Glutathione- and non-glutathione-based oxidant control in the endoplasmic reticulum

Appenzeller-Herzog, Christian

doi:10.1242/jcs.080895

Cited by 139 publications

(116 citation statements)

References 86 publications

(128 reference statements)

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“…Another important maturation step in the ER is the formation of disulfide bonds, which are crucial for protein function and stability (Appenzeller-Herzog 2011). The oxidative environment of the ER is suitable for the oxidation of free sulfhydryl (SH) groups on cysteines to form disulfide (S-S) bonds.…”

Section: Disulfide Bond Formationmentioning

confidence: 99%

Protein Folding and Quality Control in the ER

Araki

Nagata

2011

Cold Spring Harbor Perspectives in Biology

318

285

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The endoplasmic reticulum (ER) uses an elaborate surveillance system called the ER quality control (ERQC) system. The ERQC facilitates folding and modification of secretory and membrane proteins and eliminates terminally misfolded polypeptides through ER-associated degradation (ERAD) or autophagic degradation. This mechanism of ER protein surveillance is closely linked to redox and calcium homeostasis in the ER, whose balance is presumed to be regulated by a specific cellular compartment. The potential to modulate proteostasis and metabolism with chemical compounds or targeted siRNAs may offer an ideal option for the treatment of disease.

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Section: Disulfide Bond Formationmentioning

confidence: 99%

Protein Folding and Quality Control in the ER

Araki

Nagata

2011

Cold Spring Harbor Perspectives in Biology

318

285

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“…the reduction of protein disulfide bonds, in the same compartment and suggests that the redox state of PDI is tightly regulated to facilitate both the formation (oxidation) and reduction of disulfides. Importantly, an enzyme reducing the oxidized PDI is not known, but the process is either directly or indirectly dependent on GSH (Appenzeller-Herzog, 2011). Another folding process that occurs in the ER (not shown in Fig.…”

Section: Oxidative Stress In the Ermentioning

confidence: 99%

Proteomic responses to environmentally induced oxidative stress

Tomanek

2015

Journal of Experimental Biology

137

132

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Environmental (acute and chronic temperature, osmotic, hypoxic and pH) stress challenges the cellular redox balance and can lead to the increased production of reactive oxygen species (ROS). This review provides an overview of the reactions producing and scavenging ROS in the mitochondria, endoplasmic reticulum (ER) and peroxisome. It then compares these reactions with the findings of a number of studies investigating the proteomic responses of marine organisms to environmentally induced oxidative stress. These responses indicate that the thioredoxin-peroxiredoxin system is possibly more frequently recruited to scavenge H 2 O 2 than the glutathione system. Isoforms of superoxide dismutase (SOD) are not ubiquitously induced in parallel, suggesting that SOD scavenging activity is sometimes sufficient. The glutathione system plays an important role in some organisms and probably also contributes to protecting protein thiols during environmental stress. Synthesis pathways of cysteine and selenocysteine, building blocks for glutathione and glutathione peroxidase, also play an important role in scavenging ROS during stress. The increased abundance of glutaredoxin and DyP-type peroxidase suggests a need for regulating the deglutathionylation of proteins and scavenging of peroxynitrite. Reducing equivalents for these scavenging reactions are generated by proteins of the pentose phosphate pathway and by NADP-dependent isocitrate dehydrogenase. Furthermore, proteins representing reactions of the tricarboxylic acid cycle and the electron transport system generating NADH and ROS, including those of complex I, II and III, are frequently reduced in abundance with stress. Protein maturation in the ER likely represents another source of ROS during environmental stress, as indicated by simultaneous changes in ER chaperones and antioxidant proteins. Although there are still too few proteomic analyses of non-model organisms exposed to environmental stress for a general pattern to emerge, hyposaline and low pH stress show different responses from temperature and hypoxic stress. Furthermore, comparisons of closely related congeners differing in stress tolerance start to provide insights into biochemical processes contributing to adaptive differences, but more of these comparisons are needed to draw general conclusions. To fully take advantage of a systems approach, studies with longer time courses, including several tissues and more species comparisons are needed.

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“…GSH is also involved in direct reactions with a variety of oxidants in a non-enzymatic manner that results in its conversion to its dimeric oxidized form (i.e. glutathione disulfide, GSSG) (Appenzeller-Herzog, 2011). By breaking the disulfide bonds with NaBH 4 , all of the available thiol (-SH) groups can be converted to their reduced form (Table 2), which provides an opportunity to link a large quantity of NO molecules (e.g.…”

Section: Synthesis Of Alginate-glutathione Conjugatesmentioning

confidence: 99%

Synthesis of S-nitrosoglutathione-alginate for prolonged delivery of nitric oxide in intestines

et al. 2015

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S-nitrosothiols are a class of NO-donors currently under investigation for the treatment of various diseases. In this study, we developed a novel NO-donor (S-nitrosoglutathione-alginate, SNA) by cross-linking alginate with S-nitrosothiols, which can deliver NO in a sustained manner. This compound can be further evaluated for oral delivery to treat Crohn's disease. This new compound was prepared using a two-step procedure involving (I) linkage of reduced glutathione to alginate and (II) post-nitrosation with sodium nitrite (NaNO 2 ). The amount of linked thiol moieties for the possible nitrosation was calculated using Ellman's method, and the amount of NO abducted on the polymer was calculated using the Griess-Saville method. An ex vivo model (i.e. Ussing chamber) was used to investigate the permeation of this new NO-donor across the rat intestinal barrier. We obtained polymers with different numbers of abducted NOs (174 ± 21 mmol/g for SNA F1 and 468 ± 23 mmol/g for SNA F2) depending on the procedure used for nitrosation. In the ex vivo studies in the Ussing chamber, SNA F2 exhibited a sustained release for at least 10 h. The effect of pH on the stability of the new compound was also investigated, and the new compound was more stable at a mildly basic pH of 8.4 where 73% remained after 1 week. However, only 50% remained after 1 week at an acidic pH of 1.2. In the cytotoxicity studies (Caco2), this compound was nontoxic at concentrations of less than 200 mM.

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Glutathione- and non-glutathione-based oxidant control in the endoplasmic reticulum

Cited by 139 publications

References 86 publications

Protein Folding and Quality Control in the ER

Protein Folding and Quality Control in the ER

Proteomic responses to environmentally induced oxidative stress

Synthesis of S-nitrosoglutathione-alginate for prolonged delivery of nitric oxide in intestines

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