Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.3.3.1 (citrate synthase)
 4,488 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

It has been reported that immunosuppressant cyclosporin A or FK506 binds to immunophilins in the cell and that these immunophilins make a complex with molecular chaperones HSP70 or HSP90. Although mizoribine has been used clinically as an immunosuppressant, immunophilins of the agent have not yet been fully understood. We investigated their specific binding proteins using mizoribine affinity column chromatography and porcine kidney cytosols. By increasing mizoribine in the eluant from the column, two major proteins (with molecular masses of 60 and 43 kDa) were detected by SDS-polyacrylamide gel electrophoresis. Based on the amino acid sequence analysis of these proteins, 60- and 43-kDa mizoribine-binding proteins were identified with HSP60 and cytosolic actin, respectively. A considerable amount of actin was also eluted from the affinity column by nucleotides, but a very low quantity of HSP60 was eluted under the same conditions. On the other hand, HSP60 was eluted as a major protein in the eluant that was eluted preferentially, with nucleotide followed by mizoribine. Actin was also detected in the eluant, but the quantity of the protein was very low. These results indicated that HSP60 has high affinity to mizoribine, and the interaction was also observed on surface plasmon resonance analysis. Although HSP60 or GroE facilitated refolding of citrate synthase in vitro, mizoribine interfered with the chaperone activity of HSP60. On different types of mizoribine affinity columns, HSP60 or actin recognized the NH(2) group of mizoribine, and this group may be a functional group of the agent.
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PMID:Mammalian HSP60 is a major target for an immunosuppressant mizoribine. 1057 97

alpha-Crystallin, a major lens protein of approximately 800 kDa with subunits of approximately 20 kDa has previously been shown to act as a chaperone protecting other proteins from stress-induced aggregation. Here it is demonstrated that alpha-crystallin can bind to partially denatured enzymes at 42-43 degrees C and prevent their irreversible aggregation, but cannot prevent loss of enzyme activity. However, the alpha-crystallin-bound enzymes regain activity on interaction with other chaperones. The data indicate that the re-activated enzymes are no longer associated with the alpha-crystallin, and ATP is required for re-activation. When inactive luciferase bound to alpha-crystallin was treated with reticulocyte lysate, a rich source of chaperones, up to 60% of the original luciferase activity could be recovered. Somewhat less re-activation was observed when the alpha-crystallin-bound enzyme was treated with heat-shock protein (HSP)70, HSP40, HSP60 and an ATP-generating system. Similar results were also obtained with citrate synthase. The overall results suggest that alpha-crystallin acts to stabilize denaturing proteins so that they can later be re-activated by other chaperones.
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PMID:alpha-crystallin prevents irreversible protein denaturation and acts cooperatively with other heat-shock proteins to renature the stabilized partially denatured protein in an ATP-dependent manner. 1090 3

Heat shock protein (HSP) expression is an adaptive mechanism against the disruption of cell homeostasis during exercise. Several antioxidant supplementation strategies have been used to enhance tissue protection. In this study, we examined the effects of a redox modulator, alpha-lipoic acid (LA) on HSP responses in six standardbred trotters following intense aerobic exercise. DL-LA supplementation (25 mg kg(-1) d(-1)) for five weeks increased the resting levels of HSP90 (1.02+/-0.155 in control and 1.26+/-0.090 after supplementation in arbitrary units) and the recovery levels of inducible HSP70 (0.89+/-0.056 in control and 1.05+/-0.089 after supplementation in arbitrary units) in skeletal muscle. Furthermore, LA increased skeletal muscle citrate synthase activity at rest and lowered the blood lactate concentration during exercise without any changes in the heart rate. LA had no effect on concentrations of HSP60, HSP25 or GRP75 in skeletal muscle. LA decreased the exercise-induced increases in plasma aspartate aminotransferase and creatine kinase concentrations during recovery. Our results suggest that LA supplementation may enhance tissue protection and increase oxidative capacity of the muscle in horse.
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PMID:alpha-Lipoic acid supplementation enhances heat shock protein production and decreases post exercise lactic acid concentrations in exercised standardbred trotters. 1942 59