Thus, pharmacological inhibition of BLT1 may ultimately hold clinical promise, but early intervention may be critical. (C) 2009 Elsevier Ireland Ltd. All rights reserved.”
“Background: Sphingolipids represent a major class of lipids which both serve as structural components of membranes and as bioactive molecules involved in lipid signaling. Ceramide synthases (cers) reside in the center of sphingolipid metabolism by producing ceramide through de novo synthesis or degradative pathways. While the six mammalian

cers family members have been extensively studied in cell culture and in adult tissues, a systematic analysis GSK690693 of cers expression and function during embryogenesis is still lacking. Results: Using bioinformatic and phylogenetic analysis, we identified nine highly find more conserved homologs of the vertebrate cers gene family in the zebrafish genome. A systematic expression analysis throughout five developmental stages indicates that, whereas until 48 hours post fertilization most zebrafish cers homologs are expressed in distinct patterns, e.g., in the intermediate cell mass and the pronephric duct, they show a highly overlapping expression during later stages of embryonic development, mostprominently in the developing brain. Conclusions: In this study, the expression of the cers gene homologs is comprehensively analyzed for the first time during vertebrate embryogenesis. Our data indicate that

each embryonic tissue has a unique profile of cers expression during zebrafish embryogenesis suggesting tissue-specific profiles of ceramides and GSK923295 concentration their derivatives.

Developmental Dynamics 242:189200, 2013. (c) 2012 Wiley Periodicals, Inc.”
“Neuropathies of the peripheral and autonomic nervous systems affect up to half of all people with diabetes, and are major risk factors for foot ulceration and amputation. The aetiology is multifactorial: metabolic changes in diabetes may directly affect neural tissue, but importantly, neurodegenerative changes are precipitated by compromised nerve vascular supply. Experiments in animal models of diabetic neuropathy suggest that similar metabolic sequelae affect neurons and vasa nervorum endothelium. These include elevated polyol pathway activity, oxidative stress, the formation of advanced glycation and Iipoxidation end products, and various pro-inflammatory changes such as elevated protein kinase C, nuclear factor kappa B and p38 mitogen activated protein kinase signalling. These mechanisms do not work in isolation but strongly interact in a mutually facilitatory fashion. Nitrosative stress and the induction of the enzyme poly (ADP-ribose) polymerase form one important link between physiological stressors such as reactive oxygen species and the pro-inflammatory mechanisms. Recently, evidence points to endoplasmic stress and the unfolded protein response as forming another crucial link.