Sphingolipids in mitochondria

Hernández-Corbacho, María José; Salama, Mohamed; Canals, Daniel; Senkal, Can E.; Obeid, Lina M.

doi:10.1016/j.bbalip.2016.09.019

Cited by 108 publications

(86 citation statements)

References 149 publications

(182 reference statements)

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“…Sphingolipids are building blocks of the mitochondrial membranes, where they exert various structural and functionrelated tasks. 23,32 Hence, their production can be seen as a proxy for the generation of mitochondria at early time points. Our results therefore suggest that by producing mitochondria, cardiomyocyte differentiation lays the foundation for enabling beta-oxidation of fatty acids, which indeed was detected at later stages of differentiation by our GO analysis.…”

Section: Discussionmentioning

confidence: 99%

Quantitative proteomics and systems analysis of cultured H9C2 cardiomyoblasts during differentiation over time supports a ‘function follows form’ model of differentiation

et al. 2018

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The rat cardiomyoblast cell line H9C2 has emerged as a valuable tool for studying cardiac development, mechanisms of disease and toxicology. We present here a rigorous proteomic analysis that monitored the changes in protein expression during differentiation of H9C2 cells into cardiomyocyte-like cells over time. Quantitative mass spectrometry followed by gene ontology (GO) enrichment analysis revealed that early changes in H9C2 differentiation are related to protein pathways of cardiac muscle morphogenesis and sphingolipid synthesis. These changes in the proteome were followed later in the differentiation time-course by alterations in the expression of proteins involved in cation transport and beta-oxidation.

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Section: Discussionmentioning

confidence: 99%

Quantitative proteomics and systems analysis of cultured H9C2 cardiomyoblasts during differentiation over time supports a ‘function follows form’ model of differentiation

et al. 2018

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“…These changes affect both the arrangement and properties of the membrane proteins, such as receptors, transporters, and signaling complexes that will transmit the signal further down the line (Edmond et al, 2015; Lockshon et al, 2012). In addition, both short- and long-chain ceramides were able to form stable ceramide channels in planar membranes in vitro, though the experimental evidence for this process in vivo is still missing (Hernandez-Corbacho, Salama, Canals, Senkal, & Obeid, 2017; Siskind & Colombini, 2000). Alternatively, ceramide elevation resulting from treatment of A549 cells with methotrexate caused ER (endoplasmic reticulum) membrane aggregation leading to apoptosis (Fekry, Esmaeilniakooshkghazi, Krupenko, & Krupenko, 2016).…”

Section: Ceramide Signaling: Mechanismsmentioning

confidence: 99%

Ceramide Signaling and p53 Pathways

Jeffries¹,

Krupenko

2018

Advances in Cancer Research

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Ceramides, important players in signal transduction, interact with multiple cellular pathways, including p53 pathways. However, the relationship between ceramide and p53 is very complex, and mechanisms underlying their coregulation are diverse and not fully characterized. The role of p53, an important cellular regulator and a transcription factor, is linked to its tumor suppressor function. Ceramides are involved in the regulation of fundamental processes in cancer cells including cell death, proliferation, autophagy, and drug resistance. This regulation, however, can be pro-death or pro-survival depending on cancer type, the balance between ceramide species, the rate of their synthesis and utilization, and the availability of a specific array of downstream targets. This chapter highlights the central role of ceramide in sphingolipid metabolism, its role in cancer, specific effectors in ceramide pathways controlled by p53, and coregulation of ceramide and p53 signaling. We discuss the recent studies, which underscore the function of p53 in the regulation of ceramide pathways and the reciprocal regulation of p53 by ceramide. This complex relationship is based on several molecular mechanisms including the p53-dependent transcriptional regulation of enzymes in sphingolipid pathways, the activation of mutant p53 through ceramide-mediated alternative splicing, as well as modulation of the p53 function through direct and indirect effects on p53 coregulators and downstream targets. Further insight into the connections between ceramide and p53 will allow simultaneous targeting of the two pathways with a potential to yield more efficient anticancer therapeutics.

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“…Sphingolipid metabolism is vitally important for the regulation of cell proliferation, aging and differentiation. 55,56 Furthermore, VEGF has the strongest promoting effect on the growth of endothelial cells and is one of the most important cytokines for promoting angiogenesis. Grosjean et al 57 have shown that VEGF could protect vascular endothelial cells from apoptosis.…”

Section: Discussionmentioning

confidence: 99%

Transcriptomic analysis on responses of the liver and kidney of finishing pigs fed cadmium contaminated rice

Xia

Ren

et al. 2018

J Sci Food Agric

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BACKGROUNDCadmium (Cd) is a common harmful substance that has many deleterious effects on the liver and kidney. Most reports about Cd toxic studies focused on its inorganic status, whereas the toxicity of Cd in organic materials is less studied. Here, we performed RNA‐seq to explore the influences of Cd contaminated rice on function of the liver and kidney of finishing pigs.RESULTSThe concentration of Cd in liver and kidney of pigs fed Cd contaminated rice increased by 4.00 and 2.94 times, respectively, compared to those in the control group. With transcriptomic analysis, approximately 4–6 × 107 clean reads were acquired. Five differently expressed genes (DEGs) were identified in the liver, and 12 DEGs in the kidney. SPHK2 was commonly down‐regulated. No significantly enriched gene ontology (GO) terms were identified. By Kyoto encyclopaedia of genes and genomes (KEGG) enrichments, four pathways were identified in hepatic tissue, and five pathways in nephritic tissue. Intriguingly, two pathways (sphingolipid metabolism and VEGF signalling pathway) were altered both in the liver and kidney.CONCLUSIONCd contaminated rice may cause liver and kidney damage and inflammation, or even lead to more severe harm to these tissues. © 2017 Society of Chemical Industry

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Sphingolipids in mitochondria

Cited by 108 publications

References 149 publications

Quantitative proteomics and systems analysis of cultured H9C2 cardiomyoblasts during differentiation over time supports a ‘function follows form’ model of differentiation

Quantitative proteomics and systems analysis of cultured H9C2 cardiomyoblasts during differentiation over time supports a ‘function follows form’ model of differentiation

Ceramide Signaling and p53 Pathways

Transcriptomic analysis on responses of the liver and kidney of finishing pigs fed cadmium contaminated rice

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