Anti-ACACB (aa 217-231) polyclonal antibody

Lipin-1 deficiency is associated with massive rhabdomyolysis episodes in humans, precipitated by febrile illnesses. Despite well-known roles of lipin-1 in lipid biosynthesis and transcriptional regulation, the pathogenic mechanisms leading to rhabdomyolysis remain unknown. Here we show that primary myoblasts from lipin-1-deficient patients exhibit a dramatic decrease in LPIN1 expression and phosphatidic acid phosphatase 1 activity, and a significant accumulation of lipid droplets (LD). The expression levels of LPIN1-target genes [peroxisome proliferator-activated receptors delta and alpha (PPAR delta, PPAR alpha), peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1 alpha), acyl-coenzyme A dehydrogenase, very long (ACADVL), camitine palmitoyltransferase IB and 2 (CPT1B and CPT2)] were not affected while lipin-2 protein level, a closely related member of the family, was increased. Microarray analysis of patients' myotubes identified 19 down-regulated and 51 up-regulated genes, indicating pleiotropic effects of lipin-1 deficiency. Special attention was paid to the up-regulated ACACB (acetyl-CoA carboxylase beta), a key enzyme in the fatty acid synthesis/oxidation balance. We demonstrated that overexpression of ACACB was associated with free fatty acid accumulation in patients' myoblasts whereas malonyl-camitine (as a measure of malonyl-CoA) and CPT1 activity were in the normal range in basal conditions accordingly to the normal daily activity reported by the patients. Remarkably ACACB invalidation in patients' myoblasts decreased LD number and size while LPIN1 invalidation in controls induced LD accumulation. Further, pro-inflammatory treatments tumor necrosis factor alpha + Interleukin-1beta(TNF1 alpha + IL-1 beta) designed to mimic febrile illness, resulted in increased malonyl-camitine levels, reduced CPT1 activity and enhanced LD accumulation, a phenomenon reversed by dexamethasone and TNF alpha. or IL-1 beta inhibitors. Our data suggest that the pathogenic mechanism of rhabdomyolysis in lipin-1-deficient patients combines the predisposing constitutive impairment of lipid metabolism and its exacerbation by pro-inflammatory cytokines. (C) 2013 Published by Elsevier B.V.

To identify candidate key genes and pathways associated with lymph node tuberculosis (LNTB) and reveal the potential molecular mechanisms of LNTB development. Gene expression profile of GSE63548 was downloaded from the Gene Expression Omnibus (GEO) database. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichments of differentially expressed genes (DEGs) were analyzed by DAVID, and the protein-protein interaction (PPI) network was performed from STRING database. Furthermore, Cytoscape was used to integrate the network of transcription factor (TF) target and miRNA target. A total of 239 DEGs were screened out. Based on the DEGs, a miRNA of hsa-miR-4536 and 28 TFs, such as GATA1, JUND, NR2F1, POU1F1, and RELB, were obtained. Pathway enrichment analyses revealed that DEGs were mainly enriched in the pathways of regulation of lipolysis in adipocytes, vascular smooth muscle contraction, fat digestion and absorption, NOD-like receptor, and TNF signaling pathway. Furthermore, 53 nodes and 241 interactions were identified in the PPI network. In addition, the integrated regulatory network showed that CXCL9, CD36, LEP, ACACB, ALDH1A3, GPX3, STAT1, and LPL were the target genes of hsa-miR-4536. This study revealed the candidate key genes and pathways that are involved in the pathogenesis of LNTB, which will provide potential therapeutic targets for the treatment of LNTB.