Glutathione： A Samsonian life-sustaining small molecule that protects against oxidative stress, ageing and damaging inflammation.; PY2022; USA (美國);_WJD_2023-0222_IR95_IR96_

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2023-02-22
Glutathione: A Samsonian life-sustaining small molecule that protects against oxidative stress, ageing and damaging inflammation
Source or References (資訊來源或是參考的資訊):
https://scientificresearchwj.blogspot.com/2023/02/glutathione-samsonian-life-sustaining.html
Info cited on 2023-02-22-WD3 (資訊引用於 中華民國112年西元2023年2月22日) by 湯偉晉 (WeiJin Tang)
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Source or References (資訊來源或是參考的資訊):
https://pubmed.ncbi.nlm.nih.gov/36386929/
Info cited on 2023-02-22-WD3 (資訊引用於 中華民國112年西元2023年2月22日) by 湯偉晉 (WeiJin Tang)
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Front Nutr
. 2022 Nov 1;9:1007816. doi: 10.3389/fnut.2022.1007816. eCollection 2022.
Glutathione: A Samsonian life-sustaining small molecule that protects against oxidative stress, ageing and damaging inflammation

Glutathione: A Samsonian life-sustaining small molecule that protects against oxidative stress, ageing and damaging inflammation

Glutathione: A Samsonian life-sustaining small molecule that protects against oxidative stress, ageing and damaging inflammation
Carlos A Labarrere 1, Ghassan S Kassab 1
Affiliations collapse
Affiliation
1 California Medical Innovations Institute, San Diego, CA, United States.
PMID: 36386929 PMCID: PMC9664149 DOI: 10.3389/fnut.2022.1007816
Free PMC article
Abstract
Many local and systemic diseases especially diseases that are leading causes of death globally like chronic obstructive pulmonary disease, atherosclerosis with ischemic heart disease and stroke, cancer and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causing coronavirus disease 19 (COVID-19), involve both, (1) oxidative stress with excessive production of reactive oxygen species (ROS) that lower glutathione (GSH) levels, and (2) inflammation. The GSH tripeptide (γ- L-glutamyl-L-cysteinyl-glycine), the most abundant water-soluble non-protein thiol in the cell (1-10 mM) is fundamental for life by (a) sustaining the adequate redox cell signaling needed to maintain physiologic levels of oxidative stress fundamental to control life processes, and (b) limiting excessive oxidative stress that causes cell and tissue damage. GSH activity is facilitated by activation of the Kelch-like ECH-associated protein 1 (Keap1)-Nuclear factor erythroid 2-related factor 2 (Nrf2)-antioxidant response element (ARE) redox regulator pathway, releasing Nrf2 that regulates expression of genes controlling antioxidant, inflammatory and immune system responses. GSH exists in the thiol-reduced (>98% of total GSH) and disulfide-oxidized (GSSG) forms, and the concentrations of GSH and GSSG and their molar ratio are indicators of the functionality of the cell. GSH depletion may play a central role in inflammatory diseases and COVID-19 pathophysiology, host immune response and disease severity and mortality. Therapies enhancing GSH could become a cornerstone to reduce severity and fatal outcomes of inflammatory diseases and COVID-19 and increasing GSH levels may prevent and subdue these diseases. The life value of GSH makes for a paramount research field in biology and medicine and may be key against systemic inflammation and SARS-CoV-2 infection and COVID-19 disease. In this review, we emphasize on (1) GSH depletion as a fundamental risk factor for diseases like chronic obstructive pulmonary disease and atherosclerosis (ischemic heart disease and stroke), (2) importance of oxidative stress and antioxidants in SARS-CoV-2 infection and COVID-19 disease, (3) significance of GSH to counteract persistent damaging inflammation, inflammaging and early (premature) inflammaging associated with cell and tissue damage caused by excessive oxidative stress and lack of adequate antioxidant defenses in younger individuals, and (4) new therapies that include antioxidant defenses restoration.

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許多局部和全身性疾病，尤其是導致全球死亡的主要原因的疾病，如慢性阻塞性肺病、動脈粥樣硬化伴缺血性心髒病和中風、癌症和嚴重急性呼吸系統綜合症冠狀病毒 2 (SARS-CoV-2) 引起的冠狀病毒病 19 (COVID- 19)，涉及兩者，(1) 氧化應激與活性氧 (ROS) 的過度產生降低穀胱甘肽 (GSH) 水平，和 (2) 炎症。 GSH 三肽（γ-L-谷氨酰-L-半胱氨酰-甘氨酸）是細胞中最豐富的水溶性非蛋白質硫醇 (1-10 mM)，通過 (a) 維持足夠的氧化還原細胞信號傳導是生命的基礎 需要維持氧化應激的生理水平，這是控制生命過程的基礎，以及 (b) 限制導致細胞和組織損傷的過度氧化應激。 GSH 活性通過激活 Kelch 樣 ECH 相關蛋白 1 (Keap1)-核因子紅細胞 2 相關因子 2 (Nrf2)-抗氧化反應元件 (ARE) 氧化還原調節通路，釋放調節基因表達的 Nrf2 來促進 抗氧化、炎症和免疫系統反應。 GSH 以硫醇還原（>98% 的總 GSH）和二硫化物氧化 (GSSG) 形式存在，GSH 和 GSSG 的濃度及其摩爾比是細胞功能的指標。 GSH 耗竭可能在炎症性疾病和 COVID-19 病理生理學、宿主免疫反應以及疾病嚴重程度和死亡率中發揮核心作用。 增強 GSH 的療法可能成為降低炎症性疾病和 COVID-19 嚴重程度和致命後果的基石，而提高 GSH 水平可能會預防和抑制這些疾病。 GSH 的生命價值使其成為生物學和醫學中最重要的研究領域，可能是對抗全身炎症和 SARS-CoV-2 感染和 COVID-19 疾病的關鍵。 在這篇綜述中，我們強調 (1) GSH 耗竭是慢性阻塞性肺病和動脈粥樣硬化（缺血性心髒病和中風）等疾病的基本危險因素，(2) 氧化應激和抗氧化劑在 SARS-CoV-2 感染中的重要性 和 COVID-19 疾病，(3) GSH 對抗持續性破壞性炎症、炎症和早期（過早）炎症的重要性，這些炎症與過度氧化應激和年輕個體缺乏足夠的抗氧化防禦引起的細胞和組織損傷相關，以及 (4) 包括抗氧化防禦恢復在內的新療法。
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Keywords: COVID-19; atherosclerosis; chronic obstructive pulmonary disease; glutathione; inflammaging; nuclear factor erythroid 2-related factor 2; oxidative stress; reactive oxygen species.

Copyright © 2022 Labarrere and Kassab.

Conflict of interest statement
The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures
FIGURE 1
FIGURE 1 Glutathione (GSH) synthesis, chemical structure…

FIGURE 2
FIGURE 2 Glutathione distribution in subcellular compartments.…

FIGURE 3
FIGURE 3 Glutathione synthesis: A two-step pathway.…

FIGURE 4
FIGURE 4 The “Glutathione Pathway.” Glutathione synthesis…

FIGURE 5
FIGURE 5 Cellular glutathione synthesis and recycling:…

FIGURE 6
FIGURE 6 Oxidative stress, reduced glutathione (GSH)…
All figures (9)
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L-cysteine efflux in erythrocytes as a function of human age: correlation with reduced glutathione and total anti-oxidant potential; PY2013; India (印度);_WJD_2023-0213_IR95_

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L-cysteine efflux in erythrocytes as a function of human age： correlation with reduced glutathione and total anti-oxidant potential; PY2013; India (印度);_WJD_2023-0213_IR95_.docx
L-cysteine efflux in erythrocytes as a function of human age: correlation with reduced glutathione and total anti-oxidant potential; PY2013; India (印度);_WJD_2023-0213_IR95_

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2023-02-13
L-cysteine efflux in erythrocytes as a function of human age: correlation with reduced glutathione and total anti-oxidant potential; PY2013; India (印度);_WJD_2023-0213_IR95_
Source or References (資訊來源或是參考的資訊):
https://pubmed.ncbi.nlm.nih.gov/23442131/
Info cited on 2023-02-13-WD1 (資訊引用於 中華民國112年西元2023年2月13日) by 湯偉晉 (WeiJin Tang)
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Rejuvenation Res
. 2013 Jun;16(3):179-84. doi: 10.1089/rej.2012.1394.
L-cysteine efflux in erythrocytes as a function of human age: correlation with reduced glutathione and total anti-oxidant potential

L-cysteine efflux in erythrocytes as a function of human age: correlation with reduced glutathione and total anti-oxidant potential

L-cysteine efflux in erythrocytes as a function of human age: correlation with reduced glutathione and total anti-oxidant potential
Prabhanshu Kumar 1, Pawan Kumar Maurya
Affiliations collapse
Affiliation
1Amity Institute of Biotechnology, Amity University Uttar Pradesh, Noida, India.
PMID: 23442131 DOI: 10.1089/rej.2012.1394
Abstract
Thiol compounds such as cysteine (Cys) and reduced glutathione (GSH) play an important role in human aging and age-related diseases. In erythrocytes, GSH is synthesized by glutamic acid, cysteine, and glycine, but the rate of GSH synthesis is determined only by the availability of L-cysteine. Cysteine supplementation has been shown to ameliorate (改善，使變好) several parameters that are known to degenerate during human aging. We have studied L-cysteine efflux in vitro in human erythrocytes as a function of age by suspending cells in solution containing 10 mM L-cysteine for uptake; later cells were re-suspended in phosphate-buffered saline (PBS)-glucose to allow efflux. Change in the free sulfhydryl (-SH) concentration was then measured to calculate the rate of efflux. The GSH/oxidized glutathione (GSSG) ratio was taken as a control to study the oxidation/reduction state of the erythrocyte. The total anti-oxidant potential of plasma was measured in terms of ferric reducing ability of plasma (FRAP) values. We have shown a significant (p<0.0001) decline in the efflux of L-cysteine in erythrocytes during human aging, and the GSH/GSSG ratio decreases as a function of human age. The decline in L-cysteine efflux during aging correlates with the decrease in GSH and the FRAP value. This finding may help to explain the shift in the redox status and low GSH concentration that might determine the rate of L-cysteine efflux observed in erythrocytes and an important factor in the development of oxidative stress in erythrocytes during aging.

 

 

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(請注意：電腦自動翻譯的內容，可能會夾雜一些錯誤！)
半胱胺酸 (Cys) 和還原型穀胱甘肽 (GSH) 等硫醇化合物在人類衰老和與年齡相關的疾病中起著重要作用。在紅血球中，GSH 由谷胺酸、半胱胺酸和甘胺酸合成，但 GSH 合成速率僅由 L-半胱胺酸的可用性決定。已證明補充半胱胺酸可以改善已知在人類衰老過程中退化的幾個參數。我們通過將細胞懸浮在含有 10 mM L-半胱胺酸的溶液中進行吸收，研究了人紅血球體外 L-半胱胺酸流出與年齡的關係； 後來的細胞被重新懸浮在磷酸鹽緩衝鹽水（PBS）-葡萄糖中以允許流出。然後測量游離巰基 (-SH) 濃度的變化以計算流出率。GSH/氧化型穀胱甘肽 (GSSG) 比率作為對照來研究紅血球的氧化/還原狀態。根據血漿鐵還原能力 (FRAP) 值測量血漿的總抗氧化潛力。我們已經表明，在人類衰老過程中，紅血球中 L-半胱胺酸的流出顯著 (p<0.0001) 下降，並且 GSH/GSSG 比率隨著人類年齡的增長而下降。衰老過程中 L-半胱胺酸外流的下降與 GSH 和 FRAP 值的下降相關。這一發現可能有助於解釋氧化還原狀態的變化和低穀胱甘肽濃度，這可能決定了在紅血球中觀察到的 L-半胱胺酸流出率，並且是紅血球在衰老過程中氧化壓力發展的重要因素。
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