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torsdag 22 mars 2018

Palmitiinihaposta harkittavaksi asiaa

The mitochondrial damage-cGAS-STING-IRF3 pathway is critically involved in metabolic stress-induced endothelial inflammation.
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fredag 2 mars 2018

MBP, tau ja mikrotubulit

Glia. 2015 Sep;63(9):1621-35. doi: 10.1002/glia.22832. Epub 2015 Apr 4.

Downregulation of the microtubule associated protein tau impairs process outgrowth and myelin basic protein mRNA transport in oligodendrocytes.

Seiberlich V1, Bauer NG1,2, Schwarz L1, Ffrench-Constant C2, Goldbaum O1, Richter-Landsberg C1.

Abstract

Oligodendrocytes, the myelin forming cells of the CNS, are characterized by their numerous membranous extensions, which enwrap neuronal axons and form myelin sheaths. During differentiation oligodendrocytes pass different morphological stages, downregulate the expression of the proteoglycan NG2, and acquire major myelin specific proteins, such as myelin basic proteins (MBP) and proteolipid protein (PLP).

MBP mRNA is transported in RNA granules along the microtubules (MTs) to the periphery and translated locally. MTs participate in the elaboration and stabilization of the myelin forming extensions and are essential for cellular sorting processes. Their dynamic properties are regulated by microtubule associated proteins (MAPs).

 The MAP tau is present in oligodendrocytes and involved in the regulation and stabilization of the MT network. To further elucidate the functional significance of tau in oligodendrocytes, we have downregulated tau by siRNA technology and studied the effects on cell differentiation and neuron-glia contact formation. The data show that tau knockdown impairs process outgrowth and leads to a decrease in MBP expression.
 Furthermore, MBP mRNA transport to distant cellular extensions is impaired and cells remain in the NG2 stage. In myelinating cocultures with dorsal root ganglion neurons, oligodendrocyte precursor cells after tau miR RNA lentiviral knockdown develop into NG2 positive cells with very long and thin processes, contacting axons loosely, but fail to form internodes. This demonstrates that tau is important for MBP mRNA transport and involved in process formation. The disturbance of the balance of tau leads to abnormalities in oligodendrocyte differentiation, neuron-glia contact formation and the early myelination process. KEYWORDS:
Fyn kinase; NG2 cells; microtubule bundling; myelination; neuron-glia interaction; rat brain



(2)

Biol Chem. 2016 Mar;397(3):185-94. doi: 10.1515/hsz-2015-0157.

Protein aggregate formation in oligodendrocytes: tau and the cytoskeleton at the intersection of neuroprotection and neurodegeneration.

Richter-Landsberg C.
Oligodendrocytes are dependent on an intact, dynamic microtubule (MT) network, which participates in the elaboration and stabilization of myelin forming extensions, and is essential for cellular sorting processes. The microtubule-associated protein tau is constituent of oligodendrocytes. During culture maturation it is developmentally regulated and important for MT stability, MT formation and intracellular trafficking. Downregulation of tau impairs process outgrowth and the transport of myelin basic protein (MBP) mRNA to the cell periphery. Cells fail to differentiate into MBP-expressing, sheet-forming oligodendrocytes. Tau-positive inclusions originating in oligodendrocytes and white matter pathology are prominent in frontotemporal dementias, such as Pick's disease, progressive supranuclear palsy and corticobasal degeneration.

An impairment or overload of the proteolytic degradation systems, i.e. the ubiquitin proteasomal system and the lysosomal degradation pathway, has been connected to the formation of protein aggregates. Large protein aggregates are excluded from the proteasome and degraded by autophagy, which is a highly selective process and requires receptor proteins for ubiquitinated proteins, including histone deacetylase 6 (HDAC6). HDAC6 is present in oligodendrocytes, and α-tubulin and tau are substrates of HDAC6.

  In this review our current knowledge of the role of tau and protein aggregate formation in oligodendrocyte cell culture systems is summarized.
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Myelin basic protein

Alzheimers Res Ther. 2018 Jan 9;10(1):1. doi: 10.1186/s13195-017-0329-8.

Diffusion kurtosis imaging allows the early detection and longitudinal follow-up of amyloid-β-induced pathology.

Praet J1, Manyakov NV2, Muchene L3, Mai Z1,4, Terzopoulos V4,5, de Backer S6, Torremans A7, Guns PJ1,8, Van De Casteele T2, Bottelbergs A2, Van Broeck B2, Sijbers J9, Smeets D1,4, Shkedy Z3, Bijnens L2, Pemberton DJ2, Schmidt ME2, Van der Linden A1, Verhoye M10.

Abstract

BACKGROUND:

Alzheimer's disease (AD) is a progressive neurodegenerative disorder and the most common cause of dementia in the elderly population. In this study, we used the APP/PS1 transgenic mouse model to explore the feasibility of using diffusion kurtosis imaging (DKI) as a tool for the early detection of microstructural changes in the brain due to amyloid-β (Aβ) plaque deposition.

METHODS:

We longitudinally acquired DKI data of wild-type (WT) and APP/PS1 mice at 2, 4, 6 and 8 months of age, after which these mice were sacrificed for histological examination. Three additional cohorts of mice were also included at 2, 4 and 6 months of age to allow voxel-based co-registration between diffusion tensor and diffusion kurtosis  metrics and immunohistochemistry.

RESULTS:

Changes were observed in diffusion tensor (DT) and diffusion kurtosis (DK) metrics in many of the 23 regions of interest that were analysed. Mean and axial kurtosis were greatly increased owing to Aβ-induced pathological changes in the motor cortex of APP/PS1 mice at 4, 6 and 8 months of age. Additionally, fractional anisotropy (FA) was decreased in APP/PS1 mice at these respective ages. Linear discriminant analysis of the motor cortex data indicated that combining diffusion tensor and diffusion kurtosis metrics permits improved separation of WT from APP/PS1 mice compared with either diffusion tensor or diffusion kurtosis metrics alone. We observed that mean kurtosis and FA are the critical metrics for a correct genotype classification.
 Furthermore, using a newly developed platform to co-register the in vivo diffusion-weighted magnetic resonance imaging with multiple 3D histological stacks, we found high correlations between DK metrics and anti-Aβ (clone 4G8) antibody,
 glial fibrillary acidic protein (GFAP),
 ionised calcium-binding adapter molecule 1
 and myelin basic protein (MBP)  immunohistochemistry.
 Finally, we observed reduced FA in the septal nuclei of APP/PS1 mice at all ages investigated.
 The latter was at least partially also observed by voxel-based statistical parametric mapping, which showed significantly reduced FA in the septal nuclei, as well as in the corpus callosum, of 8-month-old APP/PS1 mice compared with WT mice.

CONCLUSIONS:

Our results indicate that DKI metrics hold tremendous potential for the early detection and longitudinal follow-up of Aβ-induced pathology.

KEYWORDS:

APP/PS1; Alzheimer’s disease; Diffusion kurtosis imaging; Diffusion tensor imaging; Magnetic resonance imaging
PMID:
29370870
DOI:
10.1186/s13195-017-0329-8
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Selkäytimen demyelinoitumisen vaara huumeen käyttäjillä

Front Neurol. 2018 Feb 6;9:49. doi: 10.3389/fneur.2018.00049. eCollection 2018.

Thioredoxin-1 Protects Spinal Cord from Demyelination Induced by Methamphetamine through Suppressing Endoplasmic Reticulum Stress and Inflammation. Yang L1,2,3, Guo Y2, Huang M2, Wu X2, Li X2, Chen G2, Li Y2, Bai J2.

Tiivistelmä: Abstract

Kautta maailman  huumeena käytetty  psykostomulantti  on metyyli-amfetamiini (meth) . Siitä on alkanut kertyä vakavaa tietoa:  se aiheuttaa aivovauriota. Muutama harva tutkija  on raportoinut myös demyelinisoitumisesta ( siis  hermoston eristävän kaapeliaineksen heikentymisestä. 

Tässä artikkelissa  tiedotetaan että  tioredoxiini-1/Trx-1 ( kehon redox-järjestelmään kuuluva proteiini)  pystyy suojelemaan hermosoluja eri stressitiloissa. Mutta siitä ei ole aiemmin   selvitetty, voisiko, se ehkä  vastavaikuttaa  myös metamfetamiinin aiheuttamaan demyelinoitumiseen.

  • Methamphetamine (METH) is a psychostimulant abused around the world. Emerging evidence indicates that METH causes brain damage. However, there are very few reports on METH-induced demyelination. Thioredoxin-1 (Trx-1) is a redox regulating protein and plays the roles in protecting neurons from various stresses. However, whether Trx-1 resists demyelination induced by METH has not been reported. 
Tässä tutkimuksessa  havaittiin hiiriltä  ensinnäkin, että metamfetamiini ohentaa niiden  selkäytimen myeliinituppeja. Jos hiireen siirrettiin (transgeenisesti)  trx-1- geenin yliesiintymä,  niillä  kuitenkin tuon  huumeen  heikentämä  myeliinituppi pystyi korjaantumaan normaaliin vahvuuteen.
Myeliiniproteiineja ovat MAG ( myeliiniin assosioituva glykoproteiini) ja  MBP ( myeliinin emäksinen proteiini). Niiden esiintymä vähenee  metamfetamiinista, samoin väheni kinaasientsyymi  CDK5. Mutta näitä muutoksia blokeerasi  Trx-1 hiirissä.
  • In this study, we found that METH-induced thin myelin sheaths in spinal cord, whereas Trx-1 overexpression transgenic (TG) mice restored the myelin sheaths thickness. The expressions of myelin-associated glycoprotein, myelin basic protein, and cyclin-dependent kinase 5 were decreased by METH, whereas these alterations were blocked in Trx-1 TG mice.
 Metamfetamiini vähensi prokaspaasi-12- ja prokaspaasi-3- määriä ja lisäsi calpaiini-1 määrää. Näihin  muutoksiin vastavaikutti Trx-2 TG-hiirissä. Samoin metamfetamiini  indusoi  extrasellulaarissta signaalia säätelevän kinaasin, NF-kB tumatekijän, TNF-alfan ja IL1-betan . Näihinkin muutoksiin  Trx-1 vaikutti TG-hiirissä.
  •  The expressions of procaspase-12 and procaspase-3 were decreased by METH, the expression of calpain1 was increased by METH, whereas the alterations were suppressed in Trx-1 TG mice. As same as, the expressions of the extracellular signal-regulated kinase, nuclear factor κB, tumor necrosis factor-alpha, and interleukin-1beta were induced by METH, which were suppressed in Trx-1 TG mice. 
 Johtopäätöksenä:  Trx-1  saattaa olla kehossa  metamfetamiininvälitteisen selkäydindemyelinisaation kriittinen vastavaikuttaja  säätelemällä  endoplasmisen retikulumin stressiä ja  tulehduksellisia teitä.
  • These data suggest that Trx-1 may play a critical role in resisting the METH-mediated demyelination in spinal cord through regulating endoplasmic reticulum stress and inflammation pathways.

Avainsanoja,KEYWORDS:

demyelination; endoplasmic reticulum stress; inflammation; methamphetamine; spinal cord; thioredoxin-1
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Luteiini , zeaxantiini, DHA, kognitio

https://www.ncbi.nlm.nih.gov/pubmed/29049383

PLoS One. 2017 Oct 19;12(10):e0186767. doi: 10.1371/journal.pone.0186767. eCollection 2017.

Lutein accumulates in subcellular membranes of brain regions in adult rhesus macaques: Relationship to DHA oxidation products.

Mohn ES1, Erdman JW Jr2, Kuchan MJ3, Neuringer M4, Johnson EJ1.

Tiivistelmä, Abstract

 LUTEIINI on karotenoidi, jolla on antioksidatiivista funktiota ja kädellisillä sitä tapaa kertyä  aivoon;  ihmisellä se korreloi kognitioon. Omega3 rasvahappo DHA on myöskin kognitiolle edullista, mutta  se on altis oksidoitumaan. Tässä tutkimuksessa selvitetään luteiinin sijoittumista kognitiolle tärkeisiin  aivoalueisiin ja  määritetään, onko  se assosioitunut aivojen PUFA  rasvahappojen oksidoitumiseen jollain tavalla.
  • Lutein, a carotenoid with anti-oxidant functions, preferentially accumulates in primate brain and is positively related to cognition in humans. Docosahexaenoic acid (DHA), an omega-3 polyunsaturated fatty acid (PUFA), is also beneficial for cognition, but is susceptible to oxidation. The present study characterized the membrane distribution of lutein in brain regions important for different domains of cognitive function and determined whether membrane lutein was associated with brain PUFA oxidation.
 Aikuiselle rhesusapinoille  syötettiin kahta  rehulaatua, jossa toisessa  oli luteiini/zeaxantiinilisää.
a)   rehua (sisälsi   noin 2 mg luteiinia  kiloa kohden päivässä eli  0,5 umol/kg).
 b)  rehua ja   luteiinilisää 4.5 mg/ kg eli 1umol/kg päivässä ja zeaxantiinia 0.5 mg/painokilo tai 0,1 umol/painokilo. Tällaisia  dieettejä  syötettiin 6kk  -12 kk.
Siitten apinoista  tutkittiin tumakalvot,  myeliini, mitokondriakalvot ja neuronien plasmakalvot ja seuraavat aivojen osat:  prefrontaalinen kuorikerros, pikkuaivot,   striatum ( kuorikerroken allaoleva harmaa tumake)  ja hippocampus. Mitattiin karotenoidit,  monityydyttämättömät rasvahapot (PUFA)   ja niitten oksidaatiotuotteet.
  • Adult rhesus monkeys were fed a stock diet (~2 mg/day lutein or ~0.5 μmol/kg body weight/day) (n = 9) or the stock diet plus a daily supplement of lutein (~4.5 mg/day or~1 μmol/kg body weight/day) and zeaxanthin (~0.5 mg/day or 0.1 μmol/kg body weight/day) for 6-12 months (n = 4).   Nuclear, myelin, mitochondrial, and neuronal plasma membranes were isolated using a Ficoll density gradient from prefrontal cortex (PFC), cerebellum (CER), striatum (ST), and hippocampus (HC). Carotenoids, PUFAs, and PUFA oxidation products were measured using HPLC, GC, and LC-GC/MS, respectively.
 Kaikista tutkituista  etuaivonkuoren   ja aivokuoren kalvoista  havaittiin all-trans-luteiinia (ng/mg proteiinia) ja se vaihteli suuresti eri yksilöiden kesken. Luteiini/zeaxantiinilisä  nosti merkitsevästi seerumin luteiinia sekä luteiinipitoisuuksia  etuaivojen ja kuorikerroksen  sekä mitokondrian kalvoissa, samoin kokonais DHA:n pitoisuus etuaivoissa kohosi . Etuaivoissa ja  striatumissa mitokondriaalinen  luteiini suhtautui käänteisesti DHA oksidaatiotuotteisiin, mutta ei arakidonihapon oksidaatiotuoteisiin. 

Mitä tästä pääteltiin ? Tieto on uutta subsellulaarisen  luteiinin kertymisestä ja sen suhteesta DHA rasvahappoon kädellisaivoissa.  Nämä löydöt  tukevat hypoteesia luteiinin osallistumsiesta  aivojen antioksidatiiviseen funktioon.

  • All-trans-lutein (ng/mg protein) was detected in all regions and membranes and was highly variable among monkeys. Lutein/zeaxanthin supplementation significantly increased total concentrations of lutein in serum, PFC and CER, as well as lutein in mitochondrial membranes and total DHA concentrations in PFC only (P<0 .05="" acid="" and="" arachidonic="" but="" dha="" from="" in="" inversely="" li="" lutein="" mitochondrial="" not="" oxidation="" pfc="" products="" related="" st="" those="" to="" was="">
  • This study provides novel data on subcellular lutein accumulation and its relationship to DHA oxidation in primate brain. These findings support the hypothesis that lutein may be associated with antioxidant functions in the brain.
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tisdag 20 februari 2018

Dokosanoidit ja niiden yleiskartta

Wikipediasta löydän tosiaan paljon dokosanoideista. Ensimmäisen kerran luin sellaisestakin rasvahappojohdannaisesta kuin resolviinit ja maresiinit suomalaisesta lähteestä Tohtori Tolonen ja  pidin aluksi  vähän epätodellisena, mutta aloin penkoa näitä karttoja esiin varmuuden vuoksi ja tulee molekyyliä kuin turkin hihasta ja kokonainen dokosanoidien uusi kartta vähitellen esiin. Nimittäin niiden  maineella jo  myydään valmisteita ja  kehutaan vaikutuksia.  Täytyy katsoa, voisivatko  ne  olla olemassa.  Sen lisäksi, että kaikista voi piirtää  oletettuja  kaavoja, pitää löytää myös artikkeleita joissa niitä tieteellisesti osoitetaan ja niiden oma vaikutus jollain tavalla voidaan erottaa muun  rasvakimpun vaikutuksista.  Siis nyt vain koetan hahmottaa karttaa.  Suomennan myös  tekstiä samalla ( välillä  vain omaan vihkooni)

Wikipediasta:
 Biokemiassa dokosanoidit ovat signaloinneissa vaikuttavia molekyylejä ja rakenteeltaan ne ovat 22 hiiltä sisältäviä rasvahappoja. Docosa tarkoittaa 22.  Ne ovat ensin tunnettu essentielleihin  rasvahappohin (EFA)  kuuluvasta  pitkästä omega3- rasvahaposta DHA, dokosahexaeenihappo.  Nimessä on hexa- sen takia että niissä  on 6 kaksoissidosta (hexa= 6).  Kaksoissidoksen paikat voidaan merkata Z kirjaimella  Esim. 4Z, 7Z, 10Z, 13Z, 16Z,19Z-dokosahexaeenihappo.  Z ei määritä  onko kyseessä R vai S isomeria.  Tästä  DHA-haposta voi tulla erilaisia dokosanoideja entsyymeillä (lipoxygenaasilla  LOX, syklo-oxygenaasilla  COX ja  sytokromi P450- entsyymeillä)
  1. From Wikipedia, the free encyclopedia
    In biochemistry, docosanoids are signaling molecules made by the metabolism of twenty-two-carbon fatty acids (EFAs), especially the omega-3 fatty acid, Docosahexaenoic acid (DHA) (i.e. 4Z,7Z,10Z,13Z,16Z,19Z-docosahexaenoic acid) by lipoxygenase, cyclooxygenase, and cytochrome P450 enzymes.

    Muista dokosanoideista  ( 22 hiilen PUFA- rasvahapoista):
     Omega 6 -sarjassa on pidentynyt (elongoitunut)  AA: Sen nimeksi voi asettaa
    DTA, dokosatetraeenihappo  ( 4 kaksoissidosta,7Z,10Z,13Z,16Z-dokosatetraeenihappo , adreenihappo)
    Jos  DTA lisäksi desaturoituu, tulee myös omega6- sarjasta DHA, dokosahexaeenihappolaji.
    Omega-3 sarjassa on   pidentynyt EPA ja sen nnimeksi voi laittaa   DPA  dokosapentaeenihappo ( viisi kaksoissidosta) (i.e. 7Z,10Z,13Z,16Z,19Z-dokosapentaeenihappo. Tämän pidentymä (+2C) tekee  tunnetun DHA hapon  omega3 sarjassa. 
     Sekä omega3 että omega 6-linjojen  dokosahexaeenihapoista  tulee vaikuttavia  välittäjäaineita , proresolviinien  luokka,   "proresolvin mediator class of  PUFA metabolites", sanotaan Wikipediassa) Tästä on lähdeartikkelia  linkissä ( specialized proresolving mediators).
     Tämä Wikipedia-artikkeli sisältää  huomattavista dokosanoideista tekstiä.  Asetan sen tällaisenaan  sitaatiksi nyt aluksi suomentamatta ja tarkistamatta vielä.  Se on netistä suoraan.

    Contents

    Prominent docosanoids

    Specialized proresolving mediator docosanoids

    Potently bioactive agents of the specialized proresolving mediator class include:
    These DHA metabolites possess anti-inflammation and tissue-protection activities in animal models of inflammatory diseases; they are proposed to inhibit innate immune responses and thereby to protect from and to resolve a wide range of inflammatory responses in animals and humans. These metabolites are also proposed to contribute to the anti-inflammatory and other beneficial effects of dietary omega-3 fatty acids by being metabolized to them.[1][2][3][4]

    Neurofuran docosanoids

    DHA can be converted non-enzymatically by free radical-mediated peroxidation to 8 different neurofuran regioisomers termed neuroprostanes and neurofuranes including 4-, 7-, 10-, 11-, 13-, 14-, 17-, and 20-series neurofurans/neuroporstanes for a total of 128 different racemic compounds. The most studied DHA-derived of these products are members of the 4-series, neurofuran 4-Fαneuroprostane and 4(RS)-ST-Δ6-8-neurofurane. These metabolites have been used mainly as biomarkers of oxidative stress that are formed in nerve tissues of the central nervous system.[5][6]

    Hydroxy-docosanoids (HpDHAs, HDHAs )

    Cells metabolize DHA to 17S-hydroperoxy-4Z,7Z,10Z,13Z,15E,19Z-docahexaenoicacid acid (17-HpDHA) and then rapidly reduce this hydroperoxide to 17S-hydroxy-4Z,7Z,10Z,13Z,15E,19Z-docahexaenoicacid acid (17-HDHA) and similarly metabolize DHA to 13S-hydroperoxy-4Z,7Z,10Z,14Z,16Z,19Z-docahexaenoic acid (13-HpDHA) and then to 13S-hydroxy-4Z,7Z,10Z,14Z,16Z,19Z-docahexaenoicacid acid (13-HDHA). 17-HDHA exhibits potent in vitro as well as in vivo (animal model) anti-inflammatory activity while 17-HpDHA and to a lesser extent 17-HDHA inhibit the growth of cultured human breast cancer cells.[7][8] Other SPM docosanoids, e.g. RvD1 and RvD2, have anti-growth effects against cancer cells in animal models.[9]

    Oxo-docosanoids  (EFOXD6s)

    Cells can metabolize DHA to products that possess an oxo (i.e. ketone) residue. These products include 13-oxo-DHA (termed EFOXD6) and 17-oxo-DHA (termed 18-EFOXD6). Both oxo metabolites possess anti-inflammatory activity as assesses in in vitro systems (see Specialized proresolving mediators#Oxo-DHA and oxo-DPA metabolites).[10]

    DTA-derived docosanoids (DH-EETs)

    Cyclooxygenase and Cytochrome P450 oxidase act upon Docosatetraenoic acid to produce dihomoprostaglandins[11] and dihomo-epoxyeicosatrienoic acids[12] and dihomo-EETs.[13]

    References

    Oily fish are a rich source of the DHA from which Docosanoids derive
  2. Calder PC (2015). "Marine omega-3 fatty acids and inflammatory processes: Effects, mechanisms and clinical relevance". Biochimica et Biophysica Acta. 1851 (4): 469–84. doi:10.1016/j.bbalip.2014.08.010. PMID 25149823.
  3. Serhan CN, Chiang N, Dalli J, Levy BD (2015). "Lipid mediators in the resolution of inflammation". Cold Spring Harbor Perspectives in Biology. 7 (2): a016311. doi:10.1101/cshperspect.a016311. PMID 25359497.
  4. Barden AE, Mas E, Mori TA (2016). "n-3 Fatty acid supplementation and proresolving mediators of inflammation". Current Opinion in Lipidology. 27 (1): 26–32. doi:10.1097/MOL.0000000000000262. PMID 26655290.
  5. Balas L, Durand T (2016). "Dihydroxylated E,E,Z-docosatrienes. An overview of their synthesis and biological significance". Progress in Lipid Research. 61: 1–18. doi:10.1016/j.plipres.2015.10.002. PMID 26545300.
  6. Arneson KO, Roberts LJ (2007). "Measurement of products of docosahexaenoic acid peroxidation, neuroprostanes, and neurofurans". Methods in Enzymology. 433: 127–43. doi:10.1016/S0076-6879(07)33007-3. PMID 17954232.
  7. Leung KS, Galano JM, Durand T, Lee JC (2015). "Current development in non-enzymatic lipid peroxidation products, isoprostanoids and isofuranoids, in novel biological samples". Free Radical Research. 49 (7): 816–26. doi:10.3109/10715762.2014.960867. PMID 25184341.
  8. Chiu CY, Gomolka B, Dierkes C, Huang NR, Schroeder M, Purschke M, Manstein D, Dangi B, Weylandt KH (2012). "Omega-6 docosapentaenoic acid-derived resolvins and 17-hydroxydocosahexaenoic acid modulate macrophage function and alleviate experimental colitis". Inflammation Research. 61 (9): 967–76. doi:10.1007/s00011-012-0489-8. PMID 22618200.
  9. O'Flaherty JT, Hu Y, Wooten RE, Horita DA, Samuel MP, Thomas MJ, Sun H, Edwards IJ (2012). "15-lipoxygenase metabolites of docosahexaenoic acid inhibit prostate cancer cell proliferation and survival". PLOS ONE. 7 (9): e45480. doi:10.1371/journal.pone.0045480. PMC 3447860 Freely accessible. PMID 23029040.
  10. Serhan CN, Chiang N, Dalli J (2015). "The resolution code of acute inflammation: Novel pro-resolving lipid mediators in resolution". Seminars in Immunology. 27 (3): 200–15. doi:10.1016/j.smim.2015.03.004. PMC 4515371 Freely accessible. PMID 25857211.
  11. Weylandt KH (2015). "Docosapentaenoic acid derived metabolites and mediators - The new world of lipid mediator medicine in a nutshell". European Journal of Pharmacology. doi:10.1016/j.ejphar.2015.11.002. PMID 2654672
  12. Campbell WB, Falck JR, Okita JR, Johnson AR, Callahan KS (1985). "Synthesis of dihomoprostaglandins from adrenic acid (7,10,13,16-docosatetraenoic acid) by human endothelial cells". Biochim. Biophys. Acta. 837 (1): 67–76. doi:10.1016/0005-2760(85)90086-4. PMID 3931686.
  13. Kopf PG, Zhang DX, Gauthier KM, Nithipatikom K, Yi XY, Falck JR, Campbell WB (2010). "Adrenic acid metabolites as endogenous endothelium-derived and zona glomerulosa-derived hyperpolarizing factors". Hypertension. 55 (2): 547–54. doi:10.1161/HYPERTENSIONAHA.109.144147. PMC 2819927 Freely accessible. PMID 20038752.
    14. Yi XY, Gauthier KM, Cui L, Nithipatikom K, Falck JR, Campbell WB (May 2007). "Metabolism of adrenic acid to vasodilatory 1alpha,1beta-dihomo-epoxyeicosatrienoic acids by bovine coronary arteries". Am J Physiol Heart Circ Physiol. 292 (5): H2265–74. doi:10.1152/ajpheart.00947.2006. PMID 17209008
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Päivän löytönä adreenihappo, ("pidentynyt AA"), C22:4 omega6.

http://hyper.ahajournals.org/content/55/2/547
otan tästä sitaatin.  katsahdin artikkelia etsiessäni karttaa diHETE molekyyleist ja löysin kartn  C22:4 omega molekyyleistä ja luulin ensin virheeksi koska se oli yhtä laaja kuin C-20:4 omega 6 kartta.  Muta niin se vain on että se on laaja kartta.  Tämä löytöhappo  voi betaoksidoitua kyllä takaisin arakidonihapoksi,  jonka  elongoituma se on. Onhan se ollut tietty n-6  kartassani jo aikaa, mutta sen merkitys ei ole ollut  tiedossani. 

SITAATTI
Prostaglandins, Arachadonic Acid Metabolites

Adrenic Acid Metabolites as Endogenous Endothelium-Derived and Zona Glomerulosa-Derived Hyperpolarizing Factors

Phillip G. Kopf, David X. Zhang, Kathryn M. Gauthier, Kasem Nithipatikom, Xiu-Yu Yi, John R. Falck, William B. Campbell
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https://doi.org/10.1161/HYPERTENSIONAHA.109.144147
Hypertension. 2010;55:547-554
Originally published January 20, 2010

Abstract

Adrenic acid (docosatetraenoic acid), an abundant fatty acid in the adrenal gland, is identical to arachidonic acid except for 2 additional carbons on the carboxyl end. Adrenic acid is metabolized by cyclooxygenases (COXs), cytochrome P450s, and lipoxygenases (LOXs); however, little is known regarding the role of adrenic acid and its metabolites in vascular tone. Because of its abundance in the adrenal gland, we investigated the role of adrenic acid in vascular tone of bovine adrenal cortical arteries and its metabolism by bovine adrenal zona glomerulosa cells. In adrenal cortical arteries, adrenic acid caused concentration-dependent relaxations, which were inhibited by the epoxyeicosatrienoic acid (EET-)antagonist 14,15-epoxyeicosa-5(Z)-enoic acid and the cytochrome P450 inhibitor SKF-525A. The large-conductance calcium-activated potassium channel blocker iberiotoxin or removal of the endothelium abolished these relaxations. Reverse-phase high-pressure liquid chromatography and liquid chromatography/mass spectrometry isolated and identified numerous adrenic acid metabolites from zona glomerulosa cells, including dihomo-epoxyeicosatrienoic acids and dihomo-prostaglandins. In denuded adrenal cortical arteries, adrenic acid caused concentration-dependent relaxations in the presence of zona glomerulosa cells but not in their absence. These relaxations were inhibited by SKF-525A, 14,15-epoxyeicosa-5(Z)-enoic acid, and iberiotoxin. Dihomo-16,17-epoxyeicosatrienoic acid caused concentration-dependent relaxations of adrenal cortical arteries, which were inhibited by 14,15-epoxyeicosa-5(Z)-enoic acid and high potassium. Our results suggest that adrenic acid relaxations of bovine adrenal cortical arteries are mediated by endothelial and zona glomerulosa cell cytochrome P450 metabolites. Thus, adrenic acid metabolites could function as endogenous endothelium-derived and zona glomerulosa-derived hyperpolarizing factors in the adrenal cortex and contribute to the regulation of adrenal blood flow.


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