Anti-ASAH1 monoclonal antibody, clone 2B8

Sphingosine-1-phosphate signaling is emerging as a critical regulator of cellular processes that is initiated by the intracellular production of bioactive lipid molecule, sphingosine-1-phosphate. Binding of sphingosine-1-phosphate to its extracellular receptors activates diverse downstream signaling that play a critical role in governing physiological processes. Increasing evidence suggests that this signaling pathway often gets impaired during pathophysiological and diseased conditions and hence manipulation of this signaling pathway may be beneficial in providing treatment. In this review, we summarized the recent findings of S1P signaling pathway and the versatile role of the participating candidates in context with several disease conditions. Finally, we discussed its possible role as a novel drug target in different diseases.

In the last decade, potential exposure of humans and animals to industrial chemicals and pesticides has been a growing concern. In the present study, di-(2-ethylhexyl) phthalate (DEHP) and mono-(2-ethylhexyl) phthalate (MEHP) were used to model the effects of endocrine-disrupting compounds and their risk in relation to early embryonic losses. Exposure of cumulus oocyte complexes during maturation to 50 mu M MEHP reduced the proportion of oocytes that underwent nuclear maturation (p < 0.05) and increased the proportion of apoptotic oocytes (p < 0.05). Furthermore, phthalates reduced cleavage rate in the MEHP-treated group (p < 0.05) and the proportion of embryos developing to the blastocyst stage in both DEHP- and MEHP-treated groups (p < 0.05). The total cell count for blastocysts developing from MEHP-treated oocytes was lower than in controls (p < 0.05). Exposure of oocytes to MEHP during maturation reduced (p < 0.05) the expression of ASAH1 (an anti-apoptotic factor), CCNA2 (involved in cell cycle control), and POU5F1 (responsible for pluripotency) in matured oocytes. Furthermore, the reduced mRNA expression of POU5F1 and ASAH1 lasted into two-cell stage embryos (p < 0.05). Phthalate-induced alterations in POU5F1, ASAH1, and CCNA2 expression might explain in part the reduced developmental competence of MEHP-treated oocytes.