Disease relevance of TNFAIP1

• Dietary cobalamin (Cbl; vitamin B12) deficiency resulted in severe growth retardation in rats, and body weight in the Cbl-deficient rats at 20 wk of age was significantly lower compared with the age-matched Cbl-sufficient control rats [1].
• These results suggest that B61 is an autocrine growth factor for melanomas but not normal melanocytes [2].
• Expression and regulation of Eck and its cognate ligand B61 were analyzed in the human colonic adenocarcinoma cell line Caco-2 [3].
• Shaky-leg syndrome and vitamin B12 deficiency [4].
• Homocystinuria and megaloblastic anemia responsive to vitamin B12 therapy. An inborn error of metabolism due to a defect in cobalamin metabolism [5].

Psychiatry related information on TNFAIP1

• Highest yields were associated with EEGs, thyroid function studies, vitamin B12 and folate levels, and the Minnesota Multiphasic Personality Inventory [6].
• Even in industrialized nations, deficiencies of folic acid and vitamin B12 are not uncommon and are exacerbated by some therapeutic agents and by substance abuse [7].
• Serum cobalamin (vitamin B12) levels were analyzed retrospectively in 17 patients with primary degenerative dementia and 11 with specific demonstrable causes of dementia (secondary dementia) [8].
• B12 deficiency in presenile dementia [9].
• Vitamin B12 and folate levels and lithium administration in patients with affective disorders [10].

High impact information on TNFAIP1

• New B12 coenzyme-dependent enzymes that catalyzed intermediate steps in the anaerobic conversion of lysine to fatty acids and ammonia were isolated from C. sticklandii and characterized [11].
• These structures reveal that the B12 cofactor undergoes a major conformational change on binding to the apoenzymes of methionine synthase and methylmalonyl-coenzyme A mutase: The dimethylbenzimidazole ligand to the cobalt is displaced by a histidine residue from the protein [12].
• The best-characterized B12-dependent mutases that catalyze carbon skeleton rearrangement, for which methylmalonyl-coenzyme A mutase is the prototype, also bind cobalamin cofactors with histidine as the cobalt ligand, although other cobalamin-dependent mutases do not appear to utilize histidine ligation [12].
• CONCLUSIONS: Treatment with a combination of folic acid, vitamin B12, and pyridoxine significantly reduces homocysteine levels and decreases the rate of restenosis and the need for revascularization of the target lesion after coronary angioplasty [13].
• METHODS: A combination of folic acid (1 mg), vitamin B12 (400 microg), and pyridoxine (10 mg)--referred to as folate treatment--or placebo was administered to 205 patients (mean [+/-SD] age, 61+/-11 years) for six months after successful coronary angioplasty in a prospective, double-blind, randomized trial [13].

Chemical compound and disease context of TNFAIP1

• This provides preliminary evidence that atypical bronchial squamous metaplasia may be reduced by supplementation with folate and vitamin B12 [14].
• Benefits are expected through the improvement of folate and homocysteine status, but there is also a risk of masking or precipitating clinical manifestations related to vitamin B12 deficiency with increasing exposure to folic acid [15].
• Letter: Ascorbic acid and vitamin B12 deficiency [16].
• Urinary methylmalonic acid to detect vitamin B12 deficiency [17].
• Combined therapy with high doses of prednisone and tetracycline hydrochloride resulted in weight gain, cessation of diarrhea, improved absorption of water, fat, and vitamin B12, and production of gastric acid after stimulation with histamine [18].

Biological context of TNFAIP1

• The rat TNFAIP1 gene is mapped to chromosome 10q25 cM, spans approximately 12.9 kb, and is composed of seven exons [19].
• The open reading frame of B12 predicts a 316-amino acid sequence rich in charged residues, particularly at the carboxyl terminus, and has neither significant homology to other known proteins nor to any extent sequence motifs [20].
• B12 is found to be a highly conserved single-copy gene which is located in the q22----q23 region of human chromosome 17 [20].
• Transcript expression is found to be developmentally regulated in a tissue-specific manner, with B12 message being differentially expressed in the heart and liver during mouse embryogenesis [20].
• Protein B61 as a new growth factor: expression of B61 and up-regulation of its receptor epithelial cell kinase during melanoma progression [2].

Anatomical context of TNFAIP1

• Expression of a B61-immunoglobulin chimera showed that B61 could act as an angiogenic factor in vivo and a chemoattractant for endothelial cells in vitro [21].
• Immunoprecipitation of metabolically labeled human umbilical vein endothelial cell preparations revealed that B61 is a 25-kilodalton secreted protein which is markedly induced by tumor necrosis factor [22].
• Growth of normal melanocytes was not affected. mRNA for B61 was detected in both melanoma cell lines and normal melanocytes [2].
• Our data suggest that B61 plays pivotal roles in organogenesis, especially vasculogenesis/angiogenesis and epithelial cell proliferation/differentiation [23].
• In the developing nervous system, expression of B61 is restricted in the neurons of dorsal root ganglia [23].

Associations of TNFAIP1 with chemical compounds

• Role of B61, the ligand for the Eck receptor tyrosine kinase, in TNF-alpha-induced angiogenesis [21].
• There was no evidence of methylmalonic aciduria or deficiency of folate or vitamin B12 [5].
• METHODS: To test this hypothesis, we assessed the effects of breakfast cereals fortified with three levels of folic acid, and also containing the recommended dietary allowances of vitamins B6 and B12, in a randomized, double-blind, placebo-controlled, crossover trial in 75 men and women with coronary artery disease [24].
• Two brothers 62 and 70 years old, without evidence of vitamin B12 lack, excreted 12 to 115 mg of methylmalonic acid daily (normal, less than 9 mg per day) [25].
• These children have no evidence of a deficiency of vitamin B12, which acts as a cofactor with methylmalonyl-CoA mutase, and they did not respond to the administration of vitamin B12 [26].

Regulatory relationships of TNFAIP1

• The B12 protein is further shown to be induced in human umbilical vein endothelial cells by TNF, and the protein is shown to be rapidly degraded [20].

Other interactions of TNFAIP1

• Both CRYAB and TNFAIP1 show increased transcript levels in AD brains, supporting the validity of this approach [27].
• The deduced proteins of rat PDIP1 and rat TNFAIP1 share 63.1% sequence identity with each other and are highly conserved in the majority of the middle portion of the two proteins, which encode a BTB/POZ domain at the N-terminus and a PCNA binding motif (QTKV-EFP) at the C-terminus, respectively [19].
• MNCs from obese subjects have higher IKBKB expression, increased nuclear factor kappa B (NFkappaB) binding and higher mRNA expression of TNFAIP1 and IL6 genes [28].

Analytical, diagnostic and therapeutic context of TNFAIP1

• Sequence analysis of cDNA clones encoding B61 revealed that its protein product has no significant homology to previously described proteins [22].
• B61 was also identified by Western blotting and ECK binding activity with the use of a BIAcore binding assay in melanoma cell-conditioned media [2].
• Examination of B61 mRNA expression by in situ hybridization analysis revealed tight association of B61 with endothelial cells at an early stage and epithelial cells in various tissues including lung, kidney, intestine, skin at later stage of organogenesis [23].
• The results should not be construed as pointing to a potential way of preventing lung cancer in individuals who continue to smoke or as supporting self-medication with large doses of folate or B12 by smokers [14].
• Two sandwich immunoassays were evaluated, one which used the mAb G5 for capture, the other which used B12 for capture [29].

References