C6-Ceramide Enhances Phagocytic Activity of Kupffer Cells through the Production of Endogenous Ceramides

Choi, Jong Min; Chu, So Jung; Ahn, Kyong Hoon; Kim, Seok Kyun; Ji, Jung Eun; Won, Jong Hoon; Kim, Hyung Chul; Back, Moon Jung; Kim, Dae Kyong

doi:10.1007/s10059-011-1034-2

Cited by 7 publications

(4 citation statements)

References 39 publications

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“…Moreover, ceramide can regulate other cellular mechanisms such as phagocytosis and autophagy. First, permeable C(6)-ceramide increases the cellular levels of endogenous ceramides via a sphingosine-recycling pathway leading to enhanced phagocytosis by Kupffer cell [23]. Second, MCF7 cells deficient in autophagy protein that were sensitive to photodynamic therapy presented an increase in ceramide levels [24].…”

Section: Ceramide and Cellular Signalingmentioning

confidence: 99%

p53 and Ceramide as Collaborators in the Stress Response

Hage‐Sleiman

Esmerian

Kobeissy

et al. 2013

IJMS

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The sphingolipid ceramide mediates various cellular processes in response to several extracellular stimuli. Some genotoxic stresses are able to induce p53-dependent ceramide accumulation leading to cell death. However, in other cases, in the absence of the tumor suppressor protein p53, apoptosis proceeds partly due to the activity of this “tumor suppressor lipid”, ceramide. In the current review, we describe ceramide and its roles in signaling pathways such as cell cycle arrest, hypoxia, hyperoxia, cell death, and cancer. In a specific manner, we are elaborating on the role of ceramide in mitochondrial apoptotic cell death signaling. Furthermore, after highlighting the role and mechanism of action of p53 in apoptosis, we review the association of ceramide and p53 with respect to apoptosis. Strikingly, the hypothesis for a direct interaction between ceramide and p53 is less favored. Recent data suggest that ceramide can act either upstream or downstream of p53 protein through posttranscriptional regulation or through many potential mediators, respectively.

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Section: Ceramide and Cellular Signalingmentioning

confidence: 99%

p53 and Ceramide as Collaborators in the Stress Response

Hage‐Sleiman

Esmerian

Kobeissy

et al. 2013

IJMS

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“…Cancer tissues can break down endogenous Cer via ceramidases to sphingosine which can then be converted via sphingosine kinase into S1P, elevated levels of which are associated with propensity for drug resistance, aberrant proliferation, angiogenesis, and metastasis (1,2). In this regard, Cer chainlength clearly matters: Not only can exogenously delivered short-chain Cer increase levels of endogenous Cers (47), but it also displays greater potency in inducing cell death, and is slower to be glycosylated, than are longer-chain Cer species (33,48,49). Cer-RUB, shown to effectively deliver Cer for in vivo targeting of cancer cells, may improve treatments of at least some cancers, regardless of altered Cer-glycosylation or of the sphingolipid rheostat; however, testing this proposition first demands further preclinical studies.…”

Section: Discussionmentioning

confidence: 99%

Ceramide–Rubusoside Nanomicelles, a Potential Therapeutic Approach to Target Cancers Carrying p53 Missense Mutations

Khiste

Liu

Roy

et al. 2020

Molecular Cancer Therapeutics

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◥Ceramide (Cer) is an active cellular sphingolipid that can induce apoptosis or proliferation-arrest of cancer cells. Nanoparticle-based delivery offers an effective approach for overcoming bioavailability and biopharmaceutics issues attributable to the pronounced hydrophobicity of Cer. Missense mutations of the protein p53, which have been detected in approximately 42% of cancer cases, not only lose the tumor suppression activity of wild-type p53, but also gain oncogenic functions promoting tumor progression and drug resistance. Our previous works showed that cellular Cer can eradicate cancer cells that carry a p53 deletion-mutation by modulating alternative pre-mRNA splicing, restoring wild-type p53 protein expression. Here, we report that new ceramiderubusoside (Cer-RUB) nanomicelles considerably enhance Cer in vivo bioavailability and restore p53-dependent tumor suppression in cancer cells carrying a p53 missense mutation.Natural RUB encapsulated short-chain C 6 -Cer so as to form Cer-RUB nanomicelles ($32 nm in diameter) that substantially enhanced Cer solubility and its levels in tissues and tumors of mice dosed intraperitoneally. Intriguingly, Cer-RUB nanomicelle treatments restored p53-dependent tumor suppression and sensitivity to cisplatin in OVCAR-3 ovarian cancer cells and xenograft tumors carrying p53 R248Q mutation. Moreover, Cer-RUB nanomicelles showed no signs of significant nonspecific toxicity to noncancerous cells or normal tissues, including bone marrow. Furthermore, Cer-RUB nanomicelles restored p53 phosphorylated protein and downstream function to wild-type levels in p53 R172H /þ transgenic mice. Altogether, this study, for the first time, indicates that natural Cer-RUB nanomicelles offer a feasible approach for efficaciously and safely targeting cancers carrying p53 missense mutations.

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“…Mouse Kupffer cells were isolated by collagenase digestion and differential centrifugation, using Percoll as described previously [ 15 ]. Briefly, after the mouse was anesthetized with sodium pentobarbital, the abdomen was opened and the portal vein was cannulated with 16 G catheter.…”

Section: Methodsmentioning

confidence: 99%

Salvia-Nelumbinis Naturalis Formula Improved Inflammation in LPS Stressed Macrophages via Upregulating MicroRNA-152

Shu

Huang

et al. 2017

Mediators of Inflammation

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Salvia-Nelumbinis naturalis (SNN) formula is an effective agent in treating nonalcoholic steatohepatitis (NASH); however, the precise mechanisms are still undefined. Activation of Kupffer cells by gut-derived lipopolysaccharide (LPS) plays a central role in the pathogenesis of NASH. In the present study, we aimed to explore the epigenetic regulation of microRNAs under the beneficial effects of SNN-containing serum in LPS stressed macrophages. Kupffer cells were isolated from C57BL/6 mice and treated with LPS or LPS and SNN-containing serum; the mRNA expression of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) was assessed. By using microarray chips, we investigated differentially expressed microRNA profiles to decipher the underlining mechanisms of SNN-containing serum. It was revealed that SNN-containing serum decreased TNF-α and IL-6 expression, and microRNA-152 was identified as the potential epigenetic regulator. We further verified the pharmacological effects in Raw264.7 cells; while transfection with miRNA-152 mimics could reduce TNF-α and IL-6, transfection with miRNA-152 inhibitor blocked the anti-inflammatory effect of SNN-containing serum. These results suggested that SNN-containing serum could improve inflammation in LPS stressed Kupffer cells and macrophages via upregulating microRNA-152.

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C6-Ceramide Enhances Phagocytic Activity of Kupffer Cells through the Production of Endogenous Ceramides

Cited by 7 publications

References 39 publications

p53 and Ceramide as Collaborators in the Stress Response

p53 and Ceramide as Collaborators in the Stress Response

Ceramide–Rubusoside Nanomicelles, a Potential Therapeutic Approach to Target Cancers Carrying p53 Missense Mutations

Salvia-Nelumbinis Naturalis Formula Improved Inflammation in LPS Stressed Macrophages via Upregulating MicroRNA-152

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