Disease relevance of ARID4B

• High expression of RBP1L1 messenger RNA was found in human breast, lung, colon, pancreatic, and ovarian cancers and in normal testis, but expression was limited in other normal tissues [1].
• RBP1L1, a retinoblastoma-binding protein-related gene encoding an antigenic epitope abundantly expressed in human carcinomas and normal testis [1].
• We have purified an mSin3A complex from K562 erythroleukemia cells and identified three new mSin3A-associated proteins (SAP): SAP180, SAP130, and SAP45 [2].
• Benign breast disease sera showed moderate BCAA increases (mean = 48 ng/ml) in 20 of 35 (57%) patients [3].
• BCAA were found to be elevated in 31 of 46 (67%) Group I (mean = 70 ng/ml), 41 of 43 (95%) Group II (mean = 197 ng/ml), and 30 of 46 (65%) Group III (mean = 50 ng/ml) patients' sera, as compared to "background" levels in malignant melanoma and normal controls [3].

Psychiatry related information on ARID4B

• The results indicate that ingestion of BCAA reduces the perceived exertion and mental fatigue during exercise and improves cognitive performance after the exercise [4].
• Based on the responses of testosterone, DHEAs, and cortisol, and on the training-induced increase in BCAA, there appeared to be hormonal and metabolic adaptation despite the inherent psychological stress of competition [5].

High impact information on ARID4B

• SAP180 has two repression domains: a C-terminal domain, which interacts with the mSin3A-HDAC complex, and an N-terminal domain, which functions independently of mSin3A-HDAC [2].
• Use of monoclonal antibodies (Mc 3 and Mc 8) prepared against human mammary-epithelial antigens of human mild fat globule membranes has enabled characterization of breast carcinoma (BC) associated antigens (BCAA), antibodies, and circulating immune complexes (CIC) [3].
• While insulin treatment restores plasma AA pattern, proline, methionine, valine, isoleucine, and total BCAA remain elevated in skeletal muscle intracellular water [6].
• Insulin-dependent diabetes mellitus (IDDM) induces plasma amino acid (AA) abnormalities, including low alanine and high branched-chain (BCAA) [6].
• Rises in plasma glucose tended to be higher in P than NP women, suggesting that insulin's effects on glucose and BCAA uptake may be mediated separately [7].

Chemical compound and disease context of ARID4B

• These results suggest that BCAA ketoacids contribute to cholesterol synthesis in sepsis, as well as being an oxidative source [8].
• In contrast, the clearances of branched-chain AA (BCAA) valine and isoleucine were maintained, and the clearance of leucine was higher (p less than 0.05) in trauma patients with sepsis than in those without [9].
• Twenty-four patients with acute severe pancreatitis were randomised to receive total parenteral nutrition for 7 days with one of two isocaloric (35 kcal/kg/day) and isonitrogenous (0.16 g/kg/day) programmes containing either a low (15.5% w/w (control group)) or a high (57%) content of branched chain amino acids (BCAA (BCAA group)) [10].
• At any AA infusion rate, compared with surviving patients with sepsis (p less than 0.05), patients who developed fatal multiple organ failure syndrome (MOFS) showed increased clearances of all BCAA with further impaired clearance of tyrosine [9].
• The effect of oral glucose, a carbohydrate-rich snack (rice ball), and the BCAA mixture (each, 210 kcal) on RQ was studied in 6 normal subjects and 6 patients with liver cirrhosis after an overnight fast [11].

Biological context of ARID4B

• BRCAA1 protein is composed of 1,214 amino acids with 10 glycosylate sites, and shares 37% amino acid identity and an identical antigen epitope with Rb binding protein 1 [12].
• Exercise without BCAA intake led to a partial phosphorylation of p70 S6 kinase without activating the enzyme, a decrease in Akt phosphorylation, and no change in GSK-3 [13].
• Leucine oxidation increases in proportion to energy expenditure, but the total contribution of BCAA to fuel provision during exercise is minor and insufficient to increase dietary protein requirements [14].
• We have examined the effects of BCAA supplementation on delayed-onset muscle soreness (DOMS) and muscle fatigue induced by squat exercise in humans [15].
• These states are generally characterized by altered BCAA availability (low BCAA intakes, elevated rates of BCAA oxidation, and gluconeogenesis), which are concurrent with activation of proteolysis and suppression of protein synthesis in skeletal muscle and ultimately lead to erosion of lean tissue mass [16].

Anatomical context of ARID4B

• Although there has been great interest in the effects of amino acids on immune function, little is known about the impact of changes in BCAA availability on the ability of the immune system to function [17].
• The BCAA catabolic enzymes are distributed widely in body tissues and, with the exception of the nervous system, all reactions occur in the mitochondria of the cell [18].
• Cell culture studies show that BCAA are absolutely essential for lymphocytes to synthesize protein, RNA, and DNA and to divide in response to stimulation [17].
• Because tyrosine metabolism occurs almost entirely in the liver while leucine can be utilized by viscera and muscle, these data suggest early and progressive septic impairment of the pattern of hepatic uptake and oxidation of AA with a greater body dependence on BCAA, especially leucine, as septic MOFS develops [9].
• In IPD the general trend of Aromatic AA/BCAA ratio suggests a preferential transport of Aromatic AA through the blood brain barrier [19].

Associations of ARID4B with chemical compounds

• This review focuses on the contributions of leucine and the BCAA to regulation of muscle protein synthesis and glycemic control [20].
• BCAA oxidation provides energy for muscle and other organs and is the precursor for amino acid synthesis to replenish alanine and glutamine depleted in catabolic states [21].
• Total BCAA requirement was determined by measuring the oxidation of L-[1-13C] phenylalanine to 13CO2 [F13CO2 in micromol/(kg x h)], after a primed, continuous infusion of the labeled tracer and using a two-phase linear crossover regression analysis [22].
• Cholesterol was directly related to the absolute dose of BCAA (p less than .001), was unrelated to the dose of non-BCAA, and was inversely related to lactate (p less than .001) [8].
• Mean plasma cholesterol for all measurements (2.61 +/- 0.94 [SD] mmol/L) was lower than normal; however, it was higher with 49% BCAA than with 16% BCAA (2.94 +/- 0.95 vs. 2.27 +/- 0.81 mmol/L, p less than .001) for comparable loads of glucose, fat, and total amino acids [8].

Analytical, diagnostic and therapeutic context of ARID4B

• Furthermore, serial sample determination of BCAA in 36 selected BC patients confirmed the above pattern, indicating that this assay can be used with some restriction to monitor tumor burden [3].
• Plasma cholesterol levels, plasma lactate, and total body RQ were measured in septic patients undergoing total parenteral nutrition (TPN) with glucose, fat, and two different branch-chain amino acid admixtures (49% BCAA and 16% BCAA) [8].
• A number of small and diverse clinical trials studied the effects of BCAA-enriched nutritional support in moderately to severely stressed surgical and cancer patients [21].
• The long-term restriction of BCAA intake in diets and orthotopic liver transplantation have proven effective in controlling plasma BCAA levels and mitigating some of the above neurological manifestations [23].
• The data concerning the impact of BCAA supplementation in prophylaxis of long-term morbidity and mortality in patients with cirrhosis is more promising and has been the subject of 2, large randomized controlled trials [24].

References