Browsing by Author "Chiu, Ted H."

Now showing 1 - 2 of 2

Activation of p38 mitogen-activated protein kinase by celecoxib oppositely regulates survivin and gamma-H2AX in human colorectal cancer cells
(2007-07-01)
Hslao, Po-Wen
;
Chang, Chia-Ching
;
Liu, Huel-Fang
;
Tsai, Chuan-Mei
;
Chiu, Ted H.
Cancer cells express survivin that facilitates tumorigenesis. Celecoxib has been shown to reduce human colorectal cancers. However, the role and regulation of survivin by celecoxib in colorectal carcinoma cells remain unclear. Treatment with 40-80 mu M celecoxib for 24 h induced cytotoxicity and proliferation inhibition via a concentration-dependent manner in RKO colorectal carcinoma cells. Celecoxib blocked the survivin protein expression and increased the phosphorylation of H2AX at serine- 193 (gamma-H2AX). The survivin gene knockdown by transfection with a survivin siRNA revealed that the loss of survivin correlated with the expression of gamma-H2AX. Meanwhile, celecoxib increased caspase-3 activation and apoptosis. Celecoxib activated the phosphorylation of p38 mitogen-activated protein (MAP) kinase. The phosphorylated proteins of p38 MAP kinase and gamma-H2AX were observed in the apoptotic cells. SB203580, a specific p38 MAP kinase inhibitor, protected the survivin protein expression and decreased the levels of gamma-H2AX and apoptosis in the celecoxib-exposed cells. The blockade of survivin expression increased the celecoxib-induced cytotoxicity; conversely, overexpression of survivin by transfection with a survivin -expressing vector raised the cancer cell proliferation and resisted the celecoxib-induced cell death. Our results provide for the first time that p38 MAP kinase participates in the down-regulation of survivin and subsequently induces the activation of gamma-H2AX for mediating apoptosis following treatment with celecoxib in human colorectal cancer cells. (c) 2007 Elsevier Inc. All rights reserved.
Modulation of somatosensory evoked potentials during wake-sleep states and spike-wave discharges in the rat
(2006-03-01)
Shaw, Fu-Zen
;
Lee, Su-Ying
;
Chiu, Ted H.
;
生物科技學系
;
Department of Biological Science and Technology
Study Objective: To clarify the cortical evoked responses in the primary somatosensory cortex of the rat under states of waking, slow-wave sleep (SWS), paradoxical sleep (PS), and spike-wave discharges (SWDs), which are associated with absence seizure. Design: Somatosensory evoked potentials (SEPs) in response to single- and paired-pulse stimulations under waking, SWS, PS, and SWDs were compared. SEPs to a single-pulse stimulus with regard to cortical spikes of sleep spindles and SWDs were also evaluated. Participants: Twenty Long Evans rats. Interventions: Single- and paired-pulse innocuous electrical stimulations were applied to the tail of rats with chronically implanted electrodes in the primary somatosensory cortex and neck muscle under waking, SWS, PS, and SWDs. Measurements and Results: SEPs displayed distinct patterns under waking/PS and SWS/SWDs. The short-latency P1-N1 wave of the SEP was severely impeded during SWDs but not in other states, Reduction of the P1-N1 magnitude to the second stimulus of the paired-pulse stimulus for interstimulus intervals of <= 300 milliseconds appeared in waking and PS states, but the decrease occurred only at particular interstimulus intervals under SWS. Interestingly, augmentation was found under SWDs. Moreover, cyclic augmentation of the P1-N1 magnitude was associated with spindle spikes, but cyclic reduction was observed with SWD spikes. Conclusion: Changes in SEPs are not only behavior dependent, but also phase locked onto ongoing brain activity. Distinct short-term plasticity of SEPs during sleep spindles or SWDs may merit further studies for seizure control and tactile information processing.