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  1. Article ; Online: Studies on Ergothioneine. IX. Ergothioneine Stimulates Mouse Spermatozoa and Fertilization in vitro: (ergothioneine/fertilization/acrosome reaction/sperm penetration).

    Mayumi, Tadanori / Kawano, Hiroko / Kawai, Yuichi / Hama, Takao

    Development, growth & differentiation

    2023  Volume 26, Issue 6, Page(s) 563–569

    Abstract: The effects of ergothioneine on spermatozoa and ova were investigated in vitro and in vivo. Spermatozoa were treated with ergothioneine in vitro, and injected into the uterine cavity of female mice immediately after the induction of superovulation. The ... ...

    Abstract The effects of ergothioneine on spermatozoa and ova were investigated in vitro and in vivo. Spermatozoa were treated with ergothioneine in vitro, and injected into the uterine cavity of female mice immediately after the induction of superovulation. The ova were recovered 24 hr later and assessed for fertilization. Preincubation of spermatozoa with ergothioneine resulted in a significant increase in the fertilization rate. When ova were inseminated in the same manner in vitro with spermatozoa treated with 0.1 or 1.0 mM of ergothioneine, the penetration rate was significantly increased. These results suggest that ergothioneine is effective in inducing both capacitation and the acrosome reaction of mouse spermatozoa. Ergothioneine at concentrations of 0.1 and 1.0 mM in the preincubation medium was also effective in inducing the acrosome reaction of guinea pig spermatozoa. However, it had no significant effect on the development of 2-cell ova in vitro.
    Language English
    Publishing date 2023-06-06
    Publishing country Japan
    Document type Journal Article
    ZDB-ID 280433-5
    ISSN 1440-169X ; 0012-1592
    ISSN (online) 1440-169X
    ISSN 0012-1592
    DOI 10.1111/j.1440-169X.1984.00563.x
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article: Fatty acid 2-Hydroxylation in mammalian sphingolipid biology.

    Hama, Hiroko

    Biochimica et biophysica acta

    2009  Volume 1801, Issue 4, Page(s) 405–414

    Abstract: 2-Hydroxy fatty acids (hFA) are important components of a subset of mammalian sphingolipids. The presence of hFA in sphingolipids is best described in the nervous system, epidermis, and kidney. However, the literature also indicates that various hFA- ... ...

    Abstract 2-Hydroxy fatty acids (hFA) are important components of a subset of mammalian sphingolipids. The presence of hFA in sphingolipids is best described in the nervous system, epidermis, and kidney. However, the literature also indicates that various hFA-sphingolipids are present in additional tissues and cell types, as well as in tumors. Biosynthesis of hFA-sphingolipids requires fatty acid 2-hydroyxlase, and degradation of hFA-sphingolipids depends, at least in part, on lysosomal acid ceramidase and the peroxisomal fatty acid alpha-oxidation pathway. Mutations in the fatty acid 2-hydroxylase gene, FA2H, have been associated with leukodystrophy and spastic paraparesis in humans, underscoring the importance of hFA-sphingolipids in the nervous system. In the epidermis, hFA-ceramides are essential for the permeability barrier function. Physiological function of hFA-sphingolipids in other organs remains largely unknown. Recent evidence indicates that hFA-sphingolipids have specific roles in cell signaling.
    MeSH term(s) Animals ; Fatty Acids/metabolism ; Humans ; Hydroxylation ; Mixed Function Oxygenases/metabolism ; Sphingolipids/metabolism
    Chemical Substances Fatty Acids ; Sphingolipids ; Mixed Function Oxygenases (EC 1.-) ; fatty acid alpha-hydroxylase (EC 1.-)
    Language English
    Publishing date 2009-12-21
    Publishing country Netherlands
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Review
    ZDB-ID 60-7
    ISSN 1879-2596 ; 1879-260X ; 1872-8006 ; 1879-2642 ; 1879-2618 ; 1879-2650 ; 0006-3002 ; 0005-2728 ; 0005-2736 ; 0304-4165 ; 0167-4838 ; 1388-1981 ; 0167-4889 ; 0167-4781 ; 0304-419X ; 1570-9639 ; 0925-4439 ; 1874-9399
    ISSN (online) 1879-2596 ; 1879-260X ; 1872-8006 ; 1879-2642 ; 1879-2618 ; 1879-2650
    ISSN 0006-3002 ; 0005-2728 ; 0005-2736 ; 0304-4165 ; 0167-4838 ; 1388-1981 ; 0167-4889 ; 0167-4781 ; 0304-419X ; 1570-9639 ; 0925-4439 ; 1874-9399
    DOI 10.1016/j.bbalip.2009.12.004
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: 2'-Hydroxy ceramide in membrane homeostasis and cell signaling.

    Kota, Venkatesh / Hama, Hiroko

    Advances in biological regulation

    2013  Volume 54, Page(s) 223–230

    Abstract: Ceramide is a precursor of complex sphingolipids and also plays important roles in cell signaling. With the advances in lipid analytical technologies, the structural diversity of ceramide species have become evident, and the complexity of cellular ... ...

    Abstract Ceramide is a precursor of complex sphingolipids and also plays important roles in cell signaling. With the advances in lipid analytical technologies, the structural diversity of ceramide species have become evident, and the complexity of cellular metabolism and function associated with distinct ceramide species is beginning to be revealed. One of the common structural variations of ceramide is 2'-hydroxylation of the N-acyl chain. Fatty acid 2-hydroxylase (FA2H) is one of the enzymes that introduce the hydroxyl group during de novo synthesis of ceramide. FA2H is essential for the normal functioning of the nervous system, as evidenced by demyelinating disorder associated with FA2H mutations in humans and mice. Studies of Fa2h mutant mice indicate that lack of 2'-hydroxy galactosylceramide in the myelin membrane results in loss of long-term stability of myelin and eventual demyelination. FA2H also regulates differentiation of various cell types (epidermal keratinocytes, schwannoma cells, adipocytes). When provided exogenously, ceramide induces apoptosis in many cell types. Interestingly, the effective concentration of 2'-hydroxy ceramide that induces apoptosis is significantly lower compared to non-hydroxy ceramide, and cells die much more rapidly, suggesting that 2'-hydroxy ceramide can mediate proapoptotic signaling distinct from non-hydroxy ceramide. Collectively, current evidence clearly shows that 2'-hydroxy ceramide and 2'-hydroxy complex sphingolipids have unique functions in membrane homeostasis and cell signaling that could not be substituted by non-hydroxy counterparts.
    MeSH term(s) Animals ; Cell Membrane/metabolism ; Ceramides/chemistry ; Ceramides/metabolism ; Homeostasis ; Humans ; Mixed Function Oxygenases/genetics ; Mixed Function Oxygenases/metabolism ; Signal Transduction
    Chemical Substances Ceramides ; Mixed Function Oxygenases (EC 1.-)
    Language English
    Publishing date 2013-10-08
    Publishing country England
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Review
    ZDB-ID 2667413-0
    ISSN 2212-4934 ; 2212-4926
    ISSN (online) 2212-4934
    ISSN 2212-4926
    DOI 10.1016/j.jbior.2013.09.012
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article: Fatty acid 2-hydroxylase regulates cAMP-induced cell cycle exit in D6P2T schwannoma cells.

    Alderson, Nathan L / Hama, Hiroko

    Journal of lipid research

    2009  Volume 50, Issue 6, Page(s) 1203–1208

    Abstract: Sphingolipids are ubiquitous components of eukaryotic cells that regulate various cellular functions. In many cell types, a fraction of sphingolipids contain 2-hydroxy fatty acids, produced by fatty acid 2-hydroxylase (FA2H), as the N-acyl chain of ... ...

    Abstract Sphingolipids are ubiquitous components of eukaryotic cells that regulate various cellular functions. In many cell types, a fraction of sphingolipids contain 2-hydroxy fatty acids, produced by fatty acid 2-hydroxylase (FA2H), as the N-acyl chain of ceramide [hydroxyl fatty acid (hFA)-sphingolipids]. FA2H is highly expressed in myelin-forming cells of the nervous system and in epidermal keratinocytes. While hFA-sphingolipids are thought to enhance the physical stability of specialized membranes produced by these cells, physiological significance of hFA-sphingolipids in many other cell types is unknown. In this study, we report novel roles for FA2H and hFA-sphingolipids in the regulation of the cell cycle. Treatment of D6P2T Schwannoma cells with dibutyryl-cAMP (db-cAMP) induced exit from the cell cycle with concomitant upregulation of FA2H. Partial silencing of FA2H in D6P2T cells resulted in 60-70% reduction of hFA-dihydroceramide and hFA-ceramide, with no effect on nonhydroxy dihydroceramide and ceramide. Under these conditions, db-cAMP no longer induced cell cycle exit, and cells continued to grow and divide. Immunoblot analyses revealed that FA2H silencing prevented db-cAMP-induced upregulation of cyclin-dependent kinase inhibitors p21 and p27. These results provide evidence that FA2H is a negative regulator of the cell cycle and facilitates db-cAMP-induced cell cycle exit in D6P2T cells.
    MeSH term(s) Animals ; Bucladesine/pharmacology ; Cell Cycle/drug effects ; Cell Cycle/physiology ; Cell Line, Tumor ; Ceramides/metabolism ; Fatty Acids/metabolism ; Gene Silencing ; Mixed Function Oxygenases/antagonists & inhibitors ; Mixed Function Oxygenases/genetics ; Mixed Function Oxygenases/metabolism ; Neurilemmoma/enzymology ; Neurilemmoma/pathology ; RNA, Small Interfering/genetics ; Rats ; Sphingolipids/metabolism ; Up-Regulation/drug effects
    Chemical Substances Ceramides ; Fatty Acids ; RNA, Small Interfering ; Sphingolipids ; Bucladesine (63X7MBT2LQ) ; Mixed Function Oxygenases (EC 1.-) ; fatty acid alpha-hydroxylase (EC 1.-)
    Language English
    Publishing date 2009-01-22
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural
    ZDB-ID 80154-9
    ISSN 1539-7262 ; 0022-2275
    ISSN (online) 1539-7262
    ISSN 0022-2275
    DOI 10.1194/jlr.M800666-JLR200
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: Identification of C(6) -ceramide-interacting proteins in D6P2T Schwannoma cells.

    Kota, Venkatesh / Szulc, Zdzislaw M / Hama, Hiroko

    Proteomics

    2012  Volume 12, Issue 13, Page(s) 2179–2184

    Abstract: Ceramide is a bioactive molecule involved in numerous cell signaling pathways that are associated with cell cycle control, differentiation, senescence, and apoptosis. Although substantial knowledge about ceramide-regulated pathways has accumulated in the ...

    Abstract Ceramide is a bioactive molecule involved in numerous cell signaling pathways that are associated with cell cycle control, differentiation, senescence, and apoptosis. Although substantial knowledge about ceramide-regulated pathways has accumulated in the past decade, molecular mechanisms of ceramide action remain poorly understood, primarily due to limited information about ceramide-binding proteins. In the present study, we used affinity purification with a synthetic biotin-conjugated C(6) -ceramide analogue and LC-MS/MS to identify potential ceramide-interacting proteins in D6P2T Schwannoma cells. The purification resulted in identification of 97 unique proteins. The identified proteins are involved in various cellular processes, including apoptosis, cellular stress, cell cycle, cell differentiation, signaling, transcription, translation, protein biogenesis, metabolism, and transport.
    MeSH term(s) Animals ; Apoptosis ; Cell Cycle Checkpoints ; Cell Line, Tumor ; Ceramides/metabolism ; Chromatography, Liquid ; Neurilemmoma/metabolism ; Proteins/isolation & purification ; Proteins/metabolism ; Signal Transduction ; Tandem Mass Spectrometry
    Chemical Substances Ceramides ; Proteins ; N-(alpha-hydroxyoctadecanoyl)phytosphingosine (F1X8L2B00J)
    Language English
    Publishing date 2012-05-23
    Publishing country Germany
    Document type Journal Article ; Research Support, N.I.H., Extramural
    ZDB-ID 2032093-0
    ISSN 1615-9861 ; 1615-9853
    ISSN (online) 1615-9861
    ISSN 1615-9853
    DOI 10.1002/pmic.201100527
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: Landscape of driver mutations and their clinical effects on Down syndrome-related myeloid neoplasms.

    Sato, Tomohiko / Yoshida, Kenichi / Toki, Tsutomu / Kanezaki, Rika / Terui, Kiminori / Saiki, Ryunosuke / Ojima, Masami / Ochi, Yotaro / Mizuno, Seiya / Yoshihara, Masaharu / Uechi, Tamayo / Kenmochi, Naoya / Tanaka, Shiro / Matsubayashi, Jun / Kisai, Kenta / Kudo, Ko / Yuzawa, Kentaro / Takahashi, Yuka / Tanaka, Tatsuhiko /
    Yamamoto, Yohei / Kobayashi, Akie / Kamio, Takuya / Sasaki, Shinya / Shiraishi, Yuichi / Chiba, Kenichi / Tanaka, Hiroko / Muramatsu, Hideki / Hama, Asahito / Hasegawa, Daisuke / Sato, Atsushi / Koh, Katsuyoshi / Karakawa, Shuhei / Kobayashi, Masao / Hara, Junichi / Taneyama, Yuichi / Imai, Chihaya / Hasegawa, Daiichiro / Fujita, Naoto / Yoshitomi, Masahiro / Iwamoto, Shotaro / Yamato, Genki / Saida, Satoshi / Kiyokawa, Nobutaka / Deguchi, Takao / Ito, Masafumi / Matsuo, Hidemasa / Adachi, Souichi / Hayashi, Yasuhide / Taga, Takashi / Moriya Saito, Akiko / Horibe, Keizo / Watanabe, Kenichiro / Tomizawa, Daisuke / Miyano, Satoru / Takahashi, Satoru / Ogawa, Seishi / Ito, Etsuro

    Blood

    2024  

    Abstract: Transient abnormal myelopoiesis (TAM) is a common complication in newborns with Down syndrome (DS). It commonly progresses to myeloid leukemia (ML-DS) after spontaneous regression. In contrast to the favorable prognosis of primary ML-DS, patients with ... ...

    Abstract Transient abnormal myelopoiesis (TAM) is a common complication in newborns with Down syndrome (DS). It commonly progresses to myeloid leukemia (ML-DS) after spontaneous regression. In contrast to the favorable prognosis of primary ML-DS, patients with refractory/relapsed ML-DS have poor outcomes. However, the molecular basis for refractoriness and relapse, and the full spectrum of driver mutations in ML-DS remain largely unknown. We conducted a genomic profiling study of 143 TAM, 204 ML-DS, and 34 non-DS acute megakaryoblastic leukemia cases, including 39 ML-DS cases analyzed by exome sequencing. Sixteen novel mutational targets were identified in ML-DS samples. Of these, inactivations of IRX1 (16.2%) and ZBTB7A (13.2%) were commonly implicated in the upregulation of the MYC pathway and were potential targets for ML-DS treatment with bromodomain-containing protein 4 inhibitors. Partial tandem duplications of RUNX1 on chromosome 21 were also found, specifically in ML-DS samples (13.7%), presenting its essential role in DS leukemia progression. Finally, in 177 patients with ML-DS treated following the same ML-DS protocol (the Japanese Pediatric Leukemia and Lymphoma Study Group AML-D05/D11), CDKN2A, TP53, ZBTB7A, and JAK2 alterations were associated with a poor prognosis. Patients with CDKN2A deletions (n = 7) or TP53 mutations (n = 4) had substantially lower 3-year event-free survival [28.6% vs. 90.5%, P < 0.001; 25.0% vs. 89.5%, P < 0.001] than those without these mutations. These findings considerably change the mutational landscape of ML-DS, provide new insights into the mechanisms of progression from TAM to ML-DS, and help identify new therapeutic targets and strategies for ML-DS.
    Language English
    Publishing date 2024-03-21
    Publishing country United States
    Document type Journal Article
    ZDB-ID 80069-7
    ISSN 1528-0020 ; 0006-4971
    ISSN (online) 1528-0020
    ISSN 0006-4971
    DOI 10.1182/blood.2023022247
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article ; Online: NUTM2A-CIC fusion small round cell sarcoma: a genetically distinct variant of CIC-rearranged sarcoma.

    Sugita, Shintaro / Arai, Yasuhito / Aoyama, Tomoyuki / Asanuma, Hiroko / Mukai, Wakako / Hama, Natsuko / Emori, Makoto / Shibata, Tatsuhiro / Hasegawa, Tadashi

    Human pathology

    2017  Volume 65, Page(s) 225–230

    Abstract: CIC-rearranged sarcoma is a new entity of undifferentiated small round cell sarcoma characterized by chimeric fusions with CIC rearrangement. We report a NUTM2A-CIC fusion sarcoma in a 43-year-old woman who died of rapidly progressive disease. Histologic ...

    Abstract CIC-rearranged sarcoma is a new entity of undifferentiated small round cell sarcoma characterized by chimeric fusions with CIC rearrangement. We report a NUTM2A-CIC fusion sarcoma in a 43-year-old woman who died of rapidly progressive disease. Histologic analysis revealed multinodular proliferation of small round tumor cells with mild nuclear pleomorphism. The sclerotic fibrous septa separated the tumor into multiple nodules. Immunohistochemistry showed that the tumor cells were diffusely positive for vimentin, focally positive for cytokeratin, and negative for CD99 and NKX2.2. Tumor cells were also negative for ETV4, which was recently identified as a specific marker for CIC-rearranged sarcoma. High-throughput RNA sequencing of a formalin-fixed, paraffin-embedded clinical sample unveiled a novel NUTM2A-CIC fusion between NUTM2A exon 7 and CIC exon 12, and fluorescence in situ hybridization identified CIC and NUTM2A split signals. This case shared several clinicopathological findings with previously reported CIC-rearranged cases. We recognized the tumor as a genetically distinct variant of CIC-rearranged sarcomas with a novel NUTM2A-CIC fusion.
    MeSH term(s) Adult ; Biomarkers, Tumor/analysis ; Biomarkers, Tumor/genetics ; Cell Proliferation ; Disease Progression ; Exons ; Fatal Outcome ; Female ; Gene Fusion ; Gene Rearrangement ; Genetic Predisposition to Disease ; High-Throughput Nucleotide Sequencing ; Humans ; Immunohistochemistry ; In Situ Hybridization, Fluorescence ; Oncogene Proteins, Fusion/genetics ; Phenotype ; Repressor Proteins/genetics ; Reverse Transcriptase Polymerase Chain Reaction ; Sarcoma/chemistry ; Sarcoma/genetics ; Sarcoma/pathology ; Tumor Burden
    Chemical Substances Biomarkers, Tumor ; CIC protein, human ; NUTM2A-CIC fusion protein, human ; Oncogene Proteins, Fusion ; Repressor Proteins
    Language English
    Publishing date 2017-07
    Publishing country United States
    Document type Case Reports ; Journal Article
    ZDB-ID 207657-3
    ISSN 1532-8392 ; 0046-8177
    ISSN (online) 1532-8392
    ISSN 0046-8177
    DOI 10.1016/j.humpath.2017.01.012
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  8. Article ; Online: Successful hematopoietic stem cell transplantation from an HLA-mismatched parent for engraftment failure after unrelated cord blood transplantation in patients with juvenile myelomonocytic leukemia: Report of two cases.

    Akahane, Koshi / Watanabe, Atsushi / Furuichi, Yoshiyuki / Somazu, Shinpei / Oshiro, Hiroko / Goi, Kumiko / Sakashita, Kazuo / Muramatsu, Hideki / Hama, Asahito / Takahashi, Yoshiyuki / Koike, Kenichi / Kojima, Seiji / Sugita, Kanji / Inukai, Takeshi

    Pediatric transplantation

    2019  Volume 23, Issue 3, Page(s) e13378

    Abstract: JMML is an aggressive hematopoietic malignancy of early childhood, and allogeneic HSCT is the only curative treatment for this disease. Umbilical cord blood is one of donor sources for HSCT in JMML patients who do not have an HLA-compatible relative, but ...

    Abstract JMML is an aggressive hematopoietic malignancy of early childhood, and allogeneic HSCT is the only curative treatment for this disease. Umbilical cord blood is one of donor sources for HSCT in JMML patients who do not have an HLA-compatible relative, but engraftment failure remains a major problem. Here, we report two cases of JMML who were successfully rescued by HSCT from an HLA-mismatched parent after development of primary engraftment failure following unrelated CBT. Both patients had severe splenomegaly and underwent unrelated CBT from an HLA-mismatched donor. Immediately after diagnosis of engraftment failure, both patients underwent HSCT from their parent. For the second HSCT, we used RIC regimens consisting of FLU, CY, and a low dose of rabbit ATG with or without TBI and additionally administered ETP considering their persistent severe splenomegaly. Both patients achieved engraftment without severe treatment-related adverse effects. After engraftment of second HSCT, their splenomegaly was rapidly regressed, and both patients showed no sign of relapse for over 4 years. These observations demonstrate that HSCT from an HLA-mismatched parent could be a feasible salvage treatment for primary engraftment failure in JMML patients.
    MeSH term(s) Child, Preschool ; Cord Blood Stem Cell Transplantation/methods ; Female ; Fetal Blood ; HLA Antigens/immunology ; Hematopoietic Stem Cell Transplantation/methods ; Hematopoietic Stem Cells/cytology ; Hepatomegaly/surgery ; Humans ; Immunosuppressive Agents/therapeutic use ; Infant ; Leukemia, Myelomonocytic, Juvenile/therapy ; Male ; Mutation ; Recurrence ; Splenomegaly/surgery ; Transplantation Conditioning ; Treatment Outcome
    Chemical Substances HLA Antigens ; Immunosuppressive Agents
    Language English
    Publishing date 2019-02-20
    Publishing country Denmark
    Document type Case Reports
    ZDB-ID 1390284-2
    ISSN 1399-3046 ; 1397-3142
    ISSN (online) 1399-3046
    ISSN 1397-3142
    DOI 10.1111/petr.13378
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  9. Article ; Online: 2-Hydroxylated sphingomyelin profiles in cells from patients with mutated fatty acid 2-hydroxylase.

    Dan, Phyllis / Edvardson, Simon / Bielawski, Jacek / Hama, Hiroko / Saada, Ann

    Lipids in health and disease

    2011  Volume 10, Page(s) 84

    Abstract: Fatty acid 2-hydroxylase (FA2H) is the enzyme responsible for the hydroxylation of free fatty acids prior to their incorporation into 2-hydroxylated sphingolipids, which are the major constituents of the myelin leaflet. Mutated FA2H has been associated ... ...

    Abstract Fatty acid 2-hydroxylase (FA2H) is the enzyme responsible for the hydroxylation of free fatty acids prior to their incorporation into 2-hydroxylated sphingolipids, which are the major constituents of the myelin leaflet. Mutated FA2H has been associated with neurodegenerative diseases. Decreased FA2H activity was demonstrated only in vitro, but not in patient tissues. In this study we characterized the 2-hydroxylated sphingomyelin (SM) profiles in blood and fibroblasts from patients harboring a deleterious FA2H mutatation, and found that hydroxylated fatty acid sphingomyelin is present in normal amounts in patient lymphocytes, but decreased to a different extent in fibroblasts and erythrocytes.
    MeSH term(s) Case-Control Studies ; Chromatography, High Pressure Liquid ; Erythrocytes/metabolism ; Erythrocytes/pathology ; Fatty Acids/metabolism ; Fibroblasts/metabolism ; Fibroblasts/pathology ; Gene Expression Regulation, Enzymologic ; Humans ; Lymphocytes/enzymology ; Lymphocytes/pathology ; Mass Spectrometry ; Mixed Function Oxygenases/genetics ; Mutation/genetics ; RNA, Messenger/genetics ; RNA, Messenger/metabolism ; Sphingomyelins/metabolism
    Chemical Substances Fatty Acids ; RNA, Messenger ; Sphingomyelins ; Mixed Function Oxygenases (EC 1.-) ; fatty acid alpha-hydroxylase (EC 1.-)
    Language English
    Publishing date 2011-05-20
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ISSN 1476-511X
    ISSN (online) 1476-511X
    DOI 10.1186/1476-511X-10-84
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  10. Article: Fatty acid 2-hydroxylase regulates cAMP-induced cell cycle exit in D6P2T Schwannoma cells

    Alderson, Nathan L / Hama, Hiroko

    Journal of lipid research JLR. 2009 June, v. 50, no. 6

    2009  

    Abstract: Sphingolipids are ubiquitous components of eukaryotic cells that regulate various cellular functions. In many cell types, a fraction of sphingolipids contain 2-hydroxy fatty acids, produced by fatty acid 2-hydroxylase (FA2H), as the N-acyl chain of ... ...

    Abstract Sphingolipids are ubiquitous components of eukaryotic cells that regulate various cellular functions. In many cell types, a fraction of sphingolipids contain 2-hydroxy fatty acids, produced by fatty acid 2-hydroxylase (FA2H), as the N-acyl chain of ceramide [hydroxyl fatty acid (hFA)-sphingolipids]. FA2H is highly expressed in myelin-forming cells of the nervous system and in epidermal keratinocytes. While hFA-sphingolipids are thought to enhance the physical stability of specialized membranes produced by these cells, physiological significance of hFA-sphingolipids in many other cell types is unknown. In this study, we report novel roles for FA2H and hFA-sphingolipids in the regulation of the cell cycle. Treatment of D6P2T Schwannoma cells with dibutyryl-cAMP (db-cAMP) induced exit from the cell cycle with concomitant upregulation of FA2H. Partial silencing of FA2H in D6P2T cells resulted in 60-70% reduction of hFA-dihydroceramide and hFA-ceramide, with no effect on nonhydroxy dihydroceramide and ceramide. Under these conditions, db-cAMP no longer induced cell cycle exit, and cells continued to grow and divide. Immunoblot analyses revealed that FA2H silencing prevented db-cAMP-induced upregulation of cyclin-dependent kinase inhibitors p21 and p27. These results provide evidence that FA2H is a negative regulator of the cell cycle and facilitates db-cAMP-induced cell cycle exit in D6P2T cells.
    Language English
    Dates of publication 2009-06
    Size p. 1203-1208.
    Publishing place American Society for Biochemistry and Molecular Biology
    Document type Article
    ZDB-ID 80154-9
    ISSN 1539-7262 ; 0022-2275
    ISSN (online) 1539-7262
    ISSN 0022-2275
    Database NAL-Catalogue (AGRICOLA)

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