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S M Ashiqul Islam, Christopher Michel Kearney, Erich J Baker
Cystine-stabilized peptides have great utility as they naturally block ion channels, inhibit acetylcholine receptors, or inactivate microbes. However, only a tiny fraction of these peptides has been characterized. Exploration for novel peptides most efficiently starts with the identification of candidates from genome sequence data. Unfortunately, though cystine-stabilized peptides have shared structures, they have low DNA sequence similarity, restricting the utility of BLAST and even more powerful sequence alignment-based annotation algorithms, such as PSI-BLAST and HMMER...
June 13, 2018: Scientific Reports
Shee Chee Ong, Alessia Belgi, Bianca van Lierop, Carlie Delaine, Sofianos Andrikopoulos, Christopher A MacRaild, Raymond S Norton, Naomi L Haworth, Andrea J Robinson, Briony E Forbes
The development of fast-acting and highly stable insulin analogues is challenging. Insulin undergoes structural transitions essential for binding and activation of the insulin receptor (IR), but these conformational changes can also affect insulin stability. Previously, we substituted the insulin A6-A11 cystine with a rigid, non-reducible C=C linkage ("dicarba" linkage). A cis alkene permitted the conformational flexibility of the A-chain N -terminal helix necessary for high affinity IR binding resulting in surprisingly rapid activity in vivo Here, we show that, unlike the rapidly acting LysB28ProB29 insulin analogue (KP insulin), cis dicarba insulin is not inherently monomeric...
June 13, 2018: Journal of Biological Chemistry
Natarajan Vijayasankaran, Sharat Varma, Yi Yang, Steve Meier, Robert Kiss
This manuscript summarizes the effect of certain cell culture medium additives on antibody drug substance coloration and acidic charge variants. It has been shown previously that B-vitamins and iron in the cell culture medium could significantly impact color intensity. In this manuscript, we detail the effect of several other cell culture components that have been shown to impact coloration. It is shown that if cystine is used instead of cysteine in the cell culture medium, coloration was reduced. Hydrocortisone has been shown to reduce coloration and boost specific productivity...
June 8, 2018: Biotechnology Progress
Donald L Granger, Donna M Call
We found that a large inoculum of Cryptococcus gattii cells, when plated on Dulbecco's modified eagle's medium (DMEM) incorporated into agar, died within a few hours provided that DMEM agar plates had been stored in darkness for approximately 3 days after preparation. Standard conditions were developed for quantification of killing. The medium lost its fungicidal activity when exposed to visible light of wave length ∼400 nm. The amount of energy required was estimated at 5.8 × 104 joules @ 550 nm. Liquid DMEM conditioned by incubation over DMEM agar plates stored in darkness was fungicidal...
June 6, 2018: Medical Mycology: Official Publication of the International Society for Human and Animal Mycology
Heike Miess, Beatrice Dankworth, Arvin M Gouw, Mathias Rosenfeldt, Werner Schmitz, Ming Jiang, Becky Saunders, Michael Howell, Julian Downward, Dean W Felsher, Barrie Peck, Almut Schulze
Metabolic reprogramming is a prominent feature of clear cell renal cell carcinoma (ccRCC). Here we investigated metabolic dependencies in a panel of ccRCC cell lines using nutrient depletion, functional RNAi screening and inhibitor treatment. We found that ccRCC cells are highly sensitive to the depletion of glutamine or cystine, two amino acids required for glutathione (GSH) synthesis. Moreover, silencing of enzymes of the GSH biosynthesis pathway or glutathione peroxidases, which depend on GSH for the removal of cellular hydroperoxides, selectively reduced viability of ccRCC cells but did not affect the growth of non-malignant renal epithelial cells...
June 5, 2018: Oncogene
Radharani Benvenutti, Matheus Marcon, Carlos G Reis, Laura R Nery, Camila Miguel, Ana P Herrmann, Monica R M Vianna, Angelo Piato
Background: Parkinson's disease (PD) is the second most common neurodegenerative disorder. In addition to its highly debilitating motor symptoms, non-motor symptoms may precede their motor counterparts by many years, which may characterize a prodromal phase of PD. A potential pharmacological strategy is to introduce neuroprotective agents at an earlier stage in order to prevent further neuronal death. N -acetylcysteine (NAC) has been used against paracetamol overdose hepatotoxicity by restoring hepatic concentrations of glutathione (GSH), and as a mucolytic in chronic obstructive pulmonary disease by reducing disulfide bonds in mucoproteins...
2018: PeerJ
Jack L Arbiser, Michael Y Bonner, Nicole Ward, Justin Elsey, Shikha Rao
BACKGROUND: A link between selenium deficiency and inflammatory skin diseases have been noted by many, but this link is still not well understood. We have previously studied the efficacy of ceramide analogs, based on the fire ant venom Solenopsin A, against our psoriasis animal model. Treatment of animals with solenopsin analogs resulted in significantly improved skin as well as in a coordinate downregulation of selenoproteins, namely Glutathione Peroxidase 4 (GPX4). We thus hypothesize that ferroptosis may be a physiologic process that may protect the skin from both inflammatory and neoplastic processes...
May 28, 2018: Biochimica et Biophysica Acta
Halina Jurkowska, Maria Wróbel
BACKGROUND/AIM: In certain cancers, accumulation of cystathionine has been observed. The present study investigated the effect of cystathionine on astrocytoma (U373) cell proliferation, the activity of γ-cystathionase (CTH) and changes in thiols levels. MATERIALS AND METHODS: The methods used in the study included cytotoxicity assay, crystal violet staining method, CTH activity assay and reverse phase-high performance liquid chromatography (RP-HPLC). RESULTS: The addition of cystathionine to the culture medium resulted in an increase of cystathionine level in U373 cells after 24 h of culture...
June 2018: Anticancer Research
Safia Fatima, Ayesha Hafeez, Aamir Ijaz, Naveed Asif, Afshan Awan, Ambreen Sajid
Classical homocystinuria, also known as cystathionine beta synthase deficiency, is a rare disorder of methionine metabolism, leading to an abnormal accumulation of homocysteine and its metabolites in blood and urine. A young child with homocystinuria is discussed, who presented with behavioral abnormalities, involuntary movement, mental retardation, and decreased vision since birth. The diagnosis of homocystinuria was not made at initial presentation. Subtle phenotypic features with developmental delay and MRI brain finding of bilateral medially dislocated lens, eventually provided the first indication at five years of age...
June 2018: Journal of the College of Physicians and Surgeons—Pakistan: JCPSP
Yuka Kimura, Norihiro Shibuya, Hideo Kimura
BACKGROUND AND PURPOSE: Hydrogen sulfide (H2 S) and polysulfides (H2 Sn ) are signaling molecules that mediate various physiological responses including cytoprotection. Their oxidized metabolite sulfite (SO3 2- ) exists in blood and tissues. However, its physiological role remains unclear. In this study, we investigated the cytoprotective effect of sulfite on neurons against oxidative stress caused by high concentrations of a neurotransmitter glutamate, known as oxytosis. EXPERIMENTAL APPROACH: The endogenous concentrations of sulfite as well as those of cysteine and glutathione (GSH) were measured by high performance liquid chromatography...
May 29, 2018: British Journal of Pharmacology
Alessandro Luciani, Beatrice Paola Festa, Zhiyong Chen, Olivier Devuyst
Cystinosis is a lysosomal storage disease due to inactivating mutations in CTNS, the cystinosin transporter that exports cystine out of lysosomes. The lysosomal accumulation of cystine leads to severe dysfunction of the epithelial cells lining the proximal tubule of the kidney, causing defective endocytosis and massive losses of solutes in the urine. The mechanisms linking lysosomal defect and epithelial dysfunction were unknown, preventing the development of disease-modifying therapies. We recently reported that lysosomal alterations in cystinosis lead to defective autophagic clearance of damaged mitochondria, generating oxidative stress...
May 28, 2018: Autophagy
Paola Krall, Daniela Nualart, Jean Grandy
Nephropatic cystinosis (NC) is a rare disease associated with pathogenic variants in the CTNS gene, with a common variant that consists of a 57kb-deletion involving CTNS. Patients with NC that are treated with cysteamine improve their life quality and expectancy. We report a 12-month-old girl with a poor growth rate since the 4th month of life. She was admitted to the Hospital with acute kidney injury, severe dehydration and metabolic acidosis. She was treated with volume restorative and bicarbonate. Proximal tubulopathy and Fanconi's syndrome was diagnosed...
January 2018: Revista Médica de Chile
S A Adler, R Slizyte, K Honkapää, A-K Løes
Beta-keratin in poultry feathers is a structural protein that is resistant to degradation due to disulfide and hydrogen bonds. Feather meal can be a valuable feed compound if the digestibility can be increased. The objective of the present study was to analyze the effects of chemical, enzymatic, and pressure-thermic treatments for chicken feathers on solubility, in vitro protein digestibility (IVPD), and amino acid composition of solubilized and residual fractions. Two experiments were conducted. In experiment 1, models for solubility and IVPD were developed including the above factors applying a central composite face-centered design...
May 23, 2018: Poultry Science
Sho Kobayashi, Shinji Hamashima, Takujiro Homma, Mami Sato, Ryosuke Kusumi, Shiro Bannai, Junich Fujii, Hideyo Sato
The amino acid transport system xc - is important for maintaining intracellular glutathione levels and extracellular redox balance. The main component of system xc - , xCT, is strongly induced by various stimuli, including oxidative stress and bacterial lipopolysaccharides (LPS) in macrophages. In the present study, we investigated the production of nitric oxide by LPS-stimulated mouse peritoneal macrophages isolated from both xCT-deficient and wild-type mice. After culturing macrophages in the presence of LPS for 24-48 h, nitrite levels in the medium of xCT-deficient macrophages were significantly decreased compared to that of wild-type cells...
May 21, 2018: Nitric Oxide: Biology and Chemistry
Celine J Rocca, Stephanie Cherqui
Cystinosis is an autosomal recessive metabolic disease that belongs to the family of lysosomal storage disorders (LSDs). Initial symptoms of cystinosis correspond to the renal Fanconi syndrome. Patients then develop chronic kidney disease and multi-organ failure due to accumulation of cystine in all tissue compartments. LSDs are commonly characterized by a defective activity of lysosomal enzymes. Hematopoietic stem and progenitor cell (HSPC) transplantation is a treatment option for several LSDs based on the premise that their progeny will integrate in the affected tissues and secrete the functional enzyme, which will be recaptured by the surrounding deficient cells and restore physiological activity...
May 22, 2018: Pediatric Nephrology: Journal of the International Pediatric Nephrology Association
Xiangming Ji, Jun Qian, S M Jamshedur Rahman, Peter J Siska, Yong Zou, Bradford K Harris, Megan D Hoeksema, Irina A Trenary, Chen Heidi, Rosana Eisenberg, Jeffrey C Rathmell, Jamey D Young, Pierre P Massion
Many tumors increase uptake and dependence on glucose, cystine or glutamine. These basic observations on cancer cell metabolism have opened multiple new diagnostic and therapeutic avenues in cancer research. Recent studies demonstrated that smoking could induce the expression of xCT (SLC7A11) in oral cancer cells, suggesting that overexpression of xCT may support lung tumor progression. We hypothesized that overexpression of xCT occurs in lung cancer cells to satisfy the metabolic requirements for growth and survival...
May 23, 2018: Oncogene
I Ruiz-Ascacibar, P Stoll, M Kreuzer, G Bee
Breeding efforts over the last decades altered markedly empty body (EB) composition of pigs. This study aimed to re-evaluate the dynamics of changes in the composition and deposition rate of fat, protein and amino acids (AA) in the EB from birth to 140 kg BW depending on the dietary CP and AA supply in a current pig genotype. In the experiment 66 entire male, 58 castrated and 66 female Swiss Large White pigs were used. From 20 kg BW onwards, they had either ad libitum access to a control (C) diet or a diet (LP) compared to diet C only 80% of CP, lysine, methione+cystine, threonine and tryptophan...
May 23, 2018: Animal: An International Journal of Animal Bioscience
Teruaki Takasaki, Kanako Hagihara, Ryosuke Satoh, Reiko Sugiura
Fingolimod hydrochloride (FTY720) is a first-in-class of sphingosine-1-phosphate (S1P) receptor modulator approved to treat multiple sclerosis by its phosphorylated form (FTY720-P). Recently, a novel role of FTY720 as a potential anticancer drug has emerged. One of the anticancer mechanisms of FTY720 involves the induction of reactive oxygen species (ROS) and subsequent apoptosis, which is largely independent of its property as an S1P modulator. ROS have been considered as a double-edged sword in tumor initiation/progression...
2018: Oxidative Medicine and Cellular Longevity
Benjamin C Ede, Rafal R Asmaro, John P Moppett, Paraskevi Diamanti, Allison Blair
Current therapies for childhood T cell acute lymphoblastic leukemia have increased survival rates to above 85% in developed countries. Unfortunately, some patients fail to respond to therapy and many suffer from serious side effects, highlighting the need to investigate other agents to treat this disease. Parthenolide, a nuclear factor kappa B inhibitor and reactive oxygen species inducer, has been shown to have excellent anti-cancer activity in pediatric leukemia xenografts, with minimal effects on normal hemopoietic cells...
May 17, 2018: Haematologica
J-W Lackmann, K Wende, C Verlackt, J Golda, J Volzke, F Kogelheide, J Held, S Bekeschus, A Bogaerts, V Schulz-von der Gathen, K Stapelmann
Reactive oxygen and nitrogen species released by cold physical plasma are being proposed as effectors in various clinical conditions connected to inflammatory processes. As these plasmas can be tailored in a wide range, models to compare and control their biochemical footprint are desired to infer on the molecular mechanisms underlying the observed effects and to enable the discrimination between different plasma sources. Here, an improved model to trace short-lived reactive species is presented. Using FTIR, high-resolution mass spectrometry, and molecular dynamics computational simulation, covalent modifications of cysteine treated with different plasmas were deciphered and the respective product pattern used to generate a fingerprint of each plasma source...
May 16, 2018: Scientific Reports
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