Long chain ceramides and very long chain ceramides have opposite effects on human breast and colon cancer cell growth

Hartmann, Daniela; Lucks, Jessica; Fuchs, Sina; Schiffmann, Susanne; Schreiber, Yannick; Ferreiròs, Nerea; Merkens, Jennifer; Marschalek, Rolf; Geißlinger, Gerd; Grösch, Sabine

doi:10.1016/j.biocel.2011.12.019

Cited by 182 publications

(144 citation statements)

References 37 publications

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“…Our study shows that multiple ceramide and sphingomyelin species are increased during exposure of neonatal pups to hyperoxia. Long chain ceramides (Cer16:0, Cer18:0 and Cer20:0) have antiproliferative and pro-apoptotic effects [26], whereas very long chain ceramides (Cer22:0, Cer24:0 and Cer24:1) promote cell proliferation [27]. We observed an eightfold increase in long-chain Cer16:0 during hyperoxia, suggesting a role for increased apoptosis via ceramide signalling in this hyperoxia model.…”

Section: Discussionmentioning

confidence: 61%

Amelioration of hyperoxia-induced lung injury using a sphingolipid-based intervention

et al. 2012

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The aim of this study was to characterise lung function and bronchoalveolar lavage sphingolipid profile in newborn mice during hyperoxia exposure and recovery in room air, and to examine the effect of D-sphingosine supplementation during recovery.Newborn mice were exposed to 80% oxygen for 4 weeks and allowed to recover in room air for another 4 weeks. Lung function measurements and morphometrical analysis of lung tissue were performed and bronchoalveolar lavage fluid was collected during hyperoxia and recovery with and without D-sphingosine supplementation.Hyperoxia exposure altered lung function, which partially recovered in room air. Lungs had fewer and enlarged alveoli which persisted during recovery. Multiple sphingolipids were significantly increased after hyperoxia. Ceramides were increased after 2 weeks of recovery, but normalised to control values after 4 weeks. The addition of D-sphingosine during the first 5 days of recovery accelerated the normalisation of ceramide levels at 2 weeks and partially reversed the hyperoxia-induced increase in alveolar size and arrest in alveolarisation at 4 weeks.Exposure of newborn mice to hyperoxia caused restrictive and obstructive lung function changes that partially recovered in room air, while alveolar morphology remained abnormal. Hyperoxia increased ceramide levels, with normalisation after recovery. D-sphingosine addition during recovery reduced ceramide levels and ameliorated hyperoxia-induced alveolar arrest. @ERSpublications D-sphingosine during recovery reduced ceramide levels and ameliorated hyperoxia-induced alveolar arrest in mice

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Section: Discussionmentioning

confidence: 61%

Amelioration of hyperoxia-induced lung injury using a sphingolipid-based intervention

et al. 2012

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“…Although numerous studies have demonstrated a proapoptotic role for ceramides, the apoptotic functions of ceramides also depend on lipid structure. Dihydroceramide inhibits ceramide channel formation in isolated mitochondria ( 53 ), and long-chain and very long-chain ceramides have been shown to exhibit opposite effects toward cancer cell survival ( 54 ). Our discovery of preferential regulation of d18:2-Cers by BAX and BAK suggests that there could also exist distinct cellular ceramide pools with different infl uences over cellular viability, which we will investigate in future studies.…”

Section: Dko-elevated Metabolite Is D18:2/16:0 Ceramidementioning

confidence: 88%

Regulation of mitochondrial ceramide distribution by members of the BCL-2 family

Zhang

Barclay

Walensky

et al. 2015

Journal of Lipid Research

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“…The "many ceramides" paradigm hypothesizes that individual ceramide molecules are generated within distinct biochemical pathways and subcellular compartments to exert unique functions ( 45 ). For example, a recent study suggests a proapoptotic role of CerS1-generated C18:0-ceramide and prosurvival function of CerS6-generated C16:0-ceramide ( 47 ); however, an additional study has proposed that long-chain ceramides (C16:0, C18:0, C20:0) are antiproliferative, whereas very long chain ceramides (C24:0, C24:1) promote cell proliferation ( 48 ). Continued investigation Fig.…”

Section: Ceramidementioning

confidence: 99%

Sphingolipids: regulators of crosstalk between apoptosis and autophagy

Young

Kester

Wang

2013

Journal of Lipid Research

287

263

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decades ago, pioneering work by Hannun et al. and Kolesnick et al. established the foundation for the bioactive nature of sphingolipids by demonstrating the inhibition of protein kinase C (PKC) by sphingosine and the stimulation of a ceramide-activated protein kinase in response to tumor necrosis factor (TNF)-␣ , respectively ( 1, 2 ). Sphingolipids have since been recognized as critical activators or inhibitors of various protein kinases and phosphatases, receptors, and ion transporters ( 3 ). Moreover, sphingolipids have been identifi ed as key regulators of a vast number of cellular processes, including cell growth, adhesion, migration, senescence, apoptosis, and most recently, autophagy ( 3, 4 ).Much of the investigation into sphingolipid signaling has focused on the disparate nature of ceramide and sphingosine-1-phosphate (S1P). Ceramide is typically associated with growth arrest and apoptosis, while S1P promotes cell proliferation and survival. The opposing nature and dynamic balance of intracellular ceramide and S1P, termed the "sphingolipid rheostat," has been proposed to determine cell fate ( 5 ). However, emerging evidence and extensive characterization of the sphingolipid metabolic network suggests that this two-dimensional model does not adequately refl ect sphingolipid signaling and function within the cell. In addition to ceramide and S1P, other sphingolipid metabolites, such as sphingosine, dihydroceramide, and gangliosides, have been implicated in the regulation of apoptosis and macroautophagy (hereafter referred to as autophagy). Although autophagy is typically considered to be a cytoprotective mechanism for the suppression of apoptosis, recent evidence indicates that autophagy can also promote cell death ( 6 ). Due to the differential regulation of apoptosis and autophagy by sphingolipid metabolites, the sphingolipid network has emerged as a novel molecular switch between the apoptotic and autophagic Abstract Apoptosis and autophagy are two evolutionarily conserved processes that maintain homeostasis during stress. Although the two pathways utilize fundamentally distinct machinery, apoptosis and autophagy are highly interconnected and share many key regulators. The crosstalk between apoptosis and autophagy is complex, as autophagy can function to promote cell survival or cell death under various cellular conditions. The molecular mechanisms of crosstalk are beginning to be elucidated and have critical implications for the treatment of various diseases, such as cancer. Sphingolipids are a class of bioactive lipids that mediate many key cellular processes, including apoptosis and autophagy. By targeting several of the shared regulators, sphingolipid metabolites differentially regulate the induction of apoptosis and autophagy. Importantly, individual sphingolipid species appear to "switch" autophagy toward cell survival (e.g., sphingosine-1-phosphate) or cell death (e.g., ceramide, gangliosides). This review assesses the current understanding of sphingolipid-induced apoptosis and autophagy to addr...

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Long chain ceramides and very long chain ceramides have opposite effects on human breast and colon cancer cell growth

Cited by 182 publications

References 37 publications

Amelioration of hyperoxia-induced lung injury using a sphingolipid-based intervention

Amelioration of hyperoxia-induced lung injury using a sphingolipid-based intervention

Regulation of mitochondrial ceramide distribution by members of the BCL-2 family

Sphingolipids: regulators of crosstalk between apoptosis and autophagy

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