Glutathione and glutathione-dependent enzymes: From biochemistry to gerontology and successful aging

Lapenna, Domenico

doi:10.1016/j.arr.2023.102066

Cited by 32 publications

(6 citation statements)

References 259 publications

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“…The sulfhydryl group (SH) of GSH is readily polarizable and facilitates the removal of free radicals and their derivatives ( Gomes et al ., 2023 ). Further, tripeptide GSH acts as the cofactor for glutathione peroxidation and is, therefore, involved in the detoxification of electrophilic compounds ( Lapenna, 2023 ). As suppressed GSH levels disturb the cellular antioxidant capacity, the RA-induced increase in GSH content largely enhances the antioxidant status of the skin, thereby protecting against UVB-induced oxidative damage.…”

Section: Discussionmentioning

confidence: 99%

Rosmarinic Acid Inhibits Ultraviolet B-Mediated Oxidative Damage via the AKT/ERK-NRF2-GSH Pathway In Vitro and In Vivo

Piao,

Fernando,

Kang

et al. 2024

Biomol Ther (Seoul)

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Rosmarinic acid (RA) is a phenolic ester that protects human keratinocytes against oxidative damage induced by ultraviolet B (UVB) exposure, however, the mechanisms underlying its effects remain unclear. This study aimed to elucidate the cell signaling mechanisms that regulate the antioxidant activity of RA and confirm its cyto-protective role. To explore the signaling mechanisms, we used the human keratinocyte cell line HaCaT and SKH1 hairless mouse skin. RA enhanced glutamate-cysteine ligase catalytic subunit (GCLC) and glutathione synthetase (GSS) expression in HaCaT cells in a dose- and time-dependent manner. Moreover, RA induced nuclear factor erythroid-2-related factor 2 (NRF2) nuclear translocation and activated the signaling kinases protein kinase B (AKT) and extracellular signal-regulated kinase (ERK). Treatment with the phosphatidylinositol 3-kinase (PI3K) inhibitor LY294002, the ERK inhibitor U0126, and small interfering RNA (siRNA) gene silencing suppressed RA-enhanced GCLC, GSS, and NRF2 expression, respectively. Cell viability tests showed that RA significantly prevented UVB-induced cell viability decrease, whereas the glutathione (GSH) inhibitors buthionine sulfoximine, LY294002, and U0126 significantly reduced this effect. Moreover, RA protected against DNA damage and protein carbonylation, lipid peroxidation, and apoptosis caused by UVB-induced oxidative stress in a concentration-dependent manner in SKH1 hairless mouse skin tissues. These results suggest that RA protects against UVB-induced oxidative damage by activating AKT and ERK signaling to regulate NRF2 signaling and enhance GSH biosynthesis. Thus, RA treatment may be a promising approach to protect the skin from UVB-induced oxidative damage.

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Section: Discussionmentioning

confidence: 99%

Rosmarinic Acid Inhibits Ultraviolet B-Mediated Oxidative Damage via the AKT/ERK-NRF2-GSH Pathway In Vitro and In Vivo

Piao,

Fernando,

Kang

et al. 2024

Biomol Ther (Seoul)

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“…GSH is a biologically active polypeptide composed of glutamic acid, cysteine, and glycine, containing a γ -amide bond and sulfhydryl groups ( 53 ). GSH is widely distributed in animals and plants and plays a crucial role in various biological processes, including DeoxyriboNucleic Acid (DNA) and protein synthesis, amino acid transport, gene expression, and cell proliferation and apoptosis ( 54 , 55 ). In the context of CVDs, GSH serves as a marker for prophylactic antioxidant therapy and the risk of adverse cardiovascular events ( 56 ).…”

Section: Discussionmentioning

confidence: 99%

Causal associations between chronic heart failure and the cerebral cortex: results from Mendelian randomization study and integrated bioinformatics analysis

Peng,

Cai,

Tang

et al. 2024

Front. Cardiovasc. Med.

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BackgroundChronic heart failure (CHF) patients exhibit alterations in cerebral cortical structure and cognitive function. However, the mechanisms by which CHF affects cortical structure and functional regions remain unknown. This study aims to investigate potential causal relationship between CHF and cerebral cortical structure through Mendelian randomization (MR).MethodsThe research utilized genome-wide association studies (GWAS) to explore the causal association between CHF and cerebral cortical structure. The results were primarily analyzed using the inverse-variance weighted (IVW). The reliability of the data was verified through horizontal pleiotropy and heterogeneity analysis by MR-Egger intercept test and Cochran's Q-test, respectively. Replication analysis was conducted in the Integrative Epidemiology Unit (IEU) OpenGWAS project for further validation. In addition, we collected mediator genes that mediate causality to reveal potential mechanisms. Integrated bioinformatics analysis was conducted using the Open Target Genetics platform, the STRING database, and Cytoscape software.ResultsThe IVW results did not reveal any significant causal association between genetically predicted CHF and the overall structure of the cerebral cortex or the surface area (SA) of the 34 functional regions of the cerebral cortex (P > 0.05). However, the results revealed that CHF increased the thickness (TH) of pars opercularis (IVW: β = 0.015, 95% CI: 0.005–0.025, P = 3.16E-03). Replication analysis supported the causal association between CHF and pars opercularis TH (IVW: β = 0.02, 95% CI: 0.010–0.033, P = 1.84E-04). We examined the degree centrality values of the top 10 mediator genes, namely CDKN1A, CELSR2, NME5, SURF4, PSMA5, TSC1, RPL7A, SURF6, PRDX3, and FTO.ConclusionGenetic evidence indicates a positive correlation between CHF and pars opercularis TH.

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“…The mutation of cysteine to serine (C47S) in Prdx6 can eliminate its ability to reduce hydroperoxides [18,19]. Prdx6, as a peroxidase, has substrate specificity, and its substrates include H 2 O 2 , short-chain hydroperoxides, and phospholipid hydroperoxides [20,21]. Prdx6 binds to oxidized lipid substrates (oxidized membrane phospholipids) and reduces the generation of phospholipid hydroperoxides induced by oxidative stress [22,23].…”

Section: Enzyme Activities and Function Of Prdx6mentioning

confidence: 99%

Unveiling the Significance of Peroxiredoxin 6 in Central Nervous System Disorders

Xue,

Huang,

Zhu

et al. 2024

Antioxidants

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Peroxiredoxin 6 (Prdx6), a unique 1-Cys member of the peroxiredoxin family, exhibits peroxidase activity, phospholipase activity, and lysophosphatidylcholine acyltransferase (LPCAT) activity. Prdx6 has been known to be an important enzyme for the maintenance of lipid peroxidation repair, cellular metabolism, inflammatory signaling, and antioxidant damage. Growing research has demonstrated that the altered activity of this enzyme is linked with various pathological processes including central nervous system (CNS) disorders. This review discusses the distinctive structure, enzyme activity, and function of Prdx6 in different CNS disorders, as well as emphasizing the significance of Prdx6 in neurological disorders.

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Glutathione and glutathione-dependent enzymes: From biochemistry to gerontology and successful aging

Cited by 32 publications

References 259 publications

Rosmarinic Acid Inhibits Ultraviolet B-Mediated Oxidative Damage via the AKT/ERK-NRF2-GSH Pathway In Vitro and In Vivo

Rosmarinic Acid Inhibits Ultraviolet B-Mediated Oxidative Damage via the AKT/ERK-NRF2-GSH Pathway In Vitro and In Vivo

Causal associations between chronic heart failure and the cerebral cortex: results from Mendelian randomization study and integrated bioinformatics analysis

Unveiling the Significance of Peroxiredoxin 6 in Central Nervous System Disorders

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