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M-3M3FBS-Induced Ca² ⁺ Movement and Apoptosis in HA59T Human Hepatoma Cells.
MedLine Citation:
PMID:  23347013     Owner:  NLM     Status:  In-Data-Review    
Abstract/OtherAbstract:
The effect of 2,4,6-trimethyl-N-(meta-3-trifluoromethyl-phenyl)-benzenesulfonamide (m-3M3FBS), a presumed phospholipase C activator, on cytosolic free Ca² ⁺ concentrations ([Ca² ⁺ ]i ) in HA59T human hepatoma cells is unclear. This study explored whether m-3M3FBS elevated basal [Ca² ⁺ ]i levels in suspended cells by using fura-2 as a Ca² ⁺ -sensitive fluorescent dye. M-3M3FBS at concentrations of 10- 50 μM increased [Ca² ⁺ ]i in a concentration-dependent fashion. The Ca² ⁺ signal was reduced partly by removing extracellular Ca² ⁺ . M-3M3FBS-induced Ca² ⁺ influx was inhibited by nifedipine, econazole, SK&F96365, aristolochic acid, and GF109203X. In Ca² ⁺ -free medium, 50 μM m-3M3FBS pretreatment inhibited the [Ca² ⁺ ]i rise induced by the endoplasmic reticulum Ca² ⁺ pump inhibitor thapsigargin. Conversely, pretreatment with thapsigargin partly reduced m-3M3FBS-induced [Ca² ⁺ ]i rise. Inhibition of inositol 1,4,5-trisphosphate formation with U73122 did not alter m-3M3FBS-induced [Ca² ⁺ ]i rise. At concentrations between 10 and 40 μM m-3M3FBS killed cells in a concentration-dependent manner. The cytotoxic effect of m-3M3FBS was not reversed by prechelating cytosolic Ca² ⁺ with 1,2-bis(2- aminophenoxy)ethane-N,N,N',N'-tetraacetic acid (BAPTA). Annexin V/propidium iodide staining data suggest that m-3M3FBS induced apoptosis in a concentration-dependent manner. M-3M3FBS also increased levels of reactive oxygen species. Together, in human hepatoma cells, m-3M3FBS induced a [Ca² ⁺ ]i rise by inducing phospholipase C-independent Ca² ⁺ release from the endoplasmic reticulum and Ca² ⁺ entry via protein kinase C-sensitive store-operated Ca² ⁺ channels. M-3M3FBS induced cell death that might involve apoptosis via mitochondrial pathways.
Authors:
Shiuh-Inn Liu; Ko-Long Lin; Ti Lu; Yi-Chau Lu; Shu-Shong Hsu; Jeng-Yu Tsai; Wei-Chuan Liao; Fong-Dee Huang; Chao-Chuan Chi; Wei-Zhe Liang; Li-Ling Tseng; An-Jen Chiang; Chung-Ren Jan
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  The Chinese journal of physiology     Volume:  56     ISSN:  0304-4920     ISO Abbreviation:  Chin J Physiol     Publication Date:  2013 Feb 
Date Detail:
Created Date:  2013-01-25     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  7804502     Medline TA:  Chin J Physiol     Country:  China (Republic : 1949- )    
Other Details:
Languages:  eng     Pagination:  xxx     Citation Subset:  IM    
Affiliation:
Department of Surgery, Kaohsiung Veterans General Hospital, Kaohsiung 813, Taiwan, Republic of China.
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