Mannose-6-phosphate attenuates acute lung injury by competitive release of acid sphingomyelinase from the mannose-6-phosphate receptor in endothelial caveolae.

Background: Platelet-activating factor (PAF)-induced pulmonary endothelial barrier failure is mediated by acid sphingomyelinase (ASM) translocation to caveolae. ASM, however, lacks a transmembrane domain for anchoring inside caveolae. We hypothesized that ASM may anchor to cation-independent mannose-6-phosphate receptor (CI-M6PR) in caveolae from where it can be competitively released by M6P.

Radiation Exposure during Cardiac Interventions in Congenital Heart Defects: A Multicenter German Registry Analysis 2012-2020.

Background:  Interventional cardiac catheterizations have gained major importance in the treatment of congenital heart defects (CHDs). Since patients with CHDs frequently require lifelong medical care and sometimes subsequent invasive treatment, repeated radiation exposure during interventional procedures is a relevant issue concerning potential radiation-related risks. Therefore, a 9-year subanalysis on radiation data during interventional cardiac catheterizations from the German Registry for Cardiac Operations and Interventions in patients with CHDs was performed.

Live-Cell Identification of Inhibitors of the Lipid Transfer Protein CERT Using Nanoluciferase Bioluminescence Resonance Energy Transfer (NanoBRET).

A BRET system is described, in which Nanoluciferase was fused to the lipid transfer protein CERT for efficient energy transfer to a Nile red-labeled ceramide, which is either directly bound to CERT or transported to the adjacent Golgi membrane. Bulk formation of sphingomyelin, a major plasma membrane component in mammals, is dependent on CERT-mediated transfer of its predecessor ceramide. CERT is considered a promising drug target but no direct cell-based methods exist to efficiently identify inhibitors.

Expression of major facilitator superfamily protein in transporters - Δ identifies a drug transporter.

To assess the functional relevance of a putative Major Facilitator Superfamily protein (PF3D7_0210300; 'MFSDT') as a drug transporter, using for orthologous protein expression. Complementary Determining Sequence encoding MFSDT was integrated into the genome of genetically engineered strain MSY8 via homologous recombination, followed by assessing its functional relevance as a drug transporter. The modified strain exhibited plasma membrane localization of MFSDT and characteristics of an Major Facilitator Superfamily transporter, conferring resistance to antifungals, ketoconazole and itraconazole.