baseline traits. Logistic regression was conducted for a range of vascular and non-vascular diseases, including 41 ICD-10 coded disease categories. RESULTS: PLA2G7 V279F frequency was 5% overall (range 3-7% by region), and 9691 (11%) participants had at least one loss-of-function variant. V279F was not associated with baseline blood pressure, adiposity, blood glucose or lung function. V279F was not associated with major vascular events [7141 events; odds ratio (OR) = 0.98 per F variant, 95% confidence interval (CI) 0.90-1.06] or other vascular outcomes, including major coronary events (922 events; 0.96, 0.79-1.18) and stroke (5967 events; 1.00, 0.92-1.09). Individuals with V279F had lower risks of diabetes (7031 events; 0.91, 0.84-0.98) and asthma (182 events; 0.53, 0.28-0.98), but there was no association after adjustment for multiple testing. CONCLUSIONS: Lifelong lower Lp-PLA(2) activity was not associated with major risks of vascular or non-vascular diseases in Chinese adults. Using functional genetic variants in large-scale prospective studies with linkage to a range of health outcomes is a valuable approach to inform drug development and repositioning.
Title: N-butyryl-homoserine lactone, a bacterial quorum-sensing signaling molecule, induces intracellular calcium elevation in Arabidopsis root cells Song S, Jia Z, Xu J, Zhang Z, Bian Z Ref: Biochemical & Biophysical Research Communications, 414:355, 2011 : PubMed
N-acyl-L-homoserine lactones (AHLs) are quorum sensing (QS) signal molecules that are commonly used in gram-negative bacteria. Recently, it has become evident that AHLs can influence the behavior of plant cells. However, little is known about the mechanism of the plants' response to these bacterial signals. Calcium ions (Ca(2+)), ubiquitous intracellular second messengers, play an essential role in numerous signal transduction pathways in plants. In this study, the cytosolic free Ca(2+) concentration ([Ca(2+)](cyt)) was measured by a luminometric method in the excised root cells of Arabidopsis plants that were treated with N-butyryl-homoserine lactone (C4-HSL). There was a transient and immediate increase in [Ca(2+)](cyt) levels, and the highest level (0.4 muM), approximately 2-fold higher than the basal level, was observed at the 6th second after the addition of 10 muM C4-HSL. Pretreatments with La(3+), verapamil or ethylene glycol tetraacetic acid (EGTA) inhibited the increase in [Ca(2+)](cyt) caused by C4-HSL, whereas it remained unaffected by pretreatment with Li(+), indicating that the Ca(2+) contributing to the increase in [Ca(2+)](cyt) was mobilized from the extracellular medium via the plasma membrane Ca(2+) channels but not from the intracellular Ca(2+) stores. Furthermore, electrophysiological approaches showed that the transmembrane Ca(2+) current was significantly increased with the addition of C4-HSL. Taken together, our observations suggest that C4-HSL may act as an elicitor from bacteria to plants and that Ca(2+) signaling participates in the ability of plant cells to sense the bacterial QS signals.
