Aldolase B attenuates clear cell renal cell carcinoma progression by inhibiting CtBP2 / 医学前沿

Aldolase B (ALDOB), a glycolytic enzyme, is uniformly depleted in clear cell renal cell carcinoma (ccRCC) tissues. We previously showed that ALDOB inhibited proliferation through a mechanism independent of its enzymatic activity in ccRCC, but the mechanism was not unequivocally identified. We showed that the corepressor C-terminal-binding protein 2 (CtBP2) is a novel ALDOB-interacting protein in ccRCC. The CtBP2-to-ALDOB expression ratio in clinical samples was correlated with the expression of CtBP2 target genes and was associated with shorter survival. ALDOB inhibited CtBP2-mediated repression of multiple cell cycle inhibitor, proapoptotic, and epithelial marker genes. Furthermore, ALDOB overexpression decreased the proliferation and migration of ccRCC cells in an ALDOB-CtBP2 interaction-dependent manner. Mechanistically, our findings showed that ALDOB recruited acireductone dioxygenase 1, which catalyzes the synthesis of an endogenous inhibitor of CtBP2, 4-methylthio 2-oxobutyric acid. ALDOB functions as a scaffold to bring acireductone dioxygenase and CtBP2 in close proximity to potentiate acireductone dioxygenase-mediated inhibition of CtBP2, and this scaffolding effect was independent of ALDOB enzymatic activity. Moreover, increased ALDOB expression inhibited tumor growth in a xenograft model and decreased lung metastasis in vivo. Our findings reveal that ALDOB is a negative regulator of CtBP2 and inhibits tumor growth and metastasis in ccRCC.

Physiological changes in certain test plants under automobile exhaust pollution.

Plants are the only living organisms which have to suffer a lot from automobile exhaust pollution because they remain static at their habitat. But such roadside plants like Nerium indicum Mill., Boerhaavia diffusa L., Amaranthus spinosus L., Cephalandra indica Naud., and Tabemaemontana divaricata L. can easily avoid the effects of air pollution by altering their physiological pathways pertaining to photosynthesis and respiration. Stomatal closure in Boerhaavia, Amaranthus, Cephlandra and stomatal clogging in Nerium and Tabemaemontana help these plants in preventing the entry of poisonous gases. The increased activity of the enzyme Phosphoenol Pyruvate Carboxylase (PEPCase) belonging to C4 pathway helps Nerium and Boerhaavia (both C3 plants) in carbon fixation under stress condition. Photorespiration is favoured in Amaranthus, Cephalandra and Tabernaemontana to compensate for the over production of ATP in them. Owing an inefficient gaseous exchange in Boerhaavia and Tabemaemontana, the activity of Glucose 6--Phosphate Dehydrogenase (G6-PD) also increases for the preferential shift to Pentose Phosphate Pathway to produce excess NADPH+H+ which are likely to re-oxidize by metabolic reactions not linked to electron transport chain.

Effect of protein malnutrition on the glycolytic and glutaminolytic enzyme activity of rat thymus and mesenteric lymph nodes

The activity of important glycolytic enzymes (hexokinase, phosphofructokinase, aldolase, phosphohexoseisomerase, pyruvate kinase and lactate dehydrogenase) and glutaminolytic enzymes (phosphate-dependent glutaminase) was determined in the thymus and mesenteric lymph nodes of wistar rats submited to protein malnutrition (6 percent protein in the diet rather than 20 percent) from conception to 12 weeks after birth. The wet weight (g) of the thymus and mesenteric lymph nodes decreased due to protein malnutrition by 87 percent (from 0.30 + 0.05 to 0.04 + 0.01) and 75 percent (0.40 + 0.04 to 0.10 + 0.02), respectively. The protein content was reduced only in the thymus from 102.3 + 4.4 (control rats) to 72.6 + 6.6 (malnourished rats). The glycolytic enzymes were not affected by protein malnutrition, but the glutaminase activity of the thymus and lymph nodes was reduced by halfing in protein-malnourished rats as compared to controls. This fact may lead to a decrease in the cellularity of the organ and thus in its size, weight and protein content.

Gel chromatographic experiments for studying subunit interaction of aldolase and triose-phosphate isomerase

Aldolase and triose-phosphate isomerase [TPI] were prepared and purified from rabbit skeletal muscle by gel chromatographic methods. Molecular weight determination and subunit interaction were demonstrated by gel filtration experiments. Cross-linking of aldolase subunit and TPI subunit with glutaraldehyde was detected from the elution profile of sephadex G/200 column which equilibrated with known proteins. Chemical interaction of the lysyl residue of aldolase with different inhibitors such as acetyl chloride, benzoyl chloride, chloroacetic acid, acetic anhydride, thiourea, thioacetamide and bromo ethyl acetate can prevent the Schiff's base formation and may induce some conformational changes. These conformational changes near catalytic site of aldolase causing inhibition of its catalytic function