Colchicine, a Microtubule Depolymerizing Agent, Inhibits Myocardial Apoptosis in Rats

K, Saji; Fukumoto, Yoshihiro; Suzuki, Jun; Fukui, Shigefumi; Nawata, Jun; Shimokawa, Hiroaki

doi:10.1620/tjem.213.139

Cited by 31 publications

(22 citation statements)

References 41 publications

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“…When the presence of Bcl-2, Bcl-2-Bax heterodimers predominate, which protect cell survival. When Bcl-2 levels are reduced, Bax can form the homodimers, which promote cell death (Ling and Lou 2005;Saji et al 2007). Our results indicated that myocardial ischemia obviously reduced Bcl-2 expression and increased Bax expression, compared with the sham-operated control group.…”

Section: Discussionmentioning

confidence: 99%

Antiapoptotic Mechanisms of Chinese Medicine Formula, Guan-Xin-Er-Hao, in the Rat Ischemic Heart

Zhao

Qin²,

Liu³

et al. 2008

Tohoku J. Exp. Med.

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Considerable evidence indicates that apoptosis plays a critical role in acute myocardial infarction. We have previously shown that Guan-Xin-Er-Hao (GXEH), a Chinese medicine formula, attenuates postischemia myocardial apoptosis. The present study was designed to determine the mechanisms by which GXEH exerts its antiapoptotic effect. Adult male Sprague-Dawley rats were randomized to receive vehicle or GXEH (5 or 15 g/kg) orally 30 min before ischemia and subjected to myocardial ischemia of 3 h (apoptosis peak) or 24 h (necrosis peak) for determination of infarct size. Compared with rats receiving vehicle, those rats treated with GXEH (15 g/kg) showed significantly reduced infarct size, the reduced myocardial apoptosis, as judged by the decreases in TUNEL-positive staining (22.40 ± 5.68% vs. 40.31 ± 10.58%, p < 0.01), and the decrease in the degree of caspase-3 activation (82.97 ± 10.54 vs. 159.95 ± 9.16 μ mol cleaved acetylAsp-Glu-Val-Asp-p-nitroanilide/mg protein, p < 0.01). Treatment with GXEH (15 g/kg) significantly reduced the release of mitochondrial cytochrome c, a primary mediator of apoptosis, the degree of caspase-9 activation, and the Bax/Bcl-2 ratio. Caspase-9 cleaves and activates caspase-3. Bax promotes apoptosis, while Bcl-2 inhibits apoptosis. Thus, the antiapoptotic mechanisms of GXEH may involve the mitochondrial cytochrome cmediated caspase-3 activation in cardiomyocytes after acute myocardial infarction. Taken together, GXEH tilted the balance between Bax and Bcl-2 toward an antiapoptotic state, decreased mitochondrial cytochrome c release, reduced caspase-9 activation, and attenuated subsequent caspase-3 activation and postischemic myocardial apoptosis in rats. GXEH may be used as a promising agent for future treatment of cardiovascular diseases. Traditional Chinese medicine; Guan-Xin-Er-Hao; Apoptosis; Mitochondrial pathway. Tohoku

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Section: Discussionmentioning

confidence: 99%

Antiapoptotic Mechanisms of Chinese Medicine Formula, Guan-Xin-Er-Hao, in the Rat Ischemic Heart

Zhao

Qin²,

Liu³

et al. 2008

Tohoku J. Exp. Med.

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“…This effect may be useful for cancer chemotherapy, but it could also lead to toxic effects in normal cells, such as cardiac cells [16] . However, some studies show increased doxorubicin accumulation in rat cardiomyocytes incubated in doxorubicin in combination with verapamil [18,19] . In another study, inhibition of L-type Ca 2+ channels was implicated in the cardiac depression induced by bupivacaine (marcaine), which causes a stronger arrhythmogenic effect and is probably related to enantiomerspecific binding to Na + or K + channels [20] .…”

Section: Introductionmentioning

confidence: 99%

Oxidative modulation of marcaine and lekoptin in H9C2 rat myoblasts

et al. 2009

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Aim:The cytotoxicity of marcaine was estimated in combination with a calcium channel blocker. In addition, the influence of marcaine and marcaine plus lekoptin on a model system using the H9C2 cardiac cell line was investigated. Methods: Cells were incubated for five hours with marcaine, lekoptin, or with both drugs simultaneously. Apoptotic cells were detected using the TUNEL assay and the alkaline comet assay. Mitochondrial cell function after drug uptake was examined using the MTT assay. The concentration of MDA (malondialdehyde) -the final product of fatty-acid peroxidation, was quantified spectrophotometrically. The expression of glutathione S-transferase π (GST-π) was detected by immunofluorescence (IF) and Western blotting (WB) and inducible nitric oxide synthase (iNOS) was assessed by immunocytochemical staining (ABC). Results: Incubation with marcaine resulted in the highest number of apoptotic cells. After incubation with both marcaine and lekoptin, moderate damage to cells (54.2%±1.775% of DNA destruction) was observed. The highest levels of iNOS and GST-π expression were observed in cells treated with marcaine and marcaine plus lekoptin. The characteristic nuclear GST-π expression was observed in cells treated with both drugs. Conclusion: Lekoptin stimulated cells to proliferate. Marcaine caused membrane damage and ultimately cell death.

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“…Some studies reported that colchicine which could be inhibited apoptosis add to anti-inflammatory effect, reduced the surface expression of Fas. 12,15,16 However, there is no sufficient data about the effect of colchicine on apoptosis in the FMF patients. Boyajyan et al demonstrated less circulating annexin A5 levels which are an apoptotic marker in using regular colchicine patients.…”

Section: Discussionmentioning

confidence: 99%

Serum soluble fas ligand levels in familial Mediterranean fever

Çeri¹,

Unverdi²,

Şeneş³

et al. 2013

Renal Failure

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Introduction: Fas/FasL system plays an important role in the regulation of cell life and death, and circulating levels of sFasL have been shown to increase in some inflammatory conditions. However, there is no sufficient information about the levels of sFasL in patients with FMF. This study was designed to evaluate the serum sFasL levels in patients with FMF during attack and attack-free periods. Methods: Twenty-five FMF patients in attack and forty-four in free-attack period, and 20 age-, sex-, and BMI-matched healthy controls were included in this study. Participants with any chronic diseases were excluded. Blood samples were obtained within the first 24 h of the attack period and between febrile attacks, and levels of WBC, ESR, Fibrinogen, hsCRP and sFasL were determined. Results: The levels of traditional acute phase reactants during the attack were significantly higher than the attack-free and controls (p50.05). The serum sFasL levels in the FMF study groups did not differ from the control group (0.70 AE 0.08 vs. 0.73 AE 0.12; 0.70 AE 0.08 vs. 0.83 AE 0.14; 0.73 AE 0.12 vs. 0.83 AE 0.14, respectively, p40.05). Moreover, the sFasL levels during the attack were not significantly different from those in attack-free patients (0.70 AE 0.08 vs. 0.83 AE 0.14, p40.05). Conclusion: In this study, we demonstrated that serum sFasL levels were not markedly affected in FMF and cannot be used as a supportive marker to differentiate attacks from attack-free periods. However, further studies are needed to determine its usefulness as a marker in clinical practice.

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Colchicine, a Microtubule Depolymerizing Agent, Inhibits Myocardial Apoptosis in Rats

Cited by 31 publications

References 41 publications

Antiapoptotic Mechanisms of Chinese Medicine Formula, Guan-Xin-Er-Hao, in the Rat Ischemic Heart

Antiapoptotic Mechanisms of Chinese Medicine Formula, Guan-Xin-Er-Hao, in the Rat Ischemic Heart

Oxidative modulation of marcaine and lekoptin in H9C2 rat myoblasts

Serum soluble fas ligand levels in familial Mediterranean fever

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