Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P42574 (caspase-3)
 45,978 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Human histiocytic lymphoma U937 cells were exposed to continuous 1-MHz ultrasound (US) for therapeutic use, (0 approximately 6.5 W/cm(2) (I(SPTA)). Apoptosis and its related end points were examined by flow cytometry. Fraction of cells with low mitochondria membrane potential were observed after sonication and significant superoxide and peroxide formation, increased activity of caspase-3, and DNA fragmentation revealed biochemically, were also found. The fraction of early apoptosis and secondary necrosis increased with the incubation time after sonication. Early apoptosis observed at 6 h after sonication reached its maximum at 2 min of sonication and gradually decreased. On the other hand, secondary necrosis increased with the duration of sonication. When the effects of dissolved gases, Ar, N(2), O(2), air, N(2)O and CO(2), on free radical formation due to inertial cavitation were investigated by electron spin resonance (ESR) spin trapping, formation of hydroxyl radicals and hydrogen atoms was found in solutions saturated with Ar, N(2), O(2) and air, but not with N(2)O and CO(2). Apoptosis induced by US was also dependent on the dissolved gases in the order Ar = N(2) = O(2) = air >> N(2)O = CO(2) approximately 0. These results suggest that US-induced apoptosis, which is mitochondria-caspase dependent, was linked to inertial cavitation. However, quantities of free radicals did not influence the fraction of early apoptosis and secondary necrosis. When the cells were sonicated in the presence of an echo contrast agent, Levovist; synergistic enhancement of secondary necrosis induced by US was observed at concentrations of more than 20 mg/mL. In contrast, an additive increase of early apoptosis was observed in the combined treatments. These results suggest that Levovist; acting as cavitation nuclei, enhances secondary necrosis induced by US due to an increase in the membrane damage.
 ...
PMID:Effects of dissolved gases and an echo contrast agent on apoptosis induced by ultrasound and its mechanism via the mitochondria-caspase pathway. 1207 4

Recently, we have reported that ultrasound (US)-induced apoptosis is due to inertial cavitation and that extracellular reactive oxygen species (ROS) generated by inertial cavitation are not directly correlated with the apoptosis (Honda et al. 2002). The molecular mechanism of apoptosis induced by US is not yet sufficiently clear. Here, we examine the role of intracellular calcium ions and the intracellular ROS on apoptosis induced by US. Human myelomonocytic lymphoma U937 cells were exposed to continuous 1-MHz US at an intensity of 4.9 W/cm(2) (I(SPTA)) in the presence of air, and changes of intracellular calcium ion concentration ([Ca(2+)]i) in individual cells by digital imaging, various flow cytometric analyses of endpoints of apoptosis (early apoptosis, secondary necrosis, loss of mitochondria membrane potential, superoxide formation, caspase-3 activation) and DNA fragmentation were explored. Furthermore, the effects of an intracellular calcium ion chelator (BAPTA-AM), an antioxidant (N-acetyl-L-cysteine, NAC), a calcium channel blocker (verapamil), Ca(2+)-free buffer and Levovist were also investigated. These results indicate that: 1. the mitochondria-caspase pathway and the Ca(2+)-dependent pathway play cardinal roles in apoptosis induced by US because BAPTA-AM partially inhibited DNA fragmentation, loss of mitochondria membrane potential and caspase-3 activation; 2. intracellular ROS generated from mitochondria, rather than extracellular ROS (which were directly produced by inertial cavitation in the medium), are involved in the regulation of apoptosis induced by US because addition of NAC after sonication showed effective suppression of the apoptosis; and 3. increase of [Ca(2+)]i appears to be due to nonspecific influx from outside the cells because verapamil is not effective and no increase of [Ca(2+)]i due to sonication could be observed in the Ca(2+)-free buffer.
 ...
PMID:Role of intracellular calcium ions and reactive oxygen species in apoptosis induced by ultrasound. 1518 35