The Role of Sphingolipids in Arachidonic Acid Metabolism

Nakamura, Hiroyuki; Murayama, Toshihiko

doi:10.1254/jphs.13r18cp

Cited by 41 publications

(34 citation statements)

References 30 publications

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“…Activation of the endocytosis machinery by LacCer and SM has been shown to change various cellular functions including signal transduction in the plasma membrane, and these compounds have various biological functions in endocytosis‐dependent and ‐independent manners . Ceramide metabolites including C1P, LacCer and SM had direct and diverse effects on the activity of cPLA 2 α , and NBD‐C6‐ceramide enhanced release of arachidonic acid in this study. The activation of cPLA 2 α in response to various stimuli including stress and cytokines is a major pathway for the release of arachidonic acid, a precursor of eicosanoids, and thus the enzyme plays an important role in several physiological functions .…”

Section: Discussionsupporting

confidence: 49%

“…Acetyl-C16-ceramide-NBD did not change the incorporation of [ 3 H]arachidonic acid into cells. Damage to organelle membranes such as the plasma membranes and Golgi membranes has been shown to reduce the integrity of these membranes; thus, the incorporation of arachidonic acid and regulation of cPLA 2 α activity coupled with cellular Ca 2+ homeostasis were disturbed in damaged cells (19,20,46). The normal incorporation of [ 3 H]arachidonic acid and low release of radioactivity from the labeled cells without the stimulation in acetyl-C16-ceramide-NBD-treated cells also support the weaker cytotoxicity of the ceramide.…”

Section: Advantages Of Acetyl-c16-ceramide-nbd As a Golgi Staining Inmentioning

confidence: 99%

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Trafficking of Acetyl‐C16‐Ceramide‐NBD with Long‐Term Stability and No Cytotoxicity into the Golgi Complex

Makiyama

Nakamura

Nagasaka

et al. 2015

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The Golgi complex plays a prominent role in the modification and sorting of lipids and proteins, and is a highly dynamic organelle that is dispersed and rearranged before and after mitosis. Several reagents including 4-nitrobenzo-2-oxa-1,3-diazole-labeled C6-ceramide (NBD-C6-ceramide, a ceramide having an NBD-bound C6-N-acyl chain) and Golgi-specific proteins that emit fluorescence are used as Golgi markers. In the present study, we synthesized a new ceramide analog, acetyl-C16-ceramide-NBD (a ceramide having an acetylated C-1 hydroxyl group, C16-N-acyl chain, and NBD-bound C15-sphingosine), and showed that it preferentially accumulated in the Golgi complex without cytotoxicity for over 24 h. Pathways for cellular uptake and interorganelle trafficking of acetyl-C16-ceramide-NBD were investigated. Acetyl-C16-ceramide-NBD was transported to the Golgi complex via ceramide transport proteins. In contrast to NBD-C6-ceramide, acetyl-C16-ceramide-NBD was resistant to ceramide metabolic enzymes such as sphingomyelin synthase and glucosylceramide synthase. Because of its weaker cytotoxicity and resistance to ceramide metabolic enzymes, the localization of the Golgi complex could be observed in acetyl-C16-ceramide-NBD-labeled cells before and after mitosis. Lipids including sphingolipids play a structural role in the cellular membranes, and regulate physiological and pathological conditions in cells and tissues and in vivo by themselves. The backbone structure of sphingolipids including ceramide is sphingosine, and sphingosine-1-phosphate (S1P, the phosphate ester of the C-1 position of sphingosine) is an important signaling molecule (1,2). Ceramide, which has an N-acyl chain at the C-2 position of sphingosine, is a central point from where various sphingolipids are synthesized and interconverted. The hydroxyl (OH) † These authors contributed equally to this work.group at the C-1 position of ceramide is modified by various enzymes: phosphorylation by ceramide kinase and glucosylation by glucosylceramide (GlcCer) synthase produce ceramide-1-phosphate (C1P) and GlcCer, respectively. Sphingomyelin (SM) synthase transfers a phosphocholine head group from phosphatidylcholine to the OH group at the C-1 position of ceramide and produces SM.Many studies previously reported the usefulness of fluorescence-labeled ceramides and ceramide-related molecules in the study of uptake systems and the intracellular traffic of molecules. 4-Nitrobenzo-2-oxa-1, 476 www.traffic.dk

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Section: Discussionsupporting

confidence: 49%

Section: Advantages Of Acetyl-c16-ceramide-nbd As a Golgi Staining Inmentioning

confidence: 99%

Trafficking of Acetyl‐C16‐Ceramide‐NBD with Long‐Term Stability and No Cytotoxicity into the Golgi Complex

Makiyama

Nakamura

Nagasaka

et al. 2015

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“…Liver is a vital organ and plays a key role in metabolism and detoxification. 38 12-HETE is an eicosanoid, a 5-lipoxygenase metabolite of arachidonic acid; 12-HETE is also associated with liver injury caused by lipid peroxidation. 37 Tryptophan is an essential amino acid and can be considered as a potential biomarker of chemical-induced liver injury.…”

Section: Discussionmentioning

confidence: 99%

The plasma metabolic profiling of chronic acephate exposure in rats via an ultra-performance liquid chromatography-mass spectrometry based metabonomic method

et al. 2015

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This study aimed to investigate the toxic effects of long-term, low-dose acephate administration on rats using ultra-performance liquid chromatography-mass spectrometry. A total of 120 male Wistar rats were randomly assigned to different groups: control; low-dose acephate (0.5 mg kg(-1) bw(-1)); middle-dose acephate (1.5 mg kg(-1) bw(-1)); and high-dose acephate (4.5 mg kg(-1) bw(-1)). The rats continuously received acephate via drinking water for 24 weeks. Rat plasma samples were collected at different time points to measure metabonomic profiles. Liver tissues were subjected to histopathological examination. The results showed that 10 metabolites in the plasma were significantly changed in the treated groups compared with those in the control group (P < 0.05 or P < 0.01). Exposure to acephate resulted in increased lysoPC (15 : 0), lysoPC (16 : 0), lysoPC (O-18 : 0), lysoPC (18 : 1(9Z)), lysoPC (18 : 0), lysoPC (20 : 4(5Z, 8Z, 11Z, 14Z)), arachidonic acid, and 12-HETE as well as decreased tryptophan and indoleacrylic acid in rat plasma. Moreover, the contents of high-density lipoprotein, low-density lipoprotein, triglyceride, total cholesterol, free fatty acids, and malondialdehyde, as well as the activities of superoxide dismutase and phospholipaseA2 in the serum, were significantly changed in the middle- and high-dose groups compared with those in the control group (P < 0.05 or P < 0.01). Histopathological examination results revealed that exposure to acephate may induce vacuolar degeneration in the liver cell cytoplasm, fat degeneration, and liver cell necrosis. These results indicated that exposure to acephate disrupted metabolism of lipids and amino acids, induced oxidative stress, caused neurotoxicity, and resulted in liver dysfunction.

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“…Nevertheless, because many lipid species in the same class are moving in concert, using this kit produced lipid measurements that characterized significant trends in the lipid species present in the infected samples. Sphingolipids are important signaling molecules involved in cellular growth, differentiation, inflammation, and immunity, including activation of cyclooxygenase (75,76). The sphingomyelin molecules were decreased in all the infected samples (Fig 6D, 6E).…”

Section: Metabolite Profile Indicates That the Middle Ear Is Immunosumentioning

confidence: 92%

Comprehensive Proteomic and Metabolomic Signatures of Nontypeable Haemophilus influenzae-Induced Acute Otitis Media Reveal Bacterial Aerobic Respiration in an Immunosuppressed Environment

Harrison

Dubois

John-Williams

et al. 2016

Molecular & Cellular Proteomics

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A thorough understanding of the molecular details of the interactions between bacteria and host are critical to ultimately prevent disease. Recent technological advances allow simultaneous analysis of host and bacterial protein and metabolic profiles from a single small tissue sample to provide insight into pathogenesis. We used the chinchilla model of human otitis media to determine, for the first time, the most expansive delineation of global changes in protein and metabolite profiles during an experimentally induced disease. After 48 h of infection with nontypeable Haemophilus influenzae, middle ear tissue lysates were analyzed by high-resolution quantitative two-dimensional liquid chromatography-tandem mass spectrometry. Dynamic changes in 105 chinchilla proteins and 66 metabolites define the early proteomic and metabolomic signature of otitis media. Our studies indicate that establishment of disease coincides with actin morphogenesis, suppression of inflammatory mediators, and bacterial aerobic respiration. We validated the observed increase in the actin-remodeling complex, Arp2/3, and experimentally showed a role for Arp2/3 in nontypeable Haemophilus influenzae invasion. Direct inhibition of actin branch morphology altered bacterial invasion into host epithelial cells, and is supportive of our efforts to use the information gathered to modify outcomes of disease. The twenty-eight nontypeable Haemophilus influenzae proteins identified participate in carbohydrate and amino acid metabolism, redox homeostasis, and include cell wall-associated metabolic proteins. Quantitative characterization of the molecular signatures of infection will redefine our understanding of host response driven developmental changes during pathogenesis. These data represent the first comprehensive study of host protein and metabolite profiles in vivo in response to infection and show the feasibility of extensive characterization of host protein profiles during disease. Identification of novel protein targets and metabolic biomarkers will advance development of therapeutic and diagnostic options for treatment of disease. Molecular & Cellular Proteomics 15: 10.1074/mcp.M115.052498, 1117-1138, 2016.Our current understanding of the global changes that occur during infection is primarily based upon transcriptional profiles of either the host or the bacteria. However, a significant component of disease progression is dependent upon posttranscriptional processes. Recent advances in the application of two-dimensional tandem mass spectrometry have dramatically increased sensitivity to allow simultaneous analyses of multiple molecules from very small biological samples. In this study, we report the comprehensive proteomic and metabolomic profiling of middle ear tissues using samples that are smaller than those typically obtained from a human biopsy. Proteomic and metabolomic analyses of samples as small as biopsies will revolutionize the elucidation of the mechanisms From the

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The Role of Sphingolipids in Arachidonic Acid Metabolism

Cited by 41 publications

References 30 publications

Trafficking of Acetyl‐C16‐Ceramide‐NBD with Long‐Term Stability and No Cytotoxicity into the Golgi Complex

Trafficking of Acetyl‐C16‐Ceramide‐NBD with Long‐Term Stability and No Cytotoxicity into the Golgi Complex

The plasma metabolic profiling of chronic acephate exposure in rats via an ultra-performance liquid chromatography-mass spectrometry based metabonomic method

Comprehensive Proteomic and Metabolomic Signatures of Nontypeable Haemophilus influenzae-Induced Acute Otitis Media Reveal Bacterial Aerobic Respiration in an Immunosuppressed Environment

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