Apoptotic insults to human HepG2 cells induced by S-(+)-ketamine occurs through activation of a Bax-mitochondria-caspase protease pathway

Lee, S.-T.; Wu, Tsu Tuan; Yu, Ping; Chen, R.-M.

doi:10.1093/bja/aen322

Cited by 77 publications

(63 citation statements)

References 34 publications

(22 reference statements)

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“…The S period is an important indication of cell proliferation, and the proportion of cells in the S period is positively associated with the ability of proliferation (15). We did not observe two typical characteristics of cells undergoing apoptosis, such as the increase of shrinking morphologies and arresting at the sub-G1 phase (16)(17)(18). This result also suggested that total flavonoids from Drynaria fortunei did not induce DPSC toxicity and apoptosis.…”

Section: Discussionmentioning

confidence: 49%

Effects of total flavonoids from Drynaria fortunei on the proliferation and osteogenic differentiation of rat dental pulp stem cells

Huang

Yuan

Yang

2012

Molecular Medicine Reports

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Abstract. Dental pulp stem cells (DPSCs) have the potential to form bone, nerve and fat, and are a candidate for use in regenerative medicine. Previous studies indicated that total flavonoids from Drynaria fortunei show a stimulative effect on the proliferation and osteogenic differentiation of osteoblastic MC3T3-E1 cells in vitro. This study aimed to investigate the effect of total flavonoids from Drynaria fortunei on the proliferation and osteogenic differentiation of rat DPSCs, and to further clarify the mechanisms involved. DPSCs were isolated by enzymatic digestion and identified using the CD44, CD29 and CD34 markers by immunohistochemistry, and exposed to 0.01, 0.05 and 0.1 g/l total flavonoids from Drynaria fortunei media. Total flavonoids from Drynaria fortunei promoted the proliferation of DPSCs in a dose-dependent manner and this effect may depend on the shortening of the G0/G1 phase and promotion of the S phase. Compared with the control group, the levels of alkaline phosphatase (ALP) and the expression of osteogenic genes increased with the concentrations of total flavonoids from Drynaria fortunei, and the volume and number of calcified nodules in the Drynaria groups was bigger compared to the control group. These results suggest that total flavonoid from Drynaria fortunei directly stimulates DPSC proliferation and osteogenic differentiation, and may serve as a new promising candidate drug for dental tissue engineering and bone regeneration.

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Section: Discussionmentioning

confidence: 49%

Effects of total flavonoids from Drynaria fortunei on the proliferation and osteogenic differentiation of rat dental pulp stem cells

Huang

Yuan

Yang

2012

Molecular Medicine Reports

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“…Ketamine-induced apoptosis by mitochondrial pathway has been shown in neuronal cells (Braun et al, 2010;Yon et al, 2005) as well as non-neuronal (lymphocytes and hepatic) cells (Braun et al, 2010;Lee et al, 2009). Acetyl L-carnitine appears to be involved in the restoration of mitochondrial function and/or improved use of energy from glycolysis in cultured neuroblastoma cells treated with the neurotoxicant, 1-methyl-4-phenyl tetrahydropyridine (Mazzio et al, 2003).…”

Section: Discussionmentioning

confidence: 99%

Acetyl l-carnitine protects motor neurons and Rohon-Beard sensory neurons against ketamine-induced neurotoxicity in zebrafish embryos

Cuevas

Trickler

Guo

et al. 2013

Neurotoxicology and Teratology

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Ketamine, a non-competitive antagonist of N-methyl-D-aspartate (NMDA) type glutamate receptors is commonly used as a pediatric anesthetic. Multiple studies have shown ketamine to be neurotoxic, particularly when administered during the brain growth spurt. Previously, we have shown that ketamine is detrimental to motor neuron development in the zebrafish embryos. Here, using both wild type (WT) and transgenic (hb9:GFP) zebrafish embryos, we demonstrate that ketamine is neurotoxic to both motor and sensory neurons. Drug absorption studies showed that in the WT embryos, ketamine accumulation was approximately 0.4% of the original dose added to the exposure medium. The transgenic embryos express green fluorescent protein (GFP) localized in the motor neurons making them ideal for evaluating motor neuron development and toxicities in vivo. The hb9:GFP zebrafish embryos (28 h post fertilization) treated with 2 mM ketamine for 20 h demonstrated significant reductions in spinal motor neuron numbers, while co-treatment with acetyl L-carnitine proved to be neuroprotective. In whole mount immunohistochemical studies using WT embryos, a similar effect was observed for the primary sensory neurons. In the ketamine-treated WT embryos, the number of primary sensory Rohon-Beard (RB) neurons was significantly reduced compared to that in controls. However, acetyl L-carnitine co-treatment prevented ketamine-induced adverse effects on the RB neurons. These results suggest that acetyl L-carnitine protects both motor and sensory neurons from ketamine-induced neurotoxicity.

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“…(28) Briefly, osteoblasts (2 Â 10 4 cells/well) were seeded in 96-well tissue culture plates overnight. After drug treatment, osteoblasts were cultured with new medium containing 0.5 mg/mL of MTT for a further 3 hours.…”

Section: Assay Of Cell Viabilitymentioning

confidence: 99%

GATA-3 transduces survival signals in osteoblasts through upregulation of bcl-x L gene expression

Chen

Lin

Chou

2010

Journal of Bone and Mineral Research

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GATA-3, a transcription factor, participates in regulating cell development, proliferation, and death. This study was aimed at evaluating the roles of GATA-3 in protecting osteoblasts against oxidative stress-induced apoptotic insults and their possible mechanisms. Pretreatment with nitric oxide (NO) for 24 hours protected osteoblasts, prepared from neonatal rat calvaria, against oxidative stressinduced apoptotic insults. Such protection involved enhancement of Bcl-X L messenger (m)RNA and protein syntheses and the translocation of this antiapoptotic protein from the cytoplasm to mitochondria. GATA-3 was detected in rat osteoblasts, and GATA-3-specific DNA-binding elements exist in the promoter region of the bcl-x L gene. NO preconditioning attenuated oxidative stress-caused suppression of GATA-3 mRNA and protein synthesis and the translocation of this transcription factor from the cytoplasm to nuclei. Application of GATA-3 small interfering (si)RNA into osteoblasts decreased the levels of this transcription factor and simultaneously inhibited Bcl-X L mRNA synthesis. Pretreatment with NO lowered the oxidative stress-caused alteration in the binding of GATA-3 to its specific DNA motifs. Oxidative stress-inhibited Runx2 mRNA expression, but NO preconditioning decreased such inhibition. NO pretreatment time-dependently enhanced the association of GATA-3 with Runx2. Knocking down the translation of GATA-3 using RNA interference significantly decreased the protection of NO preconditioning against oxidative stress-induced alterations of cell morphologies, DNA fragmentation, and cell apoptosis. In comparison, overexpression of GATA-3 could promote NO preconditioning-involved Bcl-X L expression and cell survival. Therefore, this study shows that GATA-3 plays critical roles in mediating survival signals in osteoblasts, possibly through upregulating bcl-x L gene expression. ß

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Apoptotic insults to human HepG2 cells induced by S-(+)-ketamine occurs through activation of a Bax-mitochondria-caspase protease pathway

Cited by 77 publications

References 34 publications

Effects of total flavonoids from Drynaria fortunei on the proliferation and osteogenic differentiation of rat dental pulp stem cells

Effects of total flavonoids from Drynaria fortunei on the proliferation and osteogenic differentiation of rat dental pulp stem cells

Acetyl l-carnitine protects motor neurons and Rohon-Beard sensory neurons against ketamine-induced neurotoxicity in zebrafish embryos

GATA-3 transduces survival signals in osteoblasts through upregulation of bcl-x L gene expression

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