GSR (8p12) on eräs antioksidanttijärjestelmän entsyymi. Miten se säätynee?

(GR entsyymit tunnen K-vitamiinisyklistä)
Miten tämä  liittyy kelch-proteiinien happihomeostaasia ja  happiradikaali-xenobioottihallintaa suorittaviin  sykleihin.  Mistä löytyy yhteisiä nimittäjiä?

https://www.ncbi.nlm.nih.gov/gene/2936

Official Full Name

glutathione-disulfide reductaseprovided by HGNC

Also known as

GR; GSRD; HEL-75; HEL-S-122m

Summary

This gene encodes a member of the class-I pyridine nucleotide-disulfide oxidoreductase family. This enzyme is a homodimeric flavoprotein. It is a central enzyme of cellular antioxidant defense, and reduces oxidized glutathione disulfide (GSSG) to the sulfhydryl form GSH, which is an important cellular antioxidant. Rare mutations in this gene result in hereditary glutathione reductase deficiency. Multiple alternatively spliced transcript variants encoding different isoforms have been found. [provided by RefSeq, Aug 2010]

Expression Ubiquitous expression in colon (RPKM 26.7), kidney (RPKM 25.9) and 25 other tissues See more Orthologs mouse all

 

1. Glutathione reductase mediates drug resistance in glioblastoma cells by regulating redox homeostasis. Zhu Z, et al. J Neurochem, 2018 Jan. PMID 29105080
2. Variable association of reactive intermediate genes with systemic lupus erythematosus in populations with different African ancestry. Ramos PS, et al. J Rheumatol, 2013 Jun. PMID 23637325, Free PMC Article
3. Expression of glutathione reductase splice variants in human tissues. Satoh N, et al. Biochem Genet, 2010 Oct. PMID 20628807
4. Age-dependent denaturation of enzymes in the human lens: a paradigm for organismic aging? Zhu X, et al. Rejuvenation Res, 2010 Oct. PMID 20586645
5. Inherited glutathione reductase deficiency and Plasmodium falciparum malaria--a case study. Gallo V, et al. PLoS One, 2009 Oct 6. PMID 19806191, Free PMC Article

See all (84) citations in PubMed

See citations in PubMed for homologs of this gene provided by HomoloGene

GeneRIFs: Gene References Into Functions

1. It has been shown that acute aerobic exercise activates Nrf2 in young men, irrespective of training intensity, but that high-intensity exercise demonstrated a greater effect on increasing glutathione reductase activity which could indicate improved redox potential. (Nrf2 säätyy kelch-proteeiini KEAP1-Nrf2  akselilla ja vastaa akuuttiin o0ksidatiiviseen  ja elektrofiiliseen stressiin)
   Abstract
   

   INTRODUCTION:
   The transcription factor Nrf2 is the master regulator of antioxidant defence. Recent data indicate a single bout of moderate-intensity stationary cycling at a constant workload upregulates Nrf2 signalling in young, but not older men; however, the role of exercise intensity on Nrf2 activation has not been tested. We hypothesised that a high-intensity interval session would elicit a greater Nrf2 response than moderate aerobic exercise. METHODS:
   Nrf2 signalling in response to two 30-min cycling protocols (high-intensity interval and constant workload) was compared in young men (25 ± 1y, n = 16). Participants completed exercise trials in random order with blood collected pre-, immediately post-, and 30-mins post exercise. Five participants completed a control trial without any physical activity. Nrf2 signalling was determined by measuring protein expression of Nrf2 in whole cell and nuclear fractions. Plasma 8-isoprostanes as well as peripheral mononuclear cell glutathione reductase (GR) and superoxide dismutase(SOD) activity were measured as markers of oxidative stress. RESULTS:
   The exercise trials elicited significant increases in nuclear Nrf2 (p < .01), but increases in whole cell Nrf2 did not reach statistical significance. GR activity and plasma 8-isoprostanes increased significantly in response to exercise (p < .05), and GR response was higher in the high-intensity trial (p < .05). CONCLUSION:
   Our findings indicate that acute aerobic exercise elicits activation of nuclear Nrf2, regardless of exercise intensity, but that higher-intensity exercise results in greater activity of GR. Future experiments should explore the effect of exercise mode and duration on Nrf2 signalling, and the role of intensity in compromised populations. KEYWORDS:
   8-isoprostanes; NFE2L2; Redox balance; aerobic exercise; glutathione reductase; interval training PMID: 28693341
    ( Tiedetään että ox stressi vaikuttaa Keap1/Nrf2 kompleksiin siten, että Nrf2 irtoaa tuosta degradatioon johtavasta  akselista ja alkaa kumuloitua tumaan. Se  vaikuttaa   kohdegeenien  transkriptiota ja myös sen omaa mRNA NRF2:ta muodostuu, mutta tumamatrixissa on toinen kelch-proteiini (KLHL37 muistaakseni), joka säätää alas tuman NRF2 ja mRNA NRF2, joten on ymmärrettävää, että sytoplasminen NRF ja totaali NRF2 ei kohoa vaan  NRF2:n kohdegeenistä, joka mahdollisesti GR on,  havaitaan kohonneita pitoisuuksia.  En tosin tiedä kuuluuko GR sen  lukuisiin kohdegeeneihin. Muistiin 2.12. 2019. Siis tämä toimii nuorilla parhaiten).

   DOI: 10.1080/10715762.2017.1353689

2. GSR expression was higher in TMZ-resistant cells than in sensitive cells. GSR silencing in drug-resistant cells improved the sensitivity of cells to TMZ or cisplatin. Over-expression resulted in resistance. GSR partially prevented the oxidative stress caused by L-buthionine -sulfoximine. The action of GSR in drug resistance is associated with the modulation of redox homeostasis. High GSR correlated with lower survival.
3. Plasma glutathione reductase (GR) activity was correlated with erythrocyte GR activity and the erythrocyte reduced glutathione/glutathione disulfide ratio. A decrease in plasma GR activity was associated with an increase in mortality in septic shock. ( Siis:  Tämän GR- entsyymin  esiintymisen aikaansaaminen  merkitsee  parempaa vastustuskykyä  septistä shokkia vastaan, On mahdollista mielestäni että K-vitmaiinisyklissä ilmenevä  nukleofiilinen reaktio ja epoksimuoto voivat  stimuloida Nrf2-esiintymistä ja täten myös GR- järjestelmän toimimista   K1 aktiivin  reduktiomuodon palauttamisessa. K1-vitamiinin saannilla on merkitystä  päivittäin tämän järjestelmän ylläpidossa. Päivittäinen tarve on  samaa luokkaa kuin päivittäinen menetys K1 vitamiini ei kerry elimistöön, koska se on xenobiootti-  sen tuma on  kehosta eritettävää metyylilnaftokinonia-  ja  niin se antanee tätä   Nrf2:lle tarvittavaa xenobioottista  virikettä   antioksidanttijärjestelmän  toimintaan).  En ole nähnyt kaavaa, jossa sen osuus liitetään Kelch-proteiinien osuuksiin. 2.12. 2019).    https://pubs.acs.org/doi/pdf/10.1021/acs.jafc.8b00866
4. Glutathione reductase reduces mitochondrial protein mitoNEET [2Fe-2S] clusters.
5. The recurrence of benign tumors of mammary gland occurred predominantly in women-carriers of mutant alleles with polymorphism rs8190924 of gene GSR and AA rs3763511of gene DKK4.
6. GSR was the most significant single SNP association with systemic lupus erythematosus in African Americans.
7. 1,25 (OH) vitamin D significantly upregulated expression of GCLC and GR and lowered secretion of IL-8 and MCP-1 in high-glucose exposed U937 monocytes.
8. The results demonstrate for the first time that glutathione reductase gene polymorphisms are significantly associated with bone mineral density.
9. Up-regulation of CAT and GR activity resulted in an increase in total antioxidant activity in A549 after exposure to B(a)P.
10. Human eye lenses were dissected into discrete regions that were formed at different stages of life and assayed for activity of lactate dehydrogenase (LDH) and a particularly stable enzyme, glutathione reductase (GR).