OXER1 reseptorista tietoja

Tietoja OXER1 reseptorista PubMed hakulaiteella   tietueesta :  

 https://www.ncbi.nlm.nih.gov/pubmed?term=OXER1&cmd=DetailsSearch

Otan yhden  artikkelin sitaattina: Siitä käy ilmi että OXER1 -reseptoriin vastavaikuttaa omega3-linjasta tuleva DHA*, dokosahexaeenihappo eli kalarasvoissa oleva pitkäketjuinen rasvahappo. Merkkaan tähdellä tämän lauseen:

 

 

Mol Cell Endocrinol. 2013 May 22;371(1-2):71-8. doi: 10.1016/j.mce.2012.11.003. Epub 2012 Nov 16.

Expression and function of OXE receptor, an eicosanoid receptor, in steroidogenic cells.

Cooke M¹, Di Cónsoli H, Maloberti P, Cornejo Maciel F.

Abstract

Hormonal regulation of steroidogenesis involves arachidonic acid (AA) metabolism through the 5-lipoxygenase pathway. One of the products, 5-hydroperoxy-eicosatetraenoic acid (5-HpETE), acts as a modulator of the activity of the steroidogenic acute regulatory (StAR) protein promoter. Besides, an oxoeicosanoid receptor of the leukotriene receptor family named OXE-R is a membrane protein with high affinity and response to 5-HpETE, among other AA derivatives.

• The aim of our work was to elucidate whether this receptor may be involved in steroidogenesis. RT-PCR and western blot analysis demonstrated the presence of the mRNA and protein of the receptor in human H295R adrenocortical cells. The treatment of H295R or MA-10 cells (murine Leydig cell line) with 8Br-cAMP together with docosahexaenoic acid (DHA*, an antagonist of the receptor) partially reduced StAR induction and steroidogenesis. On the contrary, 5-oxo-ETE - the prototypical agonist, with higher affinity and potency on the receptor - increased cAMP-dependent steroid production, StAR mRNA and protein levels. These results lead us to conclude that AA might modulate StAR induction and steroidogenesis, at least in part, through 5-HpETE production and activation of a membrane receptor, such as the OXE-R.

PMID:

23159987

DOI:

10.1016/j.mce.2012.11.003

Mead haposta engl. tekstiä

 Mead acid is an omega-9 fatty acid, first characterized by James F. Mead.^[1] As with some other omega-9 polyunsaturated fatty acids, animals

Wikipedian englantilaisesta versiosta löytyy enemmänkin  matabolista kartata Meadin haposta  

yleensä syklo-oxygenaasientsyymit  otavat substraatikseen arakidonihapon kun oksidoivat tulehduksissa  siitä  vaikuttavia aineita,kuten  PGH2   prostaglandiinia H2. Meadin happo muistuttaa arakidonia sikäli että siinä on 20 hiiltä ja ainakin 3 kaksoissidosta, joten  se  tarjoaa sellaista rakennetta, jota entsyymi voi käyttää arakidonihapon puutteessa. Meadin happo voi konvertoitua leukotrieeneksi  LTC3 ja LTD3.

Myös entyymi 5-lipoxygenaasi  voi  modifioida  Meadin happoa ja tekee siitä 5-hydroxy-eikosatrieenihappoa (5-HETrE). 

Entsyymi 5-hydroxyeikosanoididehydrogenaasi voi muuttaa sen sitten  5-oxoeikosatrieenihapoksi (5-oxo-ETrE). Tämä  metaboliitti taas on yhtä  vahva vaikuttaja  kuin sen arakidonihaposta tullut analogi  5-oxoeikosatetraeenihappo (5-oxo-ETE). Tässä vertaillaan niiden vaikutusta  stimuloida ihmisen veren eosinofiilejä ja neutrofiilejä. On ilmeistä että  Meadin haposta tuleva  15-oxo-ETrE käyttää  samaa reseptoria kuin arakidonihaposta tuleva analogi: nimittäin reseptoria OXER1  ja ehkä sen takia se on  kuin   analoginsa , ihmisen allergisten ja inflammatoristen reaktioiden  välittäjä.

Role in inflammation

Cyclooxygenases are enzymes known to play a large role in inflammatory processes through oxidation of unsaturated fatty acids. Most notably, the formation of prostaglandin H2 from arachidonic acid which is very similar in structure to mead acid. When physiological levels of arachidonic acid are low, other unsaturated fatty acids including mead and linoleic acid are oxidized by COX.
Mead acid is also converted to leukotrienes C3 and D3.^[8]
Mead acid is metabolized by 5-lipoxygenase to 5-hydroxyeicosatrieonic acid (5-HETrE)^[9] and then by 5-Hydroxyeicosanoid dehydrogenase to 5-oxoeicosatrienoic acid (5-oxo-ETrE).^[10] 5-Oxo-ETrE is as potent as its arachidonic acid-derived analog, 5-oxo-eicosatetraenoic acid (5-oxo-ETE), in stimulating human blood eosinophils and neutrophils;^[11] it presumably does so by binding to the 5-oxo-ETE receptor (OXER1) and therefore may be, like 5-oxo-ETE, a mediator of human allergic and inflammatory reactions

• Tietoja OXER1 reseptorista.

 https://en.wikipedia.org/wiki/Oxoeicosanoid_receptor_1

OXER1-reseptorin sijainti on kromosomissa 2p21.  Se on g-proteiiniin kytkeytynyt rseptori 170 (GPR170)  ja se on pääasiassa arakidonihaposta johtuvan karboksyylihappometaboliitin  5-HETEpääasiallinen reseptori.
Mielenkiintoinen kappale! Kuitenkin lopuksi sanotaan että tiedot ovat  toistaiseksi prekliinisiä.

 Oxoeicosanoid receptor 1 (OXER1) also known as G-protein coupled receptor 170 (GPR170) is a protein that in humans is encoded by the OXER1 gene located on human chromosome 2p21; it is the principle receptor for the 5-Hydroxyicosatetraenoic acid family of carboxy fatty acid metabolites derived from arachidonic acid.^[3][4][5] The receptor has also been termed hGPCR48, HGPCR48, and R527 but OXER1 is now its preferred designation


 To date, however, all studies have been pre-clinical; they use model systems that can suggest but not prove the contribution of OXER1 to human physiology and diseases. The most well-studied and promising area for OXER1 function is in allergic reactions. The recent development of OXER1 antagonists will help address this issue.

Omega9-linjasta Meadin happo

https://fi.wikipedia.org/wiki/Meadin_happo

Meadin happo eli (5Z,8Z,11Z)-eikosa-5,8,11-trieenihappo eli 20:3(n-9) on monityydyttymätön omega-9-rasvahappo, jonka kemiallinen kaava on C₂₀H₃₄O₂, moolimassa 306,48276 g/mol ja CAS-numero 20590-32-3.
Yhdiste on saanut nimensä James F. Meadin mukaan. Meadin happoa syntyy oleiinihapon reagoidessa nisäkkäiden aineenvaihdunnassa ja sitä on löydetty verestä ja rustosta. Meadin happoa käytetään C3 ja D3 leukotrieenien aiheuttaman tulehdusten pilkkomiseen.

Aiheesta muualla kts linkit.

Kommenttini: Katso kuvaa: 

Kuten huomaa, rasvahapon "häntäosa" on pidempi kuin omega6 ja omega3 sarjassa. Se onkin  omega9 sarjaa, eli siinä on 9 hiiliatomia ennen kuin tulee kaksoissidoksista ensimmäinen  päädystä lukien.  Oliviöljyä käytettäessä  siinä olevasta öljyhaposta  C18:1(n-9),    muodostuu tällaista  desaturaasi- ja elongaasientyymeillä kehossa. 

Ensin18:2 (n-9); 
sitten 20:2 (n-9),
sitten 20:3 (n-9), 
sitten 22:3 (n-9).  

 Ne entsyymit jotka muokkaavat n-6 ja n-3 sarjasta aineenvaihdunnallisia  tuotteita kuten leukotrieenejä (voivat muodostaa tästä  20:3 (n-9) kokoisesta metaboliitista LT3  leukotrieeniä.  (omega6 sarjan leukotrieenit ovat LT4- sarjaa ja omega-3 sarjasta tulevat leukotrieenit LT5-sarjaa).  Tiedetään että LT4 sarjasta tulee kliinisesrti aggressiivisia leukotrieenejä LT4 lajeja  ( 20 hiilen eikosanoideja) .  Nämä  n9- ja n3 sarjan leukotrieenit LT3 ja LT5  voivat voivat tehdä interaktiota  sen aggressiivisuuteen ja niillä voi olla joitain aivan omia vaikutuksiaan, kun niitä vain löytää kirjallisuudesta. 

Henkilökohtaisesti olen nyt kiinnostunut  siitä, miten tämän 9n-sarjan tuotteet  degradoituvat.

 

• PubChem: Mead acid (englanniksi)
• Human Metabolome Database: 5,8,11-Eicosatrienoic acid (englanniksi) 
• 
  

Rasvametaboliittien osuus syövässä

http://www.aimspress.com/article/10.3934/genet.2017.2.103/fulltext.html

DNA damage by lipid peroxidation products: implications in cancer, inflammation and autoimmunity

Fabrizio Gentile¹, Alessia Arcaro¹, Stefania Pizzimenti², Martina Daga², Giovanni Paolo Cetrangolo¹, Chiara Dianzani³, Alessio Lepore⁴, Maria Graf⁴, Paul R. J. Ames⁵, Giuseppina Barrera^{2, ,}

1 Department of Medicine and Health Sciences “V. Tiberio”, University of Molise, Campobasso, Italy
2 Department of Clinical and Biological Sciences, University of Torino, Torino, Italy
3 Department of Drug Science and Technology, University of Torino, Torino, Italy
4 Department of Molecular Medicine and Medical Biotechnologies, University of Naples Federico II, Naples, Italy
5 CEDOC, NOVA Medical School, Universidade NOVA de Lisboa, Lisboa, Portugal, and Department of Haematology, Dumfries Royal Infirmary, Dumfries, Scotland, UK 

• Otan talteen lyhennykset, koska  ne voivat antaa hakusanoja 

Abbreviations and symbols

AA: arachidonic acid, 5, 8, 11, 14-eicosatetraenoic acid   

ADHs: alcohol dehydrogenases

ALA: alpha-linolenic acid, 9, 12, 15-octadecatrienoic acid  

 ALDHs: Aldehyde dehydrogenases

ANA: antinuclear autoantibodies  

APCs: antigen-presenting cells

AR: aldose reductase  

 BSA: bovine serum albumin

1, N6-ε-dAde: 1, N6-etheno-2'-deoxyadenosine  

 dAde: deoxyadenosine

DAMPs: damage-associated molecular patterns  

DCs: dendritic cells

dCyt: deoxycytidine  

ε-dCyt: 3, N4-etheno-2'-deoxycytidine

N2-dGuo: N2-propano-2'-deoxyguanosine   

dGuo: deoxyguanosine

1, N2-ε-dGuo: 1, N2-etheno-2'-deoxyguanosine    

dsDNA, double-strand DNA

N2, 3-ε-dGuo: N2, 3-etheno-2'-deoxyguanosine    

EHN: 2, 3-epoxy-4-hydroxy-nonanal

DHA: 4, 7, 10, 13, 16, 19-docosahexanoic acid  

 GPX2: glutathione peroxidase 2

GAPDH: glyceraldehyde-3-phosphate dehydrogenase 

GSTs: glutathione-S-transferases

HCC: hepatocellular carcinoma   

HDAC: histone deacetylase

HDL3: high-density lipoprotein 3   

HHE: 4-hydroxy-2(E)-hexenal

HNE: 4-hydroxy-2-nonenal   

HPHE: 4-hydroperoxy-2(E)-hexenal

HPNE: 4-hydroperoxy-2(E)-nonenal    

HSA: human serum albumin

HSP60: heat shock 60 kDa protein 1   

HY-RNAs: histidine-rich RNAs

KLH: keyhole limpet hemocyanine  

LDLs: low-density lipoproteins

LA: linoleic acid, 9, 12-octadecadienoic acid

LMP1: latent membrane protein-1

LO·: alkoxyl radical   

LOO·: lipoperoxyl radical

LOX-1: oxidized low-density lipoprotein receptor 1  

LOOH: lipid hydroperoxide

LPO: lipid peroxidation   

 mAbs: monoclonal antibodies

MDA: malondialdehyde    

MSA: murine serum albumin

NAFLD: non-alcoholic fatty liver disease  

NASH: non-alcoholic steatohepatitis

Nrf2: NF-E2-related factor 2    

NZW: New Zealand White

8-OHdG: 8-hydroxydeoxyguanosine   

·OH: hydroxyl radical

OHE: 4-oxo-2(E)-heptenal    

ONE: 4-oxo-2(E)-nonenal

oxLDLs: oxidized low-density lipoproteins  

OSEs: oxidation-specific epitopes

PRRs: pattern recognition receptors  

 PUFAs: polyunsaturated fatty acids

RA: rheumatoid arthritis   

RLIP76: Ral-interacting protein

RNPs: ribonucleoprotein particles  

ROS: reactive oxygen species

SCE: sister chromatide exchange   

SLE: systemic lupus erythematosus

SOD2: superoxide dismutase 2   

SS: Sjögren syndrome

α-CH3-γ-OH-PdG: α-hmethyl-γ-hydroxy-1, N2-propano-2'-deoxyguanosine

HNE-dGuo: 1, N2-propano-2'-deoxyguanosine adduct of HNE

9(S)-HPODE: 9(S)-hydroperoxy-9, 11-octadecadienoic acid

13(S)-HPODE: 13(S)-hydroperoxy-9, 11-octadecadienoic acid

MAP kinases: mitogen-activated protein kinases

MCL1: induced myeloid leukemia cell differentiation protein Mcl-1

M1dA: N6-(3-oxoprenyl)-deoxyadenosine

M1dC: N4-(3-oxoprenyl)-deoxycytidine

M1dG: malondialdehyde-2'-deoxyguanosine, or pyrimido[1, 2-a]purine-10(3H)-one-2'-deoxyribose

α-OH-PdG: α-hydroxy-1, N2-propano-2'-deoxyguanosine

γ-OH-PdG: γ-hydroxy-1, N2-propano-2'-deoxyguanosine

ONE-dAde: 7-(2"-oxoheptyl)-1, N6-etheno-2'-deoxyadenosine

ONE-dCyt: 7-(2"-oxoheptyl)-3, N4-etheno-2'-deoxycytidine

ONE-dGuo: 7-(2"-oxoheptyl)-1, N2-etheno-2'-deoxyguanosine

OPdG: N2-(3-oxoprop-1-enyl)-deoxyguanosine

8-oxo-dGuo: 8-oxo-hydroxy-7, 8-dihydro-2'-deoxyguanosine

PdG: N2-(3-oxopropyl)-deoxyguanosine

PEITC: beta-phenylethyl isothiocyanate

PPAR gamma: peroxisome proliferator-activated receptor gamma

In recent years, it has become evident that lipid peroxidation (LPO) products are involved in the intracellular signaling mechanisms that determine the cell's final fate ^[1]. LPO arises from the oxidation of fatty acids induced by oxidative stress causing agents, e.g., oxidants, heat shock, UV and X irradiation, metal storage, excess caloric intake and serum starvation. Oxidative stress imports increases of reactive oxygen species (ROS) which, in turn, can affect signaling mechanisms in a concentration-dependent manner ^[2]. However, although increased ROS production has been observed in several human diseases, such as cancer and neurodegenerative diseases, an increase of LPO products is not always present. This is true in particular for cancer cells, which often display high levels of oxidative stress, whereas increased levels of LPO products were present only in some cancer types, depending on the lipid composition of cellular membranes, the presence of inflammation and the level of aldehyde metabolizing enzymes ^[3,4]. On the contrary, in inflammatory and neurodegenerative diseases the increases of ROS almost always were accompanied by increases of LPO and, as a consequence, LPO products.

Several studies have been performed regarding the biological roles played by aldehydes, since they have a prolonged half-life, can diffuse from their sites of formation and react with the surrounding cells. Moreover, the aldehydes can be delivered by the bloodstream and secreted in the urine. To the contrary, free radicals, produced during LPO, have a very short life and can produce only localized effects. For these reasons, the aldehydes have been defined as "second messengers of oxidative stress" ^[5]. These lipid electrophiles have long been studied, due to their potential to react with nucleophilic functional groups in lipids, proteins, and DNA ^[6]. The nucleophilic functional groups include sulfhydryl, guanidine, imidazole and amino groups and DNA bases. In particular, the aldehydes often attack the free-NH₂₋ groups of DNA bases to form covalent adducts, which are partially responsible for the biological consequences of LPO in normal physiology and pathophysiology. In this review we summarize the most recent evidence of DNA damage by LPO products in several diseases, such as cancer, inflammation and autoimmunity.

Rasvaisen dieetin vaikutus luustoon

 Tukevuus sinänsä ei ole niin paha asia, mutta painovakauden menetys on signaali jostain håiriötilasta  joka on progredioimassa johonkin suuntaan, arvelen. Ja siltä kannalta voi painon kasvu olla signaali esim  alkavasta syövästä. Tässä aksotaan mikä suhde  rasvaisella ravinnolla on luun muodostukseen. ei erityisempää korrelaatiota,.

LÄHDE: https://www.ncbi.nlm.nih.gov/pubmed/29188898

J Nutr Health Aging. 2017;21(10):1337-1343. doi: 10.1007/s12603-017-0871-x.

Influence of High-Fat Diet on Bone Tissue: An Experimental Study in Growing Rats.

Rezende Yanagihara G¹, Carminati Shimano R, Atsuko Tida J, Suzuki Yamanaka J, Yasuyo Fukada S, Mardegan Issa JP, Shimano AC, Tavares JM.

Abstract

BACKGROUND:
The relationship between obesity and bone tissue remains contradictory, especially when the effect of high-fat diet is assessed in experimental models. The aim of this study was to evaluate the effects of high-fat diet on bone metabolism of growing rats.
METHODS:
Twenty weaned female Wistar rats were equally divided into two groups: SD (standard diet) and HFD (high-fat diet with 60 % of energy as fat). After five weeks of the two diets, the rats were euthanized, and the liver, blood and bones extracted. The liver was analysed for malondialdehyde (MDA) and reduced glutathione (GSH) concentrations. Blood was analysed by the ELISA method for osteoprotegerin (OPG) and tumour necrosis factor ligand superfamily member 11 (TNFSF11/RANKL). The bone tissue was analysed by dual-energy X-ray absorptiometry (DXA), mechanical tests, computed microtomography, histological quantitative analysis and scanning electron microscopy. The gene expressions of PPAR-γ Runx-2, RANKL and Cathepsin-K were also evaluated.
RESULTS:
HFD caused an increase in the MDA concentration, indicating oxidative stress. It also increased the expression of PPAR-γ, which is the gene that is related to adipocyte differentiation. There was an increase in BMD of the tibia of animals fed with the HFD, but other microstructural and mechanical properties were maintained unaltered. In addition, there were no changes in the gene expressions related to the differentiation of osteoblasts and osteoclasts, as well as no changes to the biochemical markers of bone formation and bone resorption.
CONCLUSION:
Liver and gene parameters are changed in response to the HFD. However, although there was an increase in BMD, the microstructure and function of the bone did not change after a 5-week HFD.

KEYWORDS:
Bone mineral density; bone quality; obesity; osteoporosis

PMID:

29188898

DOI:

10.1007/s12603-017-0871-x

Tieto malondialdehydistä 1986 eläinkokeista

https://www.ncbi.nlm.nih.gov/pubmed/3713450
1. Tiedetään että lipidiperoksidaatio tuottaa MDA:ta jo dieetin puolella ja sitten kehossa.
2. Sillä on reaktiivisuutta  tumahappojen, proteiinien ja fosfolipidien  funktionaalisiin ryhmiin,
3. Se on bakteerille mutageeninen.
4. Koe-eläimissä se on ihosyöpää ja maksasyöpää aiheuttava.
Artikkeli kuvaa eläinkokeita, joisa syötettiin  malondialdehydin natriumenolisuolaa.se vaikutti maksasolutumien  annoksesta riippuvia hyperplastisia ja neoplastisia muutoksia ja nosti mortaliteetin mitä korkeimmalle tasolle aiheutamatta kuitenkaan maksatuumoreita.
Ihofibroblastiviljelmään lisättynä se aiheutti epänormaaliutta tumiin.
(1,3,C14*)  -merkattu MDA oxidoitui (C14*) asetaatiksi  sekä  C*O2  hiilidioksidiksi  in vivo  nopeasti koeläimen maksan mitokondrioissa. Kuitenkin radioaktiivisuudesta oli havaittavissa 10% virtsasta.
Kromotagrafisesti havaittiin useita tuoteita, joista  tuli MDA:ta happohydrolyysissä.
MDA:n kokonaiseritys lisääntyi lipidiperoksidaatiota aiheuttavista seikoista, kuten E-vitamiinin puutteesta, raudasta, hiilitetrakloridista ja kudosten rikastamisesta PUFA-rasvahapoilla.
MDA:n päämetaboliittina virtsassa todettiin N-asetyl-e-(2-propenal)lysiiniä.
Kun MDA reagoi  ensisijaisesti ravinnossa tulevien  N-terminaalisten lysiinien epsilon-aminoryhmän kanssa,  muodostuu yllämainittua tuotetta. Mutta sitä muodsotuu myös kehossa, sillä jos koe-eläimiä pidettiin MDA-vapaalla dieetillä tai paastossa, niin tuota molekyyliä  esiintyi kuitenkin virtsassa.

Lipids. 1986 Apr;21(4):305-7.

The metabolism of malondialdehyde.

Draper HH, McGirr LG, Hadley M.

Abstract .Interest in malondialdehyde (MDA) metabolism stems from its formation as a product of lipid peroxidation in the diet and in the tissues; its reactivity with functional groups of nucleic acid bases, proteins and phospholipids; its mutagenicity in bacteria, and its reported skin and liver carcinogenicity in animals. 

Administration of the Na enol salt of MDA in the drinking water of mice over a range of 0.1-10.0 micrograms/g/day for 12 mo produced dose-dependent hyperplastic and neoplastic changes in liver nuclei and increased mortality at the highest level but produced no gross hepatic tumors.
Addition of MDA to the medium of rat skin fibroblasts grown in culture caused nuclear abnormalities at concentrations as low as 10(-6) M despite an uptake of only 4%.
[1,3-14C] MDA was rapidly oxidized to [14C]acetate in rat liver mitochondria and to 14CO2 in vivo; however, approximately 10% of the radioactivity was recovered in the urine.
Chromatographic analysis of rat urine revealed the presence of several compounds which yield MDA on acid hydrolysis.
Total MDA excretion increased in response to conditions which stimulate lipid peroxidation in vivo, including vitamin E deficiency, Fe or CCl4 administration, and enrichment of the tissues with PUFA.
N-acetyl-e-(2-propenal)lysine was identified as a major urinary metabolite of MDA in rat and human urine. This compound is derived primarily from N-alpha-(2-propenal)lysine released in digestion as a product of reactions between MDA and the epsilon-amino groups of N-terminal lysine residues in food proteins. However, its presence in the urine of animals fasted or fed MDA-free diets indicates that it is also formed in vivo.(ABSTRACT TRUNCATED AT 250 WORDS).

Suomennos 22.1. 2018
Kommentti: Käytännössä tämä merkannee sitä,että PUFA- käytöllä on jokin suositeltu ylärajansa joka  ehkä on individuelli.

ALDH1L2

Tämän toisen  ALDH:n  sijainti  genomissa  on Kr. 12q23.3. 

Entsyyminumero on EC 1.5.1.6.  Muita nimiä ovat MIFDH, mitokondriaalinen 10-formyl THFDH. Aldehyde dehydrogenase family 1 member L2, mitochondrial tämä tekee mitokondriassa samaa  esteraasifunktiota kuin ALDH1 sytosolinen eikä pysty  dehydrogenoimaan lyhytiä aldehydejä.  ( Siis tarvitaan ALDH2  niitä varten) .

ALDH1L1  sytosolinen on astrosyytille merkitsijämolekyylikin.Jos tämä puuttuu, solu ei pysty käsittelemään  ainenvaidhunnan muurahaishappoa ( formate), sillä muurahaishaposta JCOOH pitäisi tulla hiilidioksidia CO2 . Entsyymissä on f eli formyl-ryhmä  HCOO- 

Tein haun ALDH1L1 geenistä- pohdin, voiko  olla edes olemassa ihmisiä joilta tämä geeni puuttuu- ei kai.  Jos geeni tuote on heikentynyttä, tilanne  on vaikea, arvelen. Koetan etsioä jonkin lähteen. 

 Sain nämä kaksi vastausta.

Items: 2

Select item 264665631.

Oxidative stress inhibits distant metastasis by human melanoma cells.

Piskounova E, Agathocleous M, Murphy MM, Hu Z, Huddlestun SE, Zhao Z, Leitch AM, Johnson TM, DeBerardinis RJ, Morrison SJ.

Nature. 2015 Nov 12;527(7577):186-91. doi: 10.1038/nature15726. Epub 2015 Oct 14.

PMID:

26466563

Free PMC Article

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Select item 212384362.

Enzymatic properties of ALDH1L2, a mitochondrial 10-formyltetrahydrofolate dehydrogenase.

Strickland KC, Krupenko NI, Dubard ME, Hu CJ, Tsybovsky Y, Krupenko SA.

Chem Biol Interact. 2011 May 30;191(1-3):129-36. doi: 10.1016/j.cbi.2011.01.008. Epub 2011 Jan 14.

PMID:

21238436

Free PMC Article

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malondialdehydin entsymaattinen hajoaminen

 MDA  käyttää entsymaattiseen hajoamiseensa  ALDH entsyymiä.  ALDH2  on mitokondriaalinen ja sitä esiintyy eniten rasvakudoksissa ja maksassa, myös munuainen on kolmantena tässä luettelossa.

 Aldehydidehydrogenaasi ALDH  on  alkoholiaineenvaihdunanssa toinen tärkeä entsyymi oksidatiivisessa tiessä.
Sitä on  2 muotoa. Toinen on mitokondriaalinen ALDH2 ja toinen on sytosolinen.
Ihmiskunnan kaikilal heimoilla ei ole tätä maksan mitokondriaalista ALDH2 entsyymiä ja heillä on vain sytosolinen ALDHS kuten  etelä-Aasiassa. Käytännössä tämä merkitsee sitä, että näillä henkilöillä on vaikeampia  intoksikaatioita alkoholista.
Saan tästä amerikkalaislähteestä aivan eilen päivitettyä tietoa vaikka  tietokone  kertoo jostain  häiriöstä USA:n hallinnollisella  ekonomisella  taholla (  a lapse in governemental funding), joka on ylläpitänyt näitä tietopankkeja.   Näitä varoituksia  mahdollisten  tieteellisten päivitysten viivästymisestä  tuli jo eilen. No, sainhan onneksi  kaikki mitä olen etsinyt tietueesta eilen ja tänään.Lähinnä geeni ja kromosomitietoutta.  Nytkin olen etsimässä geenin sijaintia kromosomissa.

https://www.ncbi.nlm.nih.gov/gene/217

ALDH2 aldehyde dehydrogenase 2 family (mitochondrial) [ Homo sapiens (human) ]

Gene ID: 217, updated on 21-Jan-2018

Official Symbol

ALDH2provided by HGNC

Official Full Name

aldehyde dehydrogenase 2 family (mitochondrial)provided by HGNC

Primary source

HGNC:HGNC:404

See related

Ensembl:ENSG00000111275 MIM:100650; Vega:OTTHUMG00000169603

Gene type

protein coding

RefSeq status

REVIEWED

Organism

Homo sapiens

Lineage

Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo

Also known as

ALDM; ALDHI; ALDH-E2

Summary

This protein belongs to the aldehyde dehydrogenase family of proteins. Aldehyde dehydrogenase is the second enzyme of the major oxidative pathway of alcohol metabolism. Two major liver isoforms of aldehyde dehydrogenase, cytosolic and mitochondrial, can be distinguished by their electrophoretic mobilities, kinetic properties, and subcellular localizations. Most Caucasians have two major isozymes, while approximately 50% of East Asians have the cytosolic isozyme but not the mitochondrial isozyme. A remarkably higher frequency of acute alcohol intoxication among East Asians than among Caucasians could be related to the absence of a catalytically active form of the mitochondrial isozyme. The increased exposure to acetaldehyde in individuals with the catalytically inactive form may also confer greater susceptibility to many types of cancer. This gene encodes a mitochondrial isoform, which has a low Km for acetaldehydes, and is localized in mitochondrial matrix. Alternative splicing results in multiple transcript variants encoding distinct isoforms.[provided by RefSeq, Nov 2016]

Expression

Broad expression in fat (RPKM 510.6), liver (RPKM 492.8) and 19 other tissues See more

See ALDH2 in Genome Data Viewer Map Viewer

Location:

12q24.12

 

Koetan löytää ALDH1:stä  jotain teitoa.  Astrosyytin merkitsijöihin uetellaan myös ALDH1-perheen jäsen L1. https://www.ncbi.nlm.nih.gov/pubmed/28336567

Cilostazol

https://www.ncbi.nlm.nih.gov/pubmed/29264710

Cell Stress Chaperones. 2017 Dec 20. doi: 10.1007/s12192-017-0828-3. [Epub ahead of print]

Protective effects of cilostazol on ethanol-induced damage in primary cultured hepatocytes.

Xie X¹, Xu X², Sun C¹, Yu Z³.

Abstract

Alcoholic liver disease (ALD) caused by excessive alcohol consumption is associated with oxidative stress, mitochondrial dysfunction, and hepatocellular apoptosis. Cilostazol, a licensed clinical drug used to treat intermittent claudication, has been reported to act as a protective agent in a spectrum of diseases.
However, little information regarding its role in ethanol-induced hepatocellular toxicity has been reported. In the current study, we investigated the protective effects and mechanisms of cilostazol on ethanol-induced hepatocytic injury. Rat primary hepatocytes were pretreated with cilostazol prior to ethanol treatment. MTT and LDH assay indicated that ethanol-induced cell death was ameliorated by cilostazol in a dose-dependent manner. Our results display that overproduction of intracellular reactive oxygen species (ROS) and 4-hydroxy-2-nonenal (4-HNE) induced by ethanol was attenuated by pretreatment with cilostazol.
 Furthermore, cilostazol significantly inhibited ethanol-induced generation of ROS in mitochondria. Importantly, it was shown that cilostazol could improve mitochondrial function in primary hepatocytes by restoring the levels of ATP and mitochondrial membrane potential (MMP). Additionally, cilostazol was found to reduce apoptosis induced by ethanol using a terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) assay.
 Mechanistically, we found that cilostazol prevented mitochondrial pathway-mediated apoptotic signals by reversing the expression of Bax and Bcl2, the level of cleaved caspase-3, and attenuating cytochrome C release. These findings suggest the possibility of novel ALD therapies using cilostazol.

KEYWORDS:
Alcoholic liver disease; Apoptosis; Cilostazol; Ethanol; Mitochondria; Oxidative stress

PMID:

29264710

DOI:

10.1007/s12192-017-0828-3

Iskemia, MDA, 4-HNE, ALDH2 . Alfaliponihapon merkitys

https://www.ncbi.nlm.nih.gov/pubmed/22266491

Eur J Pharmacol. 2012 Mar 5;678(1-3):32-8. doi: 10.1016/j.ejphar.2011.12.042. Epub 2012 Jan 12.

Alpha lipoic acid protects heart against myocardial ischemia-reperfusion injury through a mechanism involving aldehyde dehydrogenase 2 activation.

He L¹, Liu B, Dai Z, Zhang HF, Zhang YS, Luo XJ, Ma QL, Peng J.
Abstract

Recent studies demonstrate that alpha lipoic acid can prevent nitroglycerin tolerance by restoring aldehyde dehydrogenase 2 (ALDH2) activity and ALDH2-mediated detoxification of aldehydes is thought as an endogenous mechanism against ischemia-reperfusion injury. This study was performed to explore whether the cardioprotective effect of alpha lipoic acid was related to activation of ALDH2 and the underlying mechanisms. In a Langendorff model of ischemia-reperfusion in rats, cardiac function, activities of creatine kinase (CK) and ALDH2, contents of 4-hydroxy-2-nonenal (4-HNE) and malondialdehyde (MDA) were measured. In a cell model of hypoxia-reoxygenation, the apoptosis, ALDH activity, reactive oxygen species level, 4-HNE and MDA contents were examined. In the isolated hearts, ischemia-reperfusion treatment led to cardiac dysfunction accompanied by an increase in 4-HNE and MDA contents. Pretreatment with lipoic acid significantly up-regulated myocardial ALDH2 activity concomitantly with an improvement of cardiac dysfunction and a decrease in 4-HNE and MDA contents, these effects were blocked by the inhibitor of ALDH2. Similarly, in the cultured cardiomyocytes, hypoxia-reoxygenation treatment induced apoptosis accompanied by an increase in the production of reactive oxygen species, 4-HNE and MDA. Administration of lipoic acid significantly up-regulated cellular ALDH2 activity concomitantly with a reduction in apoptosis, production of reactive oxygen species, 4-HNE and MDA, these effects were reversed in the presence of ALDH2 or PKCε inhibitors. Our results suggest that the cardioprotective effects of lipoic acid on ischemia-reperfusion injury are through a mechanism involving ALDH2 activation. The regulatory effect of lipoic acid on ALDH2 activity is dependent on PKCε signaling pathway.

PMID:

22266491

DOI:

10.1016/j.ejphar.2011.12.042

[Indexed for MEDLINE]

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