* 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.
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Overview of noun effects
The noun effects has 1 sense (no senses from tagged texts)
1. effects, personal effects -- (property of a personal character that is portable but not used in
business; "she left some of her personal effects in the house"; "I watched over their effects until
they returned")
Overview of noun effect
The noun effect has 6 senses (first 5 from tagged texts)
1. (101) consequence, effect, outcome, result, event, issue, upshot -- (a phenomenon that follows
and is caused by some previous phenomenon; "the magnetic effect was greater when the rod was
lengthwise"; "his decision had depressing consequences for business"; "he acted very wise after the
event")
2. (11) impression, effect -- (an outward appearance; "he made a good impression"; "I wanted to
create an impression of success"; "she retained that bold effect in her reproductions of the
original painting")
3. (9) effect -- (an impression (especially one that is artificial or contrived); "he just did it
for effect")
4. (2) effect, essence, burden, core, gist -- (the central meaning or theme of a speech or literary
work)
5. (1) effect, force -- ((of a law) having legal validity; "the law is still in effect")
6. effect -- (a symptom caused by an illness or a drug; "the effects of sleep loss"; "the effect of
the anesthetic")
Overview of verb effect
The verb effect has 2 senses (first 2 from tagged texts)
1. (17) effect, effectuate, set up -- (produce; "The scientists set up a shock wave")
2. (3) effect -- (act so as to bring into existence; "effect a change")
--- WordNet end ---