Antioxidant and detoxification network Gene Functional Description GCLC GCLC encodes the catalytic subunit of glutamate-cysteine ligase, the rate-limiting enzyme in glutathione synthesis GCLC GCLM GCLM encodes the modifier subunit of glutamate-cysteine ligase GCLM GSR glutathione reductase, an enzyme that maintains high levels of reduced glutathione in the cytosol GSR GSTM5 encodes glutathione S-transferase mu 5, involved in the detoxification of electrophilic compounds GSTM5 GSTP1 encodes glutathione S-transferase pi 1, which is involved in the detoxification of carcinogens, therapeutic drugs, environmental toxins, and products of oxidative stress GSTP1 TXN TXN encodes thioredoxin, a protein involved in the regulation of cellular redox state and protection against oxidative stress.

Two signals converging into fear acquisition It is a general observation in animals that a cue (conditioned stimulus (CS)) comes to induce fear response when it is repeatedly paired with a noxious stimulus (unconditioned stimulus (US)), such as foot shock. However, it is also known for some time that, if animals are exposed only to the CS without pairing with US, the previously acquired responses will gradually decrease, a phenomenon referred to as fear extinction (R1)

GTP The energy available from GTP hydrolysis is the same as ATP hydrolysis, but GTP is utilized for different purposes than ATP due to the selectivity of specific enzymes. GTP concentrations in cells are on average tenfold lower than the millimolar ATP. GTP is a major regulator of multiple energy-dependent cellular processes of protein synthesis and vesicular trafficking involving endocytosis and autophagy. (R2) Inhibition of IMP to GMP conversion depletes GTP the roles of GTP and GTP-binding proteins in the physiology of the normal pancreatic β-cell have been studied in our laboratory using specific inhibitors of inosine monophosphate dehydrogenase, e.

Cystine transporter SLC7A11 (xCT) The cystine/glutamate antiporter SLC7A11 (also commonly known as xCT) functions to import cystine for glutathione biosynthesis and antioxidant defense and is overexpressed in multiple human cancers. … However, most cancer cells largely depend on the cystine transporter system xc− to import cystine, which is then converted to cysteine in the cytosol through an NADPH-consuming reduction reaction (R3) system x-c consists of two subunits: SLC7A11 and SLC3A2 It also depends in chloride:

Boron both upregulates and inhibits Nrf2 - depends on the dose Our results revealed that low doses of boron (up to 160 mg) had positive effect, while high doses (especially 640 mg) caused negative effect on the development of the kidney. The cellular apoptosis was in a biphasic manner by altering the boron quantities. The low doses regulate the oxidative and enzyme activity in the kidney. The IHC and western blot showed maximum localization of Nrf2 in 80 mg/L BA dose group.

SIFT PolyPhen REVEL The rare exome variant ensemble learner (REVEL) method incorporates recently developed individual prediction tools as features and was trained on recently discovered disease and rare neutral missense variants that did not overlap with the training data for its constituent predictors. We also assembled two large independent test sets of recently discovered pathogenic and benign variants that parallel the likely application of REVEL to newly discovered variants from NGS studies.

Cystine availability regulates mTORC1 signaling Cystine deprivation resulted in a time-dependent reduction of mTORC1 signaling, as evidenced by the gradual decrease in the phosphorylation of p70S6K (T389) and S6 (S235/236), which are downstream effectors of mTORC1 (Fig. 1A). Cystine restriction elevated the level of phospho-eIF2α (S51) and ATF4 (Fig. 1A), major nodes of the ISR signaling. Thus, cystine limitation suppressed mTORC1 and activated the ISR, the two major amino acid sensing pathways in HepG2 cells.

Introduction Vanadium is a widely distributed element, and its biological actions have been studied extensively. The average human diet provides 10–160 mg of V a day, mainly from mushrooms, seafood, black pepper, parsley, fennel seeds, grains, and spinach. (R1) Uptake After entering the bloodstream, V compounds are converted into vanadyl cations, which form complexes with transferrin and ferritin and, less frequently, albumin, hemoglobin, and low molecular weight plasma components (citrate, lactate, and phosphate).

Alleviates Insulin Resistance We revealed for the first time that HFD-caused mitochondrial dysfunction could be reversed by VK2 treatment. VK2 enhanced the mitochondrial function by improving mitochondrial respiratory capacity, increasing mitochondrial biogenesis and the enzymatic activities of mitochondrial complexes through SIRT1 signaling. (R1)

Introduction The enzyme adenosylhomocysteinase (AHCY) is widely found in various organisms, such as bacteria, nematodes, yeast, plants, insects, and vertebrates. In mammals, AHCY plays a crucial role in the reversible conversion of S-adenosylhomocysteine (SAH) into adenosine and L-homocysteine. AHCY is part of the one-carbon metabolic cycle, a fundamental process that facilitates the transfer of one-carbon units for various biological processes like purine and thymidine synthesis, amino acid balance (cysteine, serine, and methionine), cellular redox control, and epigenetic regulation.