抗酸化酵素 スーパーオキシドディスムターゼ(SOD)

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活性酸素関連記事

 

概要

https://ja.wikipedia.org/wiki/スーパーオキシドディスムターゼ

SODは、スーパーオキシドアニオン(O2)を酸素と過酸化水素(H2O2)へ変換する酸化還元酵素。

銅イオンと亜鉛イオン(Cu, ZnSOD)、マンガンイオン(MnSOD)、鉄イオン(FeSOD)などの金属イオンを持った酵素。

細胞質(Cu, ZnSOD) やミトコンドリア(MnSOD)に多く局在している。

寿命と相関するSOD活性

酸素消費量の多さに対してSOD活性の強さは、寿命と相関があると言われている。

SOD1は、細胞液中 SOD3は細胞外に存在する。

SOD-2(MnSOD)

ミトコンドリア内に存在し、ミトコンドリアで産生されたスーパーオキシド(ーO2)を毒性の低い過酸化水素と酸素に変換。

トレードオフ関係にあるSOD量

癌細胞を死滅させるにはスーパーオキシドが必要なため、SOD2が過剰にありすぎると、腫瘍転移の増大につながる。

一方でSODの過剰生産は活性酸素であるスーパーオキシドを抑制し、ハエの寿命を20%増加させるなど、SODの生産量はトレードオフの関係にある。

「superoxide dismutase mnsod」の画像検索結果

Absence of manganese superoxide dismutase delays p53-induced tumor formation
Manganese superoxide dismutase (MnSOD) is a mitochondrial antioxidant enzyme that is down-regulated in a majority of cancers. Due to this observation,…
アミロイドβへの影響

SOD2の過剰発現は、アミロイド班の沈着を減少させ、ADマウスの記憶障害を改善する。

Overexpression of SOD-2 reduces hippocampal superoxide and prevents memory deficits in a mouse model of Alzheimer's disease. - PubMed - NCBI
Proc Natl Acad Sci U S A. 2009 Aug 11;106(32):13576-81. doi: 10.1073/pnas.0902714106. Epub 2009 Aug 3. Research Support, N.I.H., Extramural; Research Support, ...
Mitochondrial superoxide: a key player in Alzheimer's disease

MnSODノックアウトマウスでは、脳内のアミロイドβレベルおよびアミロイドβの負荷を有意に増加させる。

Increased plaque burden in brains of APP mutant MnSOD heterozygous knockout mice. - PubMed - NCBI
J Neurochem. 2004 Jun;89(5):1308-12. Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.

SOD2の欠損は、アミロイド負荷を悪化させ、リン酸化タウレベルを増加させる。

Mitochondrial oxidative stress causes hyperphosphorylation of tau. - PubMed - NCBI
PLoS One. 2007 Jun 20;2(6):e536. Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't

アルツハイマー病の治療標的としてのSOD-2活性

Reduction in mitochondrial superoxide dismutase modulates Alzheimer's disease-like pathology and accelerates the onset of behavioral changes in hum... - PubMed - NCBI
J Neurosci. 2006 May 10;26(19):5167-79. Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't

パーキンソン病、レビー小体型認知症患者での高いMn-SOD発現

Human brain cortex: mitochondrial oxidative damage and adaptive response in Parkinson disease and in dementia with Lewy bodies. - PubMed - NCBI
Free Radic Biol Med. 2009 Jun 15;46(12):1574-80. doi: 10.1016/j.freeradbiomed.2009.03.007. Epub 2009 Mar 17. Research Support, Non-U.S. Gov't

MnSODの神経保護効果

Manganese superoxide dismutase protects nNOS neurons from NMDA and nitric oxide-mediated neurotoxicity. - PubMed - NCBI
J Neurosci. 1998 Mar 15;18(6):2040-55. Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.; Review

 

SOD-2活性経路

PGC-1α

PPARγ

Sirt3

Activation of SIRT3 attenuates triptolide-induced toxicity through closing mitochondrial permeability transition pore in cardiomyocytes. - PubMed - NCBI
Toxicol In Vitro. 2016 Aug;34:128-137. doi: 10.1016/j.tiv.2016.03.020. Epub 2016 Apr 8.

Sirt1

N-acetyl-l-cysteine ameliorates the PM2.5-induced oxidative stress by regulating SIRT-1 in rats. - PubMed - NCBI
Environ Toxicol Pharmacol. 2018 Jan;57:70-75. doi: 10.1016/j.etap.2017.11.011. Epub 2017 Nov 20.

BDNF

Brain-derived neurotrophic factor increases expression of MnSOD in human circulating angiogenic cells. - PubMed - NCBI
Microvasc Res. 2012 May;83(3):366-71. doi: 10.1016/j.mvr.2012.01.001. Epub 2012 Jan 9. Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't

Nrf2(熱ショック)

The antioxidant transcription factor Nrf2 contributes to the protective effect of mild thermotolerance (40°C) against heat shock-induced apoptosis. - PubMed - NCBI
Free Radic Biol Med. 2016 Oct;99:485-497. doi: 10.1016/j.freeradbiomed.2016.08.032. Epub 2016 Aug 31.
SOD-2関連遺伝子SNPs

RS4880 G/G

SOD-2(MnSOD)活性剤

レスベラトロール

The stilbenes resveratrol, pterostilbene and piceid affect growth and stress resistance in mammalian cells via a mechanism requiring estrogen recep... - PubMed - NCBI
Phytochemistry. 2014 Feb;98:164-73. doi: 10.1016/j.phytochem.2013.11.019. Epub 2013 Dec 19. Research Support, Non-U.S. Gov't

プテロスチルベン

ERK5/HDAC5-mediated, resveratrol-, and pterostilbene-induced expression of MnSOD in human endothelial cells. - PubMed - NCBI
Mol Nutr Food Res. 2016 Feb;60(2):266-77. doi: 10.1002/mnfr.201500466. Epub 2015 Oct 23. Research Support, Non-U.S. Gov't

カテキン MnSOD

Time-dependent beneficial effect of chronic polyphenol treatment with catechin on endothelial dysfunction in aging mice. - PubMed - NCBI
Dose Response. 2012;10(1):108-19. doi: 10.2203/dose-response.11-014.Thorin. Epub 2011 Oct 14.

豆、穀物 MnSOD

Grain and bean lysates improve function of endothelial progenitor cells from human peripheral blood: involvement of the endogenous antioxidant defe... - PubMed - NCBI
PLoS One. 2014 Oct 17;9(10):e109298. doi: 10.1371/journal.pone.0109298. eCollection 2014. Research Support, Non-U.S. Gov't
Barley beta-glucan promotes MnSOD expression and enhances angiogenesis under oxidative microenvironment. - PubMed - NCBI
J Cell Mol Med. 2015 Jan;19(1):227-38. doi: 10.1111/jcmm.12442. Epub 2014 Nov 11. Research Support, Non-U.S. Gov't

カスチンViticis Fructus MnSOD

Casticin prevents DSS induced ulcerative colitis in mice through inhibitions of NF-κB pathway and ROS signaling. - PubMed - NCBI
Phytother Res. 2018 Sep;32(9):1770-1783. doi: 10.1002/ptr.6108. Epub 2018 Jun 7.

ルテイン SOD-2

Lutein extends the lifespan of Drosophila melanogaster. - PubMed - NCBI
Arch Gerontol Geriatr. 2014 Jan-Feb;58(1):153-9. doi: 10.1016/j.archger.2013.07.007. Epub 2013 Aug 8. Research Support, Non-U.S. Gov't

クルクミン SOD-2

Curcumin Ameliorates Arterial Dysfunction and Oxidative Stress with Aging
We tested the hypothesis that curcumin supplementation would reverse arterial dysfunction and vascular oxidative stress with aging. Young (Y, 4–6 mo) and old (O...
Curcumin-supplemented diets increase superoxide dismutase activity and mean lifespan in Drosophila. - PubMed - NCBI
Age (Dordr). 2013 Aug;35(4):1133-42. doi: 10.1007/s11357-012-9438-2. Epub 2012 Jun 1. Comparative Study

はちみつ SOD

The effects of honey supplementation on seminal plasma cytokines, oxidative stress biomarkers, and antioxidants during 8 weeks of intensive cycling... - PubMed - NCBI
J Androl. 2012 May-Jun;33(3):449-61. doi: 10.2164/jandrol.110.012815. Epub 2011 Jun 2. Randomized Controlled Trial

タンポポ(タラクサムオフィシナール) SOD

Taraxacum officinale protects against lipopolysaccharide-induced acute lung injury in mice. - PubMed - NCBI
J Ethnopharmacol. 2010 Jul 20;130(2):392-7. doi: 10.1016/j.jep.2010.05.029. Epub 2010 May 25. Research Support, Non-U.S. Gov't

エラグ酸 SOD

Antioxidant and apoptosis-inducing activities of ellagic acid. - PubMed - NCBI
Anticancer Res. 2006 Sep-Oct;26(5A):3601-6. Research Support, Non-U.S. Gov't

N-アセチル-システイン Sirt1経路

N-acetyl-l-cysteine ameliorates the PM2.5-induced oxidative stress by regulating SIRT-1 in rats. - PubMed - NCBI
Environ Toxicol Pharmacol. 2018 Jan;57:70-75. doi: 10.1016/j.etap.2017.11.011. Epub 2017 Nov 20.

SODの材料 銅、亜鉛、マンガン

ホルモン

エストロゲン

濃度、時間に依存して変動。

Molecular Vision: Mitochondrial superoxide dismutase activation with 17 β-estradiol-treated human lens epithelial cells

プロゲステロン

Estrogen plus progestin increase superoxide dismutase and total antioxidant capacity in postmenopausal women
(2015). Estrogen plus progestin increase superoxide dismutase and total antioxidant capacity in postmenopausal women. Climacteric: Vol. 18, No. 3, pp. 379-388.
筋力トレーニング

21週間の筋力トレーニングは健康な中年男性の抗酸化酵素を増加させたが、持久トレーニンググループでは有意な影響を与えなかった。

Effects of strength and endurance training on antioxidant enzyme gene expression and activity in middle-aged men. - PubMed - NCBI
Scand J Med Sci Sports. 2007 Oct;17(5):595-604. Epub 2007 Feb 19. Clinical Trial; Randomized Controlled Trial; Research Support, Non-U.S. Gov't
Exercise and hormesis: activation of cellular antioxidant signaling pathway. - PubMed - NCBI
Ann N Y Acad Sci. 2006 May;1067:425-35. Comparative Study; Review

SOD-2活性の低下

セレン

Selenium attenuates expression of MnSOD and uncoupling protein 2 in J774.2 macrophages: molecular mechanism for its cell-death and antiinflammatory... - PubMed - NCBI
Antioxid Redox Signal. 2005 Jan-Feb;7(1-2):276-86. Research Support, Non-U.S. Gov't
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