M-3M3FBS-Induced Ca^(2+) Movement and Apoptosis in HA59T Human Hepatoma Cells

Liu, Shiuh–Inn; Lin, Ko-Long; Lu, Tung‐Wu; Lu, Yi-Chau; Hsu, Shu-Shong; Tsai, Jeng-Yu; Liao, Wei-Chuan; Huang, Fong-Dee; Chi, Chao-Chuan; Liang, Wei; Tseng, Li‐Ling; Chiang, An‐Jen; Jan, Chung‐Ren

doi:10.4077/cjp.2013.baa091

Cited by 12 publications

(12 citation statements)

References 35 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The study by Chen et al (16) observed the increased calcium influx and apoptosis in SCM1 human gastric cancer cells. Liu et al (17) observed a similar effect in HA59T human hepatoma cells. The modulatory effect of m-3M3FBS on smooth muscle reactivity in lipopolysaccharide-pretreated tissue was reported by Grześk (18).…”

Section: Introductionmentioning

confidence: 71%

Effect of 2,4,6-trimethyl-N-[3-(trifluoromethyl)phenyl]benzene-sulfonamide on calcium influx in three contraction models

et al. 2015

View full text Add to dashboard Cite

2,4,6-Trimethyl--[3-(trifluoromethyl)phenyl]benzenesulfonamide (m-3M3FBS) activates phospholipase C and stimulates apoptosis; however, in smooth muscle cells it may increase the perfusion pressure. The main aim of the present study was to evaluate the physiological effect of direct stimulation of phospholipase C on vascular smooth muscle reactivity using three contraction models. Experiments were performed on the isolated and perfused tail artery of Wistar rats. The contraction force in the present model was measured by an increased level of perfusion pressure with a constant flow. Concentration-response curves (CRCs) obtained for phenylephrine, arg-vasopressin, mastoparan-7 and Bay K8644 presented a sigmoidal association. In comparison to the control curves, CRCs in the presence of m-3M3FBS were significantly shifted to the left except for Bay K8644. Analyses of calcium influx suggest that in the presence of m-3M3FBS the calcium influx from intra- and extracellular calcium stores was significantly higher. The results of the present experiments suggest that m-3M3FBS significantly increases the reactivity of vascular smooth muscle stimulated with metabotropic receptors or G-protein by an increase in calcium influx from intra- and extracellular calcium stores. The current knowledge regarding the apoptotic pathway shows the significance of calcium ions involved in this process, thus, m-3M3FBS may induce apoptosis by an increase of cytoplasmic calcium concentration; however, simultaneously, the use of this mechanism in therapy must be preceded by a molecular modification that eliminates a possible vasoconstriction effect.

show abstract

Section: Introductionmentioning

confidence: 71%

Effect of 2,4,6-trimethyl-N-[3-(trifluoromethyl)phenyl]benzene-sulfonamide on calcium influx in three contraction models

et al. 2015

View full text Add to dashboard Cite

show abstract

“…PLC induces the hydrolysis of the membrane phospholipid phosphatidylinositol 4,5-bisphosphate into intracellular diacylglycerol (DAG) and inositol 1,4,5-trisphosphate (IP 3 ) (6), and modulation of PLC reactivity may alter the cellular response to receptor stimulation. It is possible to directly activate PLC with 2,4,6-trim ethyl-N- [ (12) observed a similar effect in m-3M3FBS pretreated HA59T human hepatoma cells. m-3M3FBS is responsible for the increase in calcium influx from intra-and extracellular calcium stores that activate G-protein-coupled receptors, including α 1 -adrenoceptors and vasopressin receptors, thus stimulating vascular smooth muscle cells.…”

Section: Introductionmentioning

confidence: 79%

2,4,6-Trimethyl-N-[3-(trifluoromethyl)phenyl]benzenesulfonamide increases calcium influx in lipopolisaccharide-pre-treated arteries

Grześk

Szadujkis-Szadurska

Bloch-Bogusławska

et al. 2016

Experimental and Therapeutic Medicine

View full text Add to dashboard Cite

Abstract. It has been demonstrated that 2,4,6-trimethyl-N-[3-(trifluoromethyl)phenyl]benzenesulfonamide (m-3M3FBS) activates phospholipase C (PLC) and stimulates apoptosis in smooth muscle cells, which may increase vascular reactivity. The primary aim of the present study was to evaluate the physiological effects of the direct stimulation of PLC by m-3M3FBS on vascular smooth muscle reactivity in arteries pre-treated with lipopolysaccharides (LPS) as a model of septic shock. Experiments were performed on isolated and perfused tail arteries of Wistar rats. The contraction force in the model was measured by assessing increases in perfusion pressure at a constant flow. Parameters describing the concentration-response curves (CRCs) obtained for phenylephrine and arginine-vasopressin in the presence of LPS confirmed a decrease in vessels reactivity. In comparison with the controls, m-3M3FBS treatment caused a significant increase in LPS-untreated as well as pre-treated arteries. Furthermore, in the presence of m-3M3FBS, calcium influx from intra-as well as extracellular calcium stores was significantly higher for LPS-untreated and pre-treated arteries. The results of the present study suggested that m-3M3FBS significantly increased the reactivity of vascular smooth muscle cells pre-treated with LPS by increasing the calcium influx from intra-and extracellular calcium stores. Further studies investigating this mechanism are required to evaluate whether this pathway may be a potential therapeutic strategy to treat sepsis. IntroductionNitric oxide synthase (NOS) is an enzyme that catalyzes a reaction which generates nitric oxide in two different stages. The first stage is the oxidation of L-arginine to N-omega-hydroxy-L-arginine, which is degraded to L-citrulline in the second stage by NOS and oxygen, and accompanied by the release of nitric oxide from endothelial cells. There are three main types of nitric oxide synthase: NOS-1, -2 and -3. NOS-2 is localized mainly in macrophages, striated heart muscle, liver, vascular smooth muscle or vascular endothelium, and is activated as a response to infection, inflammation or sepsis following the release of pro-inflammatory cytokines, including interleukin (IL)-1, interferon (IFN)-γ or tumor necrosis factor (TNF)-α. The activated enzyme is active for a few h and synthesizes large quantities of nitric oxide (1). Nitric oxide produced by NOS-3 acts predominantly as a regulator of muscle tension in the local regulation of vascular tone. It is also a factor inhibiting the adhesion and aggregation of platelets, as well as angiogenesis. The role of NOS-3 as part of the initiation of NOS-2 activation in the presence of lipopolysaccharides (LPS) has been investigated over the past decade. The first study suggesting that NOS-3 has a role in the generation of NO-associated hyporeactivity during early sepsis was published in 2001 (2,3). A study on isolated animal tissue treated with short acting LPS (~5 h) showed a statistically significant inhibition of NOS-2 expression following blockad...

show abstract

“…The first is that m-3M3FBS may be acting through an off target, non-PLC mechanism. Even though m-3M3FBS has been shown to directly activate PLC, it has also has been documented to increase intracellular calcium levels without activating PLC [49], [50]. Our use of the ortho analog, o-3M3FBS, which does not activate PLC at the 10 µM concentration used in our studies [32], provides a measure of control for the off-target effects of m-3M3FBS because o-3M3FBS exhibits many of the same off-target effects exhibited by m-3M3FBS [51].…”

Section: Discussionmentioning

confidence: 99%

Activation of Phospholipase C Mimics the Phase Shifting Effects of Light on Melatonin Rhythms in Retinal Photoreceptors

et al. 2013

View full text Add to dashboard Cite

Many aspects of retinal photoreceptor function and physiology are regulated by the circadian clocks in these cells. It is well established that light is the primary stimulus that entrains these clocks; yet, the biochemical cascade(s) mediating light’s effects on these clocks remains unknown. This deficiency represents a significant gap in our fundamental understanding of photoreceptor signaling cascades and their functions. In this study, we utilized re-aggregated spheroid cultures prepared from embryonic chick retina to determine if activation of phospholipase C in photoreceptors in the absence of light can phase shift the melatonin secretion rhythms of these cells in a manner similar to that induced by light. We show that spheroid cultures rhythmically secrete melatonin and that these melatonin rhythms can be dynamically phase shifted by exposing the cultures to an appropriately timed light pulse. Importantly, we show that activation of phospholipase C using m-3M3FBS in the absence of light induces a phase delay in photoreceptor melatonin rhythms that mirrors that induced by light. The implication of this finding is that the light signaling cascade that entrains photoreceptor melatonin rhythms involves activation of phospholipase C.

show abstract

M-3M3FBS-Induced Ca^(2+) Movement and Apoptosis in HA59T Human Hepatoma Cells

Cited by 12 publications

References 35 publications

Effect of 2,4,6-trimethyl-N-[3-(trifluoromethyl)phenyl]benzene-sulfonamide on calcium influx in three contraction models

Effect of 2,4,6-trimethyl-N-[3-(trifluoromethyl)phenyl]benzene-sulfonamide on calcium influx in three contraction models

2,4,6-Trimethyl-N-[3-(trifluoromethyl)phenyl]benzenesulfonamide increases calcium influx in lipopolisaccharide-pre-treated arteries

Activation of Phospholipase C Mimics the Phase Shifting Effects of Light on Melatonin Rhythms in Retinal Photoreceptors

Contact Info

Product

Resources

About