* Microcystin-LR-caused ROS generation involved in p38 activation and tau hyperphosphorylation in neuroendocrine (PC12) cells.
- Microcystin-LR (MC-LR), a potent specific hepatotoxin produced by cyanobacteria, has recently been reported to show neurotoxicity. Our previous study demonstrated that MC-LR caused the reorganization of cytoskeleton architectures and hyperphosphorylation of the cytoskeletal-associated proteins tau and HSP27 in neuroendocrine PC12 cell line by direct PP2A inhibition and indirect p38 mitogen-activated protein kinase (MAPK) activation. It has been shown that oxidative stress is extensively associated with MC-LR toxicity, mainly resulting from an excessive production of reactive oxygen species (ROS). However, the mechanisms by which ROS mediates the cytotoxic action of MC-LR are unclear. In the present study, we investigated whether ROS might play a critical role in MC-LR-induced hyperphosphorylation of microtubule-associated protein tau and the activation of the MAPKs in PC12 cell line. The results showed that MC-LR had time- and concentration-dependent effects on ROS generation, p38-MAPK activation and tau phosphorylation. The time-course studies indicated similar biphasic changes in ROS generation and tau hyperphosphorylation, which started to increase within 1 h and reached the maximum level at 3 h followed by a decrease after prolonged treatment. Furthermore, pretreatment with the antioxidants, N-acetylcysteine and vitamin C, significantly decreased MC-LR-induced ROS generation and effectively attenuated p38-MAPK activation as well as tau hyperphosphorylation. Taken together, these findings suggest that ROS generation triggered by MC-LR is a key intracellular event that contributes to an induction of p38-MAPK activation and tau phosphorylation, and that blockade of this ROS-mediated redox-sensitive signal cascades may attenuate the toxic effects of MC-LR.
=>1.時代, 季節, 歳月, 当時, 現代, 一生, 年季, 就業時間, 期間, 時刻, 時点, 機会, 拍子, 速度, 何度, 何回,
時, 時間, 回, 2.時間[速度]を測定する, 時間を決める, (装置などの)タイミングを調節する
Overview of noun time
The noun time has 10 senses (first 9 from tagged texts)
1. (219) time, clip -- (an instance or single occasion for some event; "this time he succeeded"; "he
called four times"; "he could do ten at a clip")
2. (160) time -- (a period of time considered as a resource under your control and sufficient to
accomplish something; "take time to smell the roses"; "I didn't have time to finish"; "it took more
than half my time")
3. (114) time -- (an indefinite period (usually marked by specific attributes or activities); "he
waited a long time"; "the time of year for planting"; "he was a great actor in his time")
4. (43) time -- (a suitable moment; "it is time to go")
5. (36) time -- (the continuum of experience in which events pass from the future through the
present to the past)
6. (10) time -- (a person's experience on a particular occasion; "he had a time holding back the
tears"; "they had a good time together")
7. (7) clock time, time -- (a reading of a point in time as given by a clock; "do you know what time
it is?"; "the time is 10 o'clock")
8. (5) fourth dimension, time -- (the fourth coordinate that is required (along with three spatial
dimensions) to specify a physical event)
9. (1) meter, metre, time -- (rhythm as given by division into parts of equal duration)
10. prison term, sentence, time -- (the period of time a prisoner is imprisoned; "he served a prison
term of 15 months"; "his sentence was 5 to 10 years"; "he is doing time in the county jail")
Overview of verb time
The verb time has 5 senses (first 3 from tagged texts)
1. (4) clock, time -- (measure the time or duration of an event or action or the person who performs
an action in a certain period of time; "he clocked the runners")
2. (3) time -- (assign a time for an activity or event; "The candidate carefully timed his
appearance at the disaster scene")
3. (1) time -- (set the speed, duration, or execution of; "we time the process to manufacture our
cars very precisely")
4. time -- (regulate or set the time of; "time the clock")
5. time -- (adjust so that a force is applied and an action occurs at the desired time; "The good
player times his swing so as to hit the ball squarely")
--- WordNet end ---