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Role of Ascorbate and Dehydroascorbic Acid in Metabolic Integration of the Cell
Published in Qi Chen, Margreet C.M. Vissers, Vitamin C, 2020
Gábor Bánhegyi, András Szarka, József Mandl
In summary, there are several characteristics of vitamin C that make it appropriate to play a special role in the integration of intermediary metabolism in the cells at the organelle level. The unique redox moieties (e.g., pro- and antioxidant) of ascorbate/dehydroascorbate redox couple among the various redox active compounds.The coenzyme role of ascorbate in various enzyme complexes, which have either essential regulatory (e.g., HIF) or also structural (e.g., collagen) functions.The different regulations of concentrations of the reduced and oxidized form of the redox pair, ascorbate versus dehydroascorbate. It is noted that the latter is kept low, compared to ascorbate, which might suggest a possible regulatory role of dehydroascorbate. Recent data on their indirect impact on gene expression confirm these speculations.The multiorganelle aspects of processes, where ascorbate is involved (e.g., protein folding).The characteristic role of ascorbate in various organelle functions, and the functions of ascorbate transporters in them.
Biochemical Aspects of Nickel Hypersensitivity: Factors Determining Allergenic Action
Published in Jurij J. Hostýnek, Howard I. Maibach, Nickel and the Skin, 2019
Baldassarré Santucci, Emanuela Camera, Mauro Picardo
The Ni(II)/Ni(III) redox couple is active in biological systems because in aqueous solutions electrochemical oxidation of Ni(II) complexes can produce Ni(III) species (Cross et al., 1985). The likelihood that nickel can undergo redox cycling between Ni(II) and Ni(III) implies a geometrical reorganization and may play a role in its toxicity (Cross et al., 1985; Nieboer et al., 1984).
Cardiovascular Disease and Oxidative Stress
Published in Peter Grunwald, Pharmaceutical Biocatalysis, 2019
Marco Fernandes, Alisha Patel, Holger Husi
Redox homeostasis is the essential balance of a cell’s oxidation and reduction systems. Within a cellular response (i.e. signaling, apoptosis, detoxification, repair, and cell cycle arrest), maintaining redox homeostasis is dependent (Ursini et al., 2016). Redox homeostasis is responsible for kick-starting oxidant production and bypassing antioxidant mechanisms. When there is an imbalance of redox homeostasis, ROS levels increase and causes problems for cellular processes (i.e. signaling, adaption, cell cycle arrest, apoptosis, and detoxification repair/cell defense) (Ayer et al., 2014). Maintaining redox homeostasis is essential for cellular processes. In order for redox homeostasis to be effective the redox couple (i.e. NAD+/NADH and NADP+/NADPH) has to have high concentration levels and reducing at a high capacity (Valko et al., 2007).
High-throughput screening in multicellular spheroids for target discovery in the tumor microenvironment
Published in Expert Opinion on Drug Discovery, 2020
Blaise Calpe, Werner J. Kovacs
Genetically encoded fluorescent redox sensors have been developed for H2O2 and to monitor the redox state of GSSG/2GSH, NADH/NAD+, NADPH/NADP+, and TRXSS/TRXSH2 [84–86]. These redox indicators include redox-sensing fluorescent proteins such as Redoxfluor, Hyper, Peredox, and redox-sensitive yellow fluorescent protein (rxYFP) and green fluorescent proteins (roGFPs) [87]. RoGFP is more commonly used than rxYFP for two reasons: 1) unlike rxYFP, roGFP is ratiometric and thus provides a more quantitative measurement; 2) roGFP variants are pH resistant, whereas rxYFP is pH sensitive in the physiological pH range. Importantly, redox potentials differ in subcellular compartments and these reporters can be genetically targeted to specific subcellular compartments. RoGFPs are not directly oxidized by ROS, but equilibrate with the glutathione redox couple (GSH/GSSG) through the action of endogenous glutaredoxins (GRXs) [88]. For example, the redox sensor Grx1-roGFP, a fusion protein consisting of roGFP and human glutaredoxin 1, allows for ratiometric measurements and qualifies it as reporter for imaging of compound-mediated effects in real-time [89]. Importantly, this sensor was used in MTS, providing a proof of concept for redox-based imaging in 3D culture [90].
Stimuli-responsive drug delivery systems for head and neck cancer therapy
Published in Drug Delivery, 2021
Jingou Liang, Bina Yang, Xuedong Zhou, Qi Han, Jing Zou, Lei Cheng
As mentioned above, the increased generation of ROS induced high levels of oxidative stress in cancer cells, which also results in the compensatory upregulation of antioxidant. The reducing environment of tumors has been considered as an important target and biomarker of cancer, including HNC. The glutathione (GSH)/glutathione disulfide (GSSG) couple has been reported the most abundant redox couple in cancer cells. The concentration of GSH in tumor tissues has been found much higher than that in normal tissue (Bansal & Simon, 2018; Guo et al., 2018). The research on redox-responsive DDSs showed another novel strategy for the treatment of HNC. The redox-responsive linkers are incorporated in the carriers such as disulfide bonds and diselenide bonds, which could be cleavage by GSH, leading to controlled drug release (Huo et al., 2014) (Figure 1(D)). Sun et al. (2018) designed redox-responsive nanoscale micelles carrying doxorubicin for the treatment of laryngopharyngeal carcinoma. The micelles based on the heparosan (HEP) and deoxycholic acid conjugates (HSDs) could be internalized by human pharynx squamous carcinoma cell lines (FaDu cell) through clathrin-mediated endocytosis. With the link of disulfide bonds, the DDS demonstrated GSH-triggered drug release and significantly inhibited tumor cell growth. Fan, Wang, et al. (2020) reported a GSH-sensitive conjugated with disulfide bonds as well. The folate-targeted nanoparticles loaded with paclitaxel for the OSCC showed enhanced antitumor effect in vitro and in vivo. The research on redox-responsive DDSs is still limited right now. More research on multifunctional redox-responsive DDSs could be further conducted in the future.
Hepatoprotective effects of vitamin E against hexachlorobenzene-induced hepatotoxicity and oxidative stress in rats: histological, biochimical and antioxidant status changes
Published in Toxicology Mechanisms and Methods, 2019
Hela Chalouati, Mohamed Moncef Ben Sâad, Laurence Payrastre
GSH displayed a remarkable metabolic and a regulatory versatility. GSH/GSSG is the most important redox couple and plays a crucial role in antioxidant defense system. Results of our work showed that GSH content in the liver of HCB treated rats were significantly increased (p < 0.001) as compared to control group. The GSH levels increased by 38% and 37% in the HCB treated group with 4 mg and 16 mg/kg b.w. respectively. However, the GSH content was found to be significantly decreased in rats treated with HCB along with vitamin E as compared to HCB treated groups.