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Shigella: Insights into the Clinical Features, Pathogenesis, Diagnosis, and Treatment Strategies
Published in Dongyou Liu, Handbook of Foodborne Diseases, 2018
Periyanaina Kesika, Bhagavathi Sundaram Sivamaruthi, Krishnaswamy Balamurugan
Shigella move rapidly in the epithelial cytosol by means of actin-based motility, which is mediated by the outer membrane protein IcsA.48 SopA is a protease that is required for the secretion and localization of IcsA at one pole of Shigella.49 The actin-based motility and interaction of cadherin with the actin tail provide a driving force for the formation of a rigid protrusion structure at the intermediate junction of epithelial cells.50 After the protrusion entered the neighboring epithelial cell, Shigella rapidly destroy the double membrane–bounded compartment (protrusion) using a similar mechanism involved for the disruption of a single-membrane vacuole in an epithelial cell. Also, the bacterial periplasmic protein disulfide bond catalyst DsbA is required for the oxidative folding of Spa32, which is a component of the T3S system. The thiol sulfide oxidoreductase, DsbA-mediated Spa32 folding is essential for Shigella, which aids in the secretion of Ipa effector proteins and lysis of interepithelial protrusions formed during cell-to-cell spread.51–53 Along with the effectors IpaB and IpaC, cytosolic chaperone, IpgC (invasion plasmid gene) are involved in the lysis of double-membrane vacuole (protrusion membranes).54,55
Untargeted proteomics reveals upregulation of stress response pathways during CHO-based monoclonal antibody manufacturing process leading to disulfide bond reduction
Published in mAbs, 2021
Seo-Young Park, Susan Egan, Anthony J. Cura, Kathryn L. Aron, Xuankuo Xu, Mengyuan Zheng, Michael Borys, Sanchayita Ghose, Zhengjian Li, Kyongbum Lee
Protein folding activity in the ER can itself be a source of ROS generation. Folding and re-folding of unfolded or misfolded proteins within the ER is facilitated by protein disulfide isomerase (PDI), which catalyzes disulfide bond formation and isomerization.55 Oxidative folding by PDI results in the reduction of the isomerase, which needs to be regenerated to its oxidized form by oxidizing enzymes such as ERO1. This, in turn, generates H2O2 as a byproduct (Figure 5, #4). We also found increased abundance of several antioxidant enzymes in the rolled condition, including TRXR1, GSR, and glutathione-S-transferase (Figure 1e, f). In concert with the glutathione (GSH) reductase system, the TRXR system protects against oxidative damage to macromolecules56 by reducing oxidized cysteine and methionine residues (Figure 5, #5).
Rutin hydrate inhibits apoptosis in the brains of cadmium chloride-treated rats via preserving the mitochondrial integrity and inhibiting endoplasmic reticulum stress
Published in Neurological Research, 2019
Dalia G. Mostafa, Eman F. Khaleel, Rehab M. Badi, Ghada A. Abdel-Aleem, Hanaa M. Abdeen
For example, Geldanamycin, an anticancer agent, caused expression of GRP78 and activated UPR via a ROS_dependent mechanism in tumor cells of rat’s brain [48]. Similarly, peroxynitrite (ONOO_), a potent oxidant, caused a modest increase in GRP78 and GRP94 proteins in cultured human vascular endothelial cells through the depletion of ER Ca2+ and through direct interaction with the ER [48]. Yokouchi et al. [24], not only have shown that UPR occurs downstream to Cd_induced oxidative stress in the porcine renal proximal tubular cell line (LLC_PK1) exposed to Cd ions, but they also showed selective pathway activation by ROS. On the contrary, Haynes et al. [49], showed that during UPR in yeast cells, reactive oxygen species were produced from two sources; the oxidative folding machinery in the ER and the mitochondria. In their study, scavenging ROS by over_expressing GSH prevented the induced apoptosis but did not inhibit the UPR in these cells.
Advances in venom peptide drug discovery: where are we at and where are we heading?
Published in Expert Opinion on Drug Discovery, 2021
Taylor B. Smallwood, Richard J. Clark
The chemical synthesis of venom-derived peptides can be challenging, as most are around 30–40 amino acids long and many contain several disulfide bonds. Improvement in synthetic methodology such as native chemical ligation and automated solid phase peptide synthesis, as well as recombinant expression allow for the ability to produce structurally complex peptides. The formation of the correct disulfide isomer within a peptide is crucial for peptide activity. The linkage of a disulfide bond is a oxidation reaction involving the thiol groups of two cysteine residues. A peptide that has multiple cysteine residues within its sequence has the possibility to create multiple disulfide bond isomers. For example, a peptide with four, six, or eight cysteines can potentially form 3, 15, or 105 different disulfide isomers respectively. Incorrect pairing of disulfide bonds can lead to a non-native fold of the peptide and therefore loss of bioactivity. The chemical method for disulfide bond formation in cysteine-rich peptides is typically subjecting the reduced peptide to a freely oxidative folding reaction. This process generally provides the native disulfide bond pairing; however, this needs to be verified as some isomers can still occur. In order to overcome incorrect disulfide bond pairing, an alternative option is available known as a regioselective strategy. This method involves the stepwise formation of disulfide bonds, accomplished using various orthogonally protected cysteine residues [95–97]. The advancement of these methods should allow for the accelerated synthesis of venom-derived peptides in the peptide drug development pipeline.