Time to ‘Couple’ Redox Biology with Exercise Immunology
James N. Cobley, Gareth W. Davison in Oxidative Eustress in Exercise Physiology, 2022
The role of cysteine thiols in regulating immune responses to exercise is a recent area of investigation, with emerging data indicating that exercise might cause reductive stress in immune cells after exercise (Wadley et al., 2018a,b; Spanidis et al., 2018). A series of dietary intervention studies have indicated that supplementation with the thiol donor, N-acetylcysteine (NAC) can blunt immune cell mobilisation patterns in response to both muscle-damaging (Michailidis et al., 2013; Sakelliou et al., 2016) and exhaustive aerobic exercise (Petersen et al., 2012). Although the exact tissue uptake kinetics are unclear, this data suggests that alterations in the thiol redox state of immune cells or other tissues (i.e., increased reductive capacity) may regulate immunity after exercise. Spanidis et al. (2018) stratified participants into ‘oxidative’ and ‘reductive’ groups based on their individual changes from rest in erythrocyte reduced glutathione (GSH) concentration following a muscle-damaging protocol (i.e., increase in GSH was termed ‘reductive’) (Spanidis et al., 2018). PBMCs isolated at the same timepoints from the ‘oxidative’ participants were more sensitive to in vitro oxidation and had lower catalase activity compared to ‘reduced’ participants. This suggests that the reductive capacity of PBMCs could be important for governing their function, although the exact nature is unclear. Furthermore, both the above studies did not account for compositional shifts in immune cell populations after exercise.
Chimeric VLPs
Paul Pumpens in Single-Stranded RNA Phages, 2020
Three of the five, namely, G13, G14, and T15, were located in the AB-loop, a short β-turn that connected the A and B β-strands of coat protein. The other two, D114 and G115, resided in a loop connecting the two coat protein α-helices (for more structural detail, see Chapter 21). Each of these five amino acids was converted to cysteine by site-directed mutagenesis, and the mutant genes were cloned and expressed. In the four of the five mutant cases, namely, G13C, G14C, D114C, and G115C, no VLPs were detected and the coat proteins were found predominantly in the insoluble fraction of cell lysates. An attempt to suppress the effects of these mutations on the MS2 coat folding/stability by incorporating them into the single-chain MS2 coat dimers was unsuccessful. In contrast to the destabilizing substitutions, the T15C mutant produced significant quantities of soluble coat protein that assembled into particles with the same electrophoretic mobility as the wild-type virus. The accessibility of the new cysteine was further illustrated by its active reaction with thiol-specific chemical reagents (Peabody 2003). This study therefore generated for the first time the RNA phage scaffold, to which a variety of substances could be chemically attached in definite geometric patterns. Moreover, the reaction with fluorescein-5-maleimide imparted green fluorescence to the mutant particle.
Topical Products Applied to the Nail
Heather A.E. Benson, Michael S. Roberts, Vânia Rodrigues Leite-Silva, Kenneth A. Walters in Cosmetic Formulation, 2019
The nail plate chemically comprises of fibrous protein called keratin that provides the necessary mechanical strength to the epithelial cells. Keratins found in humans are either hair keratin or epithelial keratin. Nearly about 80–90% of the keratin present in the nail is the hair keratin, while the rest would be the epithelial keratin. Hair keratin is found to be concentrated in the intermediate layer of the nail plate, while the epithelial keratin is present in the dorsal and ventral layers. Keratin fibres in the nail plate are interconnected through cysteine-rich proteins which are linked via disulphide bridges. This sandwich orientation of keratin fibres imparts the necessary hardness and rigidity to the nail plate (Kobayashi et al., 1999).
Expression of urinary exosomal miRNA-615-3p and miRNA-3147 in diabetic kidney disease and their association with inflammation and fibrosis
Published in Renal Failure, 2023
Jiaxin Wang, Yiying Tao, Fan Zhao, Tong Liu, Xiahong Shen, Ling Zhou
As a traditional inflammatory indicator, Cystatin C not only reflects the degree of renal damage but is also one of the important indicators of the micro-inflammatory state in DKD patients [46]. Cystatin C is a low molecular weight protein (13KD) produced by all nucleated human cells and is primarily catabolized by proximal tubular cells [47]. As an endogenous inhibitor of cysteine protein, it is not affected by age, gender, muscle mass, or protein intake [48]. However, studies [46] have shown that serum Cystatin C is positively correlated with the micro-inflammatory state of DKD and related inflammatory factors. Cystatin C is not only correlated with eGFR and other indicators of renal function damage but also in evaluating the degree and progression of inflammatory response in the course of DKD. The present study provided evidence that the expression level of urinary exosomal miRNA-615-3p correlated with serum Cystatin C, so urinary exosomal miRNA-615-3p might be useful as a marker of the inflammatory response and the progression of kidney damage in DKD.
Increased plasma glutamate in non-smokers with vasospastic angina pectoris is associated with plasma cystine and antioxidant capacity
Published in Scandinavian Cardiovascular Journal, 2022
Minako Oda, Kousuke Fujibayashi, Minoru Wakasa, Shintaro Takano, Wataru Fujita, Michihiko Kitayama, Hiroaki Nakanishi, Kazuyuki Saito, Yasuyuki Kawai, Kouji Kajinami
In addition to oxidative stress, decreased antioxidant capacity may be responsible for endothelial dysfunction. Glutathione is an important antioxidant that attenuates coronary vasospasm in patients with vasospastic angina pectoris (VSAP) [11] and reverses endothelial dysfunction in patients with atherosclerosis [12]. The synthesis of glutathione depends on the availability of the amino acid precursors, glutamate, glycine and cysteine [13]. Cystine is an oxidative form comprising two cysteines that are taken up by a specific cystine/glutamate antiporter system (XC–) in association with glutamate export. Extracellular glutamate competitively inhibits cystine import into endothelial cells [14–16]. Therefore, extracellular glutamate and cystine concentrations are crucial for glutathione biosynthesis.
Regenerative responses of rabbit corneal endothelial cells to stimulation by fibroblast growth factor 1 (FGF1) derivatives, TTHX1001 and TTHX1114
Published in Growth Factors, 2021
Jessica Weant, David D. Eveleth, Amuthakannan Subramaniam, Jennifer Jenkins-Eveleth, Michael Blaber, Ling Li, David M. Ornitz, Asaf Alimardanov, Trevor Broadt, Hui Dong, Vinay Vyas, Xiaoyi Yang, Ralph A. Bradshaw
TTHX1001, containing K12V, C117V, and P134V substitutions was expressed as the N-Phe, 140 amino acid form of human FGF1 as described (Xia et al. 2012). Some preparations also had an N-terminal extension containing a His-tag sequence for purification purposes (Brych et al. 2001). TTHX1114, which is characterised by C16S, A66C and C117V mutations, where an intrachain disulphide bond is also formed between C83 and the substituted cysteine at 66, was prepared as the N-Phe 140 residue structure as above and as the N-Met-FGF1 (141-amino acid form) by the Frederick National Laboratory for Cancer Research, Biopharmaceutical Development Program, and supplied to Trefoil through a CRADA collaboration with the NCATS TRND program. Both derivatives are annotated as the 140-residue sequence (Jaye et al. 1986). TTHX1001 has the most sensitive cysteine at 117 (Ortega et al. 1991) replaced while TTHX1114 has no free thiols.
Related Knowledge Centers
- Cystine
- Disulfide
- Enzyme
- Genetic Code
- Protein
- Proteinogenic Amino Acid
- Chemical Formula
- Thiol
- E Number
- Zwitterion