Oleic acid-induced Ca2+ mobilization in human platelets: Is oleic acid an intracellular messenger?

The purpose of this study was to explore the effect of oleic acid (OA) on intracellular Ca2+ mobilization in human platelets. When applied extracellularly, OA produced a concentration dependent rise in cytosolic [Ca2+] ([Ca2+](cyt)) when extracellular [Ca2+] ([Ca2+](ext) was zero (presence of EGTA), suggesting that OA caused an intracellular release of Ca2+. Intracellular Ca2+ release was directly proportional to entry of OA into platelets and OA entry was indirectly proportional to [Ca2+](ext). In permeabilized platelets, OA caused the release of 45Ca2+ from ATP dependent intracellular stores. Finally, our results show that thrombin stimulated the release of [3H]OA from platelet phospholipids. The saturated fatty acids stearic and palmitic acid did not stimulate an increase in [Ca2+](cyt) under these conditions, but the unsaturated fatty acid, linolenic acid produced effects similar to those of OA, suggesting specificity among fatty acids for effects on [Ca2+](cyt). Taken together, our experiments suggest that OA which has been incorporated into platelet phospholipids was released into the cytosol by thrombin stimulation. Our experiments also show that OA stimulates Ca2+ release from intracellular stores. These results support the hypothesis that OA may serve as an intracellular messenger in human platelets

Effects of suramin on human platelet aggregation and Ca2+ mobilization induced by thrombin and other agonists

The purpose of this study was to investigate the effect of suramin, a polyanionic napthalene sulfonic acid, on human platelet aggregation and Ca2+ mobilization induced by various agonists. Our results show that suramin completely inhibited aggregation by thrombin, platelet activating factor (PAF), alkyllysophosphatidic acid (ALPA), or arachidonic acid in a concentration-dependent manner. The IC50 values of suramin for inhibition of aggregation by PAF, arachidonic acid, and thrombin were 76.7, 239, and 1.49 μg/ml, respectively. Ca2+ mobilization induced by thrombin was inhibited by suramin with an approximate IC50 value of 20 μg/ml. This concentration of suramin had no effect on PAF or oleic acid-induced Ca2+ mobilization. The mechanism by which suramin inhibits aggregation is not clear, but our results suggest that suramin inhibits the ligand-receptor interaction

Defining the genotypic and phenotypic spectrum of X-linked MSL3-related disorder.

Purpose We sought to delineate the genotypic and phenotypic spectrum of female and male individuals with X-linked, MSL3-related disorder (Basilicata-Akhtar syndrome). Methods Twenty-five individuals (15 males, 10 females) with causative variants in MSL3 were ascertained through exome or genome sequencing at ten different sequencing centers. Results We identified multiple variant types in MSL3 (ten nonsense, six frameshift, four splice site, three missense, one in-frame-deletion, one multi-exon deletion), most proven to be de novo, and clustering in the terminal eight exons suggesting that truncating variants in the first five exons might be compensated by an alternative MSL3 transcript. Three-dimensional modeling of missense and splice variants indicated that these have a deleterious effect. The main clinical findings comprised developmental delay and intellectual disability ranging from mild to severe. Autism spectrum disorder, muscle tone abnormalities, and macrocephaly were common as well as hearing impairment and gastrointestinal problems. Hypoplasia of the cerebellar vermis emerged as a consistent magnetic resonance image (MRI) finding. Females and males were equally affected. Using facial analysis technology, a recognizable facial gestalt was determined. Conclusion Our aggregated data illustrate the genotypic and phenotypic spectrum of X-linked, MSL3-related disorder (Basilicata-Akhtar syndrome). Our cohort improves the understanding of disease related morbidity and allows us to propose detailed surveillance guidelines for affected individuals