Disease relevance of METHIONINE SULFOXIMINE

• Treatment with MSO in hyperammonemic rats restored the CBF response to hypercapnia (from 73 +/- 8 to 141 +/- 14 ml/min per 100 g) [1].
• Treatment with MSO in hyperammonemic rats did not fully restore the response to hypocapnia but prevented the paradoxical increase in CBF (from 80 +/- 8 to 80 +/- 8 ml/min per 100 g) [1].
• When portacaval anastomosis rats were infused with ammonium acetate and pretreated with 150 mg/kg methionine-sulfoximine, an inhibitor of glutamine synthetase activity, brain edema was ameliorated and intracranial pressure did not rise [2].
• It was hypothesized that deprivation of dietary glutamine leads to intestinal disease that is exacerbated by inhibition of glutamine synthetase by methionine sulfoximine (MS) [3].
• No toxicity is observed upon MSO treatment in the absence of ASNase [4].

High impact information on METHIONINE SULFOXIMINE

• The MSX-induced nuclear localization of GLN3 required the TOR-controlled, type 2A-related phosphatase SIT4 [5].
• We show that the glutamine synthetase inhibitor L-methionine sulfoximine (MSX) specifically provokes glutamine depletion in yeast cells [5].
• Treatment with MSO prevented ammonia-induced increases in intracranial pressure [1].
• Pentobarbital-anesthetized rats treated with either vehicle or MSO (150 mg/kg i.p.) received a 6-hour intravenous infusion of either sodium or ammonium acetate [1].
• In this study, we inhibited the activity of glutamine synthetase with methionine-sulfoximine (MSO) and examined ammonia levels, brain water and CBF [6].

Biological context of METHIONINE SULFOXIMINE

• However, when ARJ cells are treated with both ASNase and L-methionine-sulfoximine (MSO), an inhibitor of GS, no restoration of cell amino acids occurs and the cell population undergoes a typical apoptosis [4].
• Cell growth was stable regardless of MSX concentration [7].
• The highest producer (HP) subclones were isolated from each MSX level by the limiting dilution method and were characterized with respect to antibody production [8].
• RESULTS: The methionine-sulfoximine-inhibited group was found to have lower sucrase-isomaltase activity, a lower density of microvilli, and lower electrical impedance values over time compared with the control group [9].
• Recombinant Chinese hamster ovary (CHO) cells expressing a humanized antibody were obtained by transfection of an antibody expression vector (pKC-GS-HC-huS) into CHO-K1 cells and subsequent glutamine synthetase (GS)-mediated gene amplification in media containing different concentrations of methionine sulfoximine (MSX) [8].

Anatomical context of METHIONINE SULFOXIMINE

• GS was inhibited centrally by perfusing the ventriculocisternal space with artificial cerebrospinal fluid (CSF) containing 92.5 mmol MSO per liter at a fixed pH, perfusion rate, and pressure [10].
• After culturing in the presence of methionine sulfoximine (MSX), a GS inhibitor, we obtained a MSX-resistant HepG2 subline (GS-HepG2), which had amplified GS gene; ammonia removal activity was estimated to be 1/7 of that of rat primary culture hepatocytes [11].
• Caco-2 cells were incubated with different concentrations of Gln with or without methionine sulfoximine (MS, an inhibitor of glutamine synthetase) before stimulation with LPS [12].
• MSO treatment decreased glutamine release from skeletal muscle and plasma glutamine concentration [13].
• An altered transfer of nutrient molecules from astrocytes to neurons may underlie these effects of MS, although direct effects of MS upon neurons or upon peripheral structures that regulate respiration cannot be completely ruled out as an explanation [14].

Associations of METHIONINE SULFOXIMINE with other chemical compounds

• The addition of glutamine to the perfusion medium completely reversed the effects of MSO on calcium-dependent aspartate release [15].
• Inhibition of glutamine synthetase with methionine-sulfoximine resulted in very low hsp expression with glutamate and normal high level expression with glutamine, confirming the importance of glutamine [16].
• Supplemental Gln could rescue cells in hyperoxia from the effect of MSO, suggesting that GS, through the endogenous synthesis of Gln, could attenuate hyperoxic cell injury [17].
• Furthermore, methionine-sulfoximine, which prevented the intracellular glutamine formation from ammonium via inhibition of glutamine synthetase, relieved the inhibition of urea uptake by ammonium [18].
• Association of Mn(II) with brain glutamine synthetase (GS) was assessed under in vivo conditions in the presence of millimolar Mg(II) by trapping bound 54Mn(II) ions in the active site with irreversible inhibitors, namely methionine-sulfoximine (MSOX) or specific analogues thereof plus ATP [19].

Gene context of METHIONINE SULFOXIMINE

• The largest amount of IL-8 was secreted by cells in the presence of MS with no Gln in the medium after exposure to LPS [12].
• Effect of methionine sulfoximine (MSO) on the regional activity of choline acetyltransferase in rat brain [20].

References