Functions of Ceramide in Coordinating Cellular Responses to Stress

Hannun, Yusuf A.

doi:10.1126/science.274.5294.1855

Cited by 1,564 publications

(1,392 citation statements)

References 96 publications

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“…TNF-α can stimulate ceramide formation via the activation of both neutral and acid SMases, accompanied by ROS such as superoxide anion production [26]. TNF-α initiates the pathway through TNFR1 (55-kDa receptor) leading to phospholipase A2 activation, generation of arachidonic acid, and subsequent activation of SMase [27]. TNF-α-stimulated cells are redox-sensitive [28].…”

Section: Tumor Necrosis Factor-α and Ceramidementioning

confidence: 99%

Ceramide: A common pathway for atherosclerosis?

et al. 2008

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Plasma sphingomyelin concentration is correlated with the development of atherosclerosis. It has been found to exist in significantly higher concentrations in aortic plaque. This appears to have clinical relevance as well as it has been shown to be an independent predictor of coronary artery disease. Ceramide, the backbone of sphingolipids, is the key component which affects atherosclerotic changes through its important second-messenger role. This paper sheds light on some of the current literature supporting the significance of ceramide with respect to its interactions with lipids, inflammatory cytokines, homocysteine and matrix metalloproteinases. Furthermore, the potential therapeutic implications of modulating ceramide concentrations are also discussed.

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Section: Tumor Necrosis Factor-α and Ceramidementioning

confidence: 99%

Ceramide: A common pathway for atherosclerosis?

et al. 2008

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“…At low levels, ceramides are important for injury‐induced cytokine production and activating protein phosphatases and kinases, enzymes involved in stress signaling cascades (Hannun, 1996). However, at high levels, ceramides inhibit cell division and induce cellular dysfunction and apoptosis.…”

Section: Introductionmentioning

confidence: 99%

Demographic and clinical variables affecting mid‐ to late‐life trajectories of plasma ceramide and dihydroceramide species

et al. 2015

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SummaryIt has been increasingly recognized at the basic science level that perturbations in ceramide metabolism are associated with the development and progression of many age‐related diseases. However, the translation of this work to the clinic has lagged behind. Understanding the factors longitudinally associated with plasma ceramides and dihydroceramides (DHCer) at the population level and how these lipid levels change with age, and by sex, is important for the clinical development of future therapeutics and biomarkers focused on ceramide metabolism. We, therefore, examined factors cross‐sectionally and longitudinally associated with plasma concentrations of ceramides and DHCer among Baltimore Longitudinal Study of Aging participants (n = 992; 3960 total samples), aged 55 years and older, with plasma at a mean of 4.1 visits (range 2–6). Quantitative analyses were performed on a high‐performance liquid chromatography‐coupled electrospray ionization tandem mass spectrometer. Linear mixed models were used to assess the relationships between plasma ceramide and DHCer species and demographics, diseases, medications, and lifestyle factors. Women had higher plasma concentrations of most ceramide and DHCer species and showed steeper trajectories of age‐related increases compared to men. Ceramides and DHCer were more associated with waist–hip ratio than body mass index. Plasma cholesterol and triglycerides, prediabetes, and diabetes were associated with ceramides and DHCer, but the relationship showed specificity to the acyl chain length and saturation. These results demonstrate the importance of examining the individual species of ceramides and DHCer, and of establishing whether intra‐individual age‐ and sex‐specific changes occur in synchrony to disease onset and progression.

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“…Ceramide is a second messenger generated intracellularly by the sphingomyelinase-mediated cleavage of sphingomyelin [23,29,38]. Sphingomyelinase activity is strongly increased during developmental neuronal death in rat brain [54].…”

Section: Introductionmentioning

confidence: 99%

IGF-I protects cortical neurons against ceramide-induced apoptosis via activation of the PI-3K/Akt and ERK pathways; is this protection independent of CREB and Bcl-2?

Willaime‐Morawek

Arbez

Mariani

et al. 2005

Molecular Brain Research

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Current understanding of IGF-I-mediated neuroprotection implies the activation of phosphatidylinositol-3-kinase (PI-3K), which leads to the activation of Akt/Protein Kinase B. In non-neuronal cells, Akt phosphorylates and activates the transcription factor CREB, implicated in the transcription of the anti-apoptotic bcl-2 gene. This paper further analyses the anti-apoptotic IGF-I action in neurons. We show that IGF-I protects cortical neurons against ceramide-induced apoptosis. Ceramide decreases Akt phosphorylation during apoptotic process whereas a simultaneous treatment with IGF-I increases Akt phosphorylation. Analysis of the signal transduction pathways revealed that IGF-I induces CREB phosphorylation via PI-3K and ERK, whereas simultaneous ceramide and IGF-I treatment decreases CREB phosphorylation. Although an overexpression of Bcl-2 protects cortical neurons against ceramide-induced apoptosis, our data indicate that the Bcl-2 protein level is not modulated during IGF-I, ceramide and/or LY294002 treatment. In consequence, we demonstrated that IGF protects neurons against ceramide-induced apoptosis and that IGF-I protection involves the PI-3K/Akt and ERK pathways; this protection may be independent of CREB and Bcl-2. D

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Functions of Ceramide in Coordinating Cellular Responses to Stress

Cited by 1,564 publications

References 96 publications

Ceramide: A common pathway for atherosclerosis?

Ceramide: A common pathway for atherosclerosis?

Demographic and clinical variables affecting mid‐ to late‐life trajectories of plasma ceramide and dihydroceramide species

IGF-I protects cortical neurons against ceramide-induced apoptosis via activation of the PI-3K/Akt and ERK pathways; is this protection independent of CREB and Bcl-2?

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