The sphingolipid backbone ceramide (Cer) is a major component of lipid lamellae in the stratum corneum of epidermis and has a pivotal role in epidermal barrier formation. Unlike Cers in other tissues, Cers in epidermis contain extremely long fatty acids (FAs). Decreases in epidermal Cer levels, as well as changes in their FA chain lengths, cause several cutaneous disorders. However, the molecular mechanisms that produce such extremely long Cers and determine their chain lengths are poorly understood. We generated mice deficient in the Elovl1 gene, which encodes the FA elongase responsible for producing C 20 to C 28 FAs. Elovl1 knockout mice died shortly after birth due to epidermal barrier defects. The lipid lamellae in the stratum corneum were largely diminished in these mice. In the epidermis of the Elovl1-null mice, the levels of Cers with >C 26 FAs were decreased, while those of Cers with
Ceramide and complex sphingolipids regulate important cellular functions including cell growth, apoptosis, and signaling. Dysregulation of sphingolipid metabolism leads to pathological consequences such as sphingolipidoses and insulin resistance. Ceramides in mammals vary greatly in their acyl-chain composition: six different ceramide synthase isozymes (CERS1-6) that exhibit distinct substrate specificity and tissue distribution account for this diversity. In the present study, we demonstrated that CERS2-6 were phosphorylated at the cytoplasmic C-terminal regions. Most of the phosphorylated residues conformed to a consensus motif for phosphorylation by casein kinase 2 (CK2), and treatment of cells with the CK2-specific inhibitor CX-4945 lowered the phosphorylation levels of CERS2, -4, -5, and -6. Phosphorylation of CERS2 was especially important for its catalytic activity, acting mainly by increasing its V max value. Phosphorylation modestly increased the catalytic activities of CERS4 and -5 and mildly increased those of CERS3 and -6. Dephosphorylation of endogenous ceramide synthases in the mouse brain led to severely reduced activity toward the Cers2 substrates C22:0/C24:0-CoAs and modestly reduced activity toward the Cers5/6 substrate C16:0-CoA. These results suggest that the phosphorylation of ceramide synthases may be a key regulatory point in the control of the distribution and levels of sphingolipids of various acyl-chain lengths.Sphingolipids, one of the major lipid constituents of eukaryotic membranes, mediate a number of cellular and physiological functions such as cell growth, apoptosis, immune responses, and the epidermal permeability barrier, whereas their abnormal metabolism is involved in diseases such as sphingolipidoses, neural disorders, and diabetes (1-7). Ceramides are located in the hub of sphingolipid metabolism. Ceramides are precursors for complex sphingolipids, whereas their hydrolysis releases a sphingoid long-chain base and a fatty acid (FA).2 The released long-chain base can then be recycled to synthesize new ceramide, or metabolized further into other lipids such as sphingosine 1-phosphate (8 -10). Ceramide synthases catalyze the formation of an amide bond between the long-chain base and the FA in the endoplasmic reticulum. In most tissues, the chain lengths of the FA moieties of ceramides are C16 -
Trigger wrist is a rare condition unlike the trigger finger of the metacarpophalangeal joint. This report describes a case of trigger wrist secondary to a giant cell tumour of the flexor tendon sheath. No previous reports are available in the medical literature.
Ten millimeter gaps in sciatic nerves of rats were repaired by vein grafting (n = 30) and by nerve grafting (n = 30). Electrophysiologic evaluation demonstrated that the nerve-graft group had a significantly higher percentage of re-innervation and shorter delay of terminal latency in myoelectrical response evoked by electrical stimulation of the sciatic nerve, compared with the vein-graft group at two and three months. But there were no differences between the two grafted groups after six months. In both grafted groups, the numbers of myelinated nerve fibers increased substantially over time, although the vein-grafted segments had smaller numbers of fibers than the nerve-grafted segments at both three and 12 months. Microangiograms also demonstrated different patterns of revascularization between the two groups. Results suggest that, although autologous vein grafting requires a longer period of time for nerve regeneration, compared with autologous nerve grafting, its ability to repair nerve is considerable.
Competitive blood flow reduces internal thoracic artery graft flow and diameter according to the grade of the native coronary artery stenosis. These data suggest that grafting the internal thoracic artery to the coronary artery with stenosis of a low grade can cause graft atrophy and failure.
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