Phospholipase D modulation by ceramide in senescence

Webb, Lisa; Arnholt, Alan T.; Venable, Mark E.

doi:10.1007/s11010-009-0294-z

Cited by 26 publications

(10 citation statements)

References 34 publications

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“…Ceramides are notable candidates for modulating aging because their concentration increases as mammals age and they are thought to play roles in age-related diseases including type 2 diabetes, cardiovascular and immune dysfunction, cancer and neurodegeneration [78- 84]. The strong correlation between ceramide accumulation and increased oxidative stress and insulin resistance are intriguing as these changes are thought to promote aging and age-associated diseases [7, 85-90].…”

Section: Roles For Sphingolipids In Modulating Lifespan In Mammalsmentioning

confidence: 99%

Sphingolipids and lifespan regulation

Huang

Withers

Dickson

2014

Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biolog

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Diseases including cancer, type 2 diabetes, cardiovascular and immune dysfunction and neurodegeneration become more prevalent as we age, and combined with the increase in average human lifespan, place an ever increasing burden on the health care system. In this chapter we focus on finding ways of modulating sphingolipids to prevent the development of age-associated diseases or delay their onset, both of which could improve health in elderly, fragile people. Reducing the incidence of or delaying the onset of diseases of aging has blossomed in the past decade because of advances in understanding signal transduction pathways and cellular processes, especially in model organisms, that are largely conserved in most eukaryotes and that can be modulated to reduce signs of aging and increase health span. In model organisms such interventions must also increase lifespan to be considered significant, but this is not a requirement for use in humans. The most encouraging interventions in model organisms involve lowering the concentration of one or more sphingolipid so as to reduce the activity of key signaling pathways, one of the most promising being the Target of Rapamycin Complex 1 (TORC1) protein kinase pathway. Other potential ways in which modulating sphingolipids may contribute to improving the health profile of the elderly is by reducing oxidative stresses, inflammatory responses and growth factor signaling. Lastly, perhaps the most interesting way to modulate sphingolipids and promote longevity is by lowering the activity of serine palmitoyltransferase, the first enzyme in the de novo sphingolipid biosynthesis pathway. Available data in yeasts and rodents are encouraging and as we gain insights into molecular mechanisms the strategies for improving human health by modulating sphingolipids will become more apparent.

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Section: Roles For Sphingolipids In Modulating Lifespan In Mammalsmentioning

confidence: 99%

Sphingolipids and lifespan regulation

Huang

Withers

Dickson

2014

Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biolog

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“…In general, growth factors, chemical agents, and environmental stresses generate ceramide in order to mediate proliferation, membrane receptor functions, immune inflammatory responses, differentiation, cell adhesion, growth arrest, or apoptosis [6,12,18–20]. Furthermore, there is evidence that ceramide mediates another terminal cellular event, senescence [21]. Indeed, ceramide contributes to senescence by activating the growth suppressor pathway through retinoblastoma (Rb) dephosphorylation and the mitogenic pathway mediated by c-Fos and AP-1 [22].…”

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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“…They have been implicated in a variety of biological processes, including senescence [1], inflammation [2], and apoptosis [3, 4]. Furthermore, the plasma levels of these compounds may be altered in age-related disorders such as Alzheimer’s disease [5, 6] and mild cognitive impairment [7].…”

Section: Introductionmentioning

confidence: 99%

Rapid evaluation of 25 key sphingolipids and phosphosphingolipids in human plasma by LC-MS/MS

2015

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We report on a new, sensitive, and fast LC-MS/MS method for the simultaneous determination of 25 key sphingolipid components in human plasma, including phosphorylated sphinganine and sphingosine, in a single 9-min run. This method enables an effective and high-throughput coverage of the metabolic changes involving the sphingolipidome during physiological or pathological states. The method is based on liquid–liquid extraction followed by reversed-phase LC-MS/MS. Exogenous odd-chain lipids are used as cost-effective but reliable internal standards. The method was fully validated in surrogate matrix and naive human plasma following FDA guidelines. Sample stability and dilution integrity were also tested and verified.Electronic supplementary materialThe online version of this article (doi:10.1007/s00216-015-8585-6) contains supplementary material, which is available to authorized users.

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Phospholipase D modulation by ceramide in senescence

Cited by 26 publications

References 34 publications

Sphingolipids and lifespan regulation

Sphingolipids and lifespan regulation

p53 and Ceramide as Collaborators in the Stress Response

Rapid evaluation of 25 key sphingolipids and phosphosphingolipids in human plasma by LC-MS/MS

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