Disease relevance of Mpst

• Cells of a brown Norway (BN) rat Moloney sarcoma (MST) failed to express certain BN alloantigen specificities and bound only about 30-50% the amount of labeled alloantibody bound by normal BN spleen cells [1].
• E. coli C32S Trx, however, did not activate MST [2].
• BN rats immunized subcutaneously with a viral induced tumor (MST) or with a chemical-induced fibrosarcoma (BC5) were donors of immune spleen cells [3].
• We have cloned, by cross-hybridization with the cDNA from rat liver heparan sulfate N-deacetylase/N-sulfotransferase, a protein from a heparin synthesizing mastocytoma derived cell line called MST [4].

High impact information on Mpst

• The identification of the FOXO transcription factors as major and evolutionarily conserved targets of MST1 suggests that MST kinases play important roles in diverse biological processes including cellular responses to oxidative stress and longevity [5].
• Further loss of alloantigens that occurred with prolonged in vitro culture was associated with reduced virulence of MST cells for syngeneic hosts and with increased expression of tumor-associated antigens [1].
• On the other hand, reduced glutathione did not affect MST activity [2].
• Reduced Trx turns on a redox switch for the enzymatic activation of MST, which contributes to the maintenance of cellular redox homeostasis [2].
• Rat 3-mercaptopyruvate sulfurtransferase (MST) contains three exposed cysteines as follows: a catalytic site cysteine, Cys(247), in the active site and Cys(154) and Cys(263) on the surface of MST [2].

Chemical compound and disease context of Mpst

• E. coli C35S Trx, in which Cys(35) was replaced with Ser, formed some adducts with MST and activated MST after treatment with DTT [2].
• Rat Moloney sarcoma cells (MST) were pulsed with 35S-L-methionine for 10 and 60 min and lysed by vortexing in 0.5% deoxycholate, 0.5% NP40, 0.02 M Tris, 0.05 M NaCl, pH 7.5, for 30 sec [6].
• The dissociated cell surface membranes of a rat Moloney sarcoma (MST), derived from a BN rat, were extracted with 2 M KI, with 6 M guanidine thiocyanate, or by papain digestion [7].

Biological context of Mpst

• An active site cysteine residue (Cys246; site of formation of persulfide in catalysis) and an arginine residue (Arg185; substrate binding site) in rhodanese were also conserved in MST [8].
• There is a strong possibility that Cys247 is a catalytic site of MST [9].
• Post-translational regulation of mercaptopyruvate sulfurtransferase via a low redox potential cysteine-sulfenate in the maintenance of redox homeostasis [10].
• Oxidative stress decreases MST activity so as to increase the amount of cysteine, a precursor of thioredoxin or glutathione, and furthermore, these cellular reductants restore the activity [10].
• It is concluded that Arg187 and Arg196 of rat MST are critical residues in determining substrate specificity for mercaptopyruvate [9].

Anatomical context of Mpst

• MST was predominantly localized in proximal tubular epithelium in the kidney, pericentral hepatocytes in the liver, cardiac cells in the heart, and neuroglial cells in the brain [11].
• This immunocytochemical study also found that MST was localized in both mitochondria and cytoplasm [11].
• Also, the growth of BC5 was not affected by MST immune spleen cells cultured for 7 days with MST and/or BC5 [3].
• Complexes were localized in the spleen of tumor-bearing and control rats, but much more in spleens of MST-bearing rats [12].
• These results suggest that the MST-derived enzyme is probably unique to the production of heparin in mast cells [4].

Associations of Mpst with chemical compounds

• Arg187 is suggested to be a binding site of both mercaptopyruvate and thiosulfate in MST [9].
• These findings suggested that there was no nearby cysteine with which to form a disulfide, and mild oxidation of MST resulted in formation of a sulfenate (SO(-)) at Cys(247), which exhibited exceptional stability and a lower redox potential than that of glutathione [10].
• Treatment with dithiothreitol restored modified MST to the original mass [10].
• 3-Mercaptopyruvate sulfurtransferase (MST) (EC 2.8.1.2), a multifunctional enzyme, catalyzes a transsulfuration from mercaptopyruvate to pyruvate in the degradation process of cysteine [10].
• Role of amino acid residues in the active site of rat liver mercaptopyruvate sulfurtransferase. CDNA cloning, overexpression, and site-directed mutagenesis [9].

Regulatory relationships of Mpst

• Further, rhodanese cross-reacts with anti-MST antibody [8].

Other interactions of Mpst

• Conversion of rhodanese to MST was tried by site-directed mutagenesis [8].
• The 3-mercaptopyruvate sulfurtransferase and gamma-cystathionase activities in all the investigated tissues of guinea pig were significantly lower than those in rat [13].

Analytical, diagnostic and therapeutic context of Mpst

• A complete amino acid structure of rat liver mercaptopyruvate sulfurtransferase (MST, EC 2.8.1.2) was determined by sequence analysis of cDNA and purified enzyme [9].
• LEW X BN)F1 cardiac allografts survive 1 wk in unmodified LEW recipients (MST +/- SD = 8.3 +/- 1.2 days) but indefinitely (greater than 100 days) in B rats, produced by 750 R sublethal x-radiation 3 to 4 wk after adult thymectomy and reconstitution with syngeneic bone marrow cells from thymectomized thoracic duct-drained donors [14].
• The unresponsive state is eventually reversed by adoptive transfer of 10(8) spleen cells from nonimmune (MST +/- SD = 27.5 +/- 4.7 days) or alloimmune (MST +/- SD = 21.5 +/- 1.9 days) syngeneic animals [14].
• Wistar-Furth islets, which were UV-irradiated at 850-900 J/m2 and cultured for 24 hr prior to transplantation, did not survive any longer than those in control animals receiving untreated islets (MST 5.5 +/- 1 day) [15].
• The MST for the control group was 9.89 +/- 0.35 days [16].

References