Diurnal regulation of sphingolipids in blood

High-Throughput GPCRome Screen of Pollutants Reveals the Activity of Polychlorinated Biphenyls at Melatonin and Sphingosine-1-phosphate Receptors

“…More specific examples are illustrated in select reports that establish PCB activity in cellular processes of circadian rhythm and sphingosine metabolism. These studies show that PCB exposure can alter essential genes regulating circadian rhythm , and the metabolic pathway responsible for producing the S1P ligand. , Interestingly, the studies link their findings to similar outcomes regarding PCB toxicity, notably the dysregulation of endothelial cell junctions from PCB exposure. , The interrelationship of these activities is further supported by emerging reports that demonstrate crosstalk between melatonin and S1P signaling pathways, with implications at the receptor level. , Collectively, these independent studies suggest that the activities from PCB95 and PCB52 at MTNR1B and S1PR4 reported here could be essential components in a broader mechanism underlying PCB toxicity. Future investigations into the biological activity of PCBs that consider the melatonin and sphingosine receptors could lead to more impactful discoveries.…”

“…62,64 The interrelationship of these activities is further supported by emerging reports that demonstrate crosstalk between melatonin and S1P signaling pathways, with implications at the receptor level. 65,66 Collectively, these independent studies suggest that the activities from PCB95 and PCB52 at MTNR1B and S1PR4 reported here could be essential components in a broader mechanism underlying PCB toxicity. Future investigations into the biological activity of PCBs that consider the melatonin and sphingosine receptors could lead to more impactful discoveries.…”

Melatonin effect on platelets and coagulation: Implications for a prophylactic indication in COVID-19

“…These changes were not detectable in melatonin receptor-1/2 double knockout mice (MT1/2-/-) and melatonin deficient C57BL/6J mice. However, it is essential to note that no diurnal variation was present in sphingolipid-binding proteins or intraplatelet sphingolipid sources [67] .…”

Sirtuins, Mitochondria and the Melatonergic Pathway in Alzheimer&rsquo;s Disease<strong> </strong>

“…As butyrate converts ceramide to glucosylceramide, the decreased butyrate levels in AD will contribute to heightened ceramide effects on mitochondria, including in immune and glial cells as well as such mitochondrial effects underpinning the suppression of circadian melatonin and orexin [7]. Interestingly, there is a circadian variation in platelets, which may be predominantly determined by pineal melatonin [140], with the inhibition of pineal melatonin occurring prior to dysregulation in wider sleep parameters in mild/moderate AD patients [141]. Notably, PDC disinhibition significant attenuates platelet activation by known activators [142].…”