Words similar to mtx-induced
Example sentences for: mtx-induced
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To test the hypothesis that MTX-induced cell death requires PLC, the effect of U73122, a specific inhibitor of PLC was examined.
Addition of MTX to fura-2 -loaded BAECs, suspended in a cuvette in normal Ca 2+-containing buffer at 37°C, produced a time-dependent increase in [Ca 2+] i (Fig 1, upper panel ). Addition of either U73122 or U73343, the inactive analog, ~3 min before MTX produced a concentration-dependent inhibition of the change in [Ca 2+] i . U73343 exhibited a 3-fold greater potency compared to U73122 (Fig 1, insets ). Since U73343 has no significant effect on PLC over the concentration range employed [ 14 25 26 27 ] , these results suggest that inhibition of the MTX-induced response is independent of PLC.
Although the cellular mechanisms remain poorly defined, it is now clear that zeiosis is associated with apoptotic cell death (for review [ 24 30 ] ). In static images, the morphological changes associated with apoptosis appear as membrane blebs covering the surface of the cells [ 31 32 33 ] . However, time-lapse images reveal that blebs protrude and retract in a dynamic fashion, a hallmark of zeiosis [ 22 23 ] . Dynamic membrane blebbing appears to involve a dramatic change in the cytoskeleton and may be induced by a caspase-3-mediated cleavage of ROCK-I, a Rho-activated serine/threonine kinase known to stimulate actinomycin-based contractions [ 31 32 33 ] . A similar profile can be seen in the videos of MTX-induced cell death in the presence of U73343 ( Files 2 and 3 ). The cells first lose adhesion to the coverslip, retract and roundup.
Irrespective of the exact mechanism, the experiments reported in the present study are the first to correlate MTX-induced vital dye uptake with alterations in cell morphology.
MTX-induced EB uptake and membrane blebbing in single BAECs.
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