Lipidomics reveals carnitine palrnitoyltransferase 1C protects cancer cells from lipotoxicity and senescence / 药物分析学报

Lipotoxicity,caused by intracellular lipid accumulation,accelerates the degenerative process of cellular senescence,which has implications in cancer development and therapy.Previously,camitine palmi-toyltransferase 1C (CPT1C),a mitochondrial enzyme that catalyzes carnitinylation of fatty acids,was found to be a critical regulator of cancer cell senescence.However,whether loss of CPT1C could induce senescence as a result of lipotoxicity remains unknown.An LC/MS-based lipidomic analysis of PANC-1,MDA-MB-231,HCT-116 and A549 cancer cells was conducted after siRNA depletion of CPT1C.Cellular lipotoxicity was further confirmed by lipotoxicity assays.Significant changes were found in the lipidome of CPT1 C-depleted cells,including major alterations in fatty acid,diacylglycerol,triacylglycerol,oxidative lipids,cardiolipin,phosphatidylglycerol,phosphatidylcholine/phosphatidylethanolamine ratio and sphingomyelin.This was coincident with changes in expressions of mRNAs involved in lipogenesis.Histological and biochemical analyses revealed higher lipid accumulation and increased malondialde-hyde and reactive oxygen species,signatures of lipid peroxidation and oxidative stress.Reduction of ATP synthesis,loss of mitochondrial transmembrane potential and down-regulation of expression of mito-chondriogenesis gene mRNAs indicated mitochondrial dysfunction induced by lipotoxicity,which could further result in cellular senescence.Taken together,this study demonstrated CPT1C plays a critical role in the regulation of cancer cell lipotoxicity and cell senescence,suggesting that inhibition of CPT1C may serve as a new therapeutic strategy through induction of tumor lipotoxicity and senescence.

Giant perivascular spaces: two case reports

Giant perivascular spaces or Virchow-Robin spaces (VRSs) are uniquely inherent developmental malformation and are generally lined by ependymal or leptomeningeal cells. The cerebral hemispheres with VRSs present multiple cysts of curvilinear, round, oval, or layered configuration, which have the same signal intensity as the cerebrospinal fluid (CSF) and represent extremely dilated VRSs. The cortex became extremely thin with a well-defined margin. Herein, we report two cases of true giant perivascular spaces and present a review of pertinent literature. A patient has multiple cysts in the unilateral and bilateral and has polycystic liver. The clinical presentation, image logical features, and diagnosis are discussed.