Apoptosis induced by simvastatin in rat vascular smooth muscle cell through Ca2+-calpain and caspase-3 dependent pathway

Cheng, Gang; Jiang, Shan; Xu, Geng; Huang, Jinyu; Ma, Ji; Ying, Shu-qin; Zhu, Lijun

doi:10.1016/s1043-6618(03)00245-7

Cited by 24 publications

(13 citation statements)

References 44 publications

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“…Verapamil-induced apoptosis was observed in rat thymus in vivo and in Chinese hamster ovary cells in vitro (12,13). On the other hand, verapamil alleviated apoptosis induced by angiotensin II in cardiomyocytes (14) and that by simvastatin in vascular smooth muscle cells (15). It was demonstrated that apoptosis was induced by 2 µM verapamil in the ovary cells (13), but not in H9c2 cells, as was shown in our study.…”

Section: Discussionsupporting

confidence: 81%

Effects of Antiarrhythmic Drugs on Apoptotic Pathways in H9c2 Cardiac Cells

et al. 2006

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Abstract. Antiarrhythmic drugs may induce cellular apoptosis in the heart. By using representatives of 5 different categories of antiarrhythmic drugs, that is, pilsicainide, propranolol, nifekalant, verapamil, and amiodarone, we investigated whether these ion channel blockers or β-antagonists affect cardiac apoptosis in cell cultures. Cultured H9c2 cells were treated with the drugs at varying concentrations. To determine the degree of apoptosis, the percentage of hypodiploid cells, mitochondrial transmembrane potential (∆Ψ m ), and activities of caspases were measured quantitatively. At 24 h after administration, only amiodarone induced apoptosis in the H9c2 cells. Amiodarone at a concentration of 14.8 µM or higher decreased ∆Ψ m and activated caspase-2 within 3 h of administration, and it caused the appearance of hypodiploid cells and activation of caspases-3 and -9 at 6 h or later. Thus, amiodarone, but none of the other antiarrhythmic drugs tested, possesses a pro-apoptotic effect, mainly via the mitochondrial pathway, suggesting that this effect is distinct from the blocking action of Na + , K + , and Ca 2+ channels or the β-adrenergic receptor. Furthermore, induction of apoptosis in a dose-dependent manner by amiodarone indicates the importance of monitoring the serum concentration in order to avoid its adverse effects.

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Section: Discussionsupporting

confidence: 81%

Effects of Antiarrhythmic Drugs on Apoptotic Pathways in H9c2 Cardiac Cells

et al. 2006

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“…This phenomenon causes an increase in the intracellular calcium levels in smooth muscle cells because calcineurin inhibits Ca² + release from IP 3 R in these cells. Cheng et al [2003] demonstrated that simvastatin induces apoptosis in smooth muscle cells due to increased intracytoplasmic calcium levels and induces caspase activation, and these effects are responsible for programmed cell death [Krebs, 1998;Sasaki et al, 2007]. Thus, it is possible that myoid cell apoptosis that is caused by tacrolimus treatment could result from the interference of this immunosuppressor, via calcineurin inhibition, with intracellular calcium levels.…”

Section: Discussionmentioning

confidence: 99%

Immunosuppressant Prograf® (Tacrolimus) Induces Histopathological Disorders in the Peritubular Tissue of Rat Testes

Caneguim

Cerri

Spolidório

et al. 2011

Cells Tissues Organs

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Treatment with tacrolimus (FK-506) has been shown to induce a significant decrease in the number of spermatocytes, spermatids, and Sertoli cells. Regarding the importance of the peritubular tissue for the maintenance of Sertoli cells, the integrity of the cellular and extracellular components of the peritubular tissue was evaluated in adult rats that were treated with 1 mg/kg/day of FK-506 for 30 and 60 days. Testicular sections were used for a quantitative analysis of the peritubular cells (PCs) and were submitted to the PAS method. Paraffin sections were submitted to the TUNEL method and to immunohistochemistry for the detection of caspase-3. Several testicular fragments were analyzed under a transmission electron microscope (TEM). A weak PAS reaction was noted in the peritubular tissue of the tacrolimus-treated animals. Next to the damaged peritubular tissue, the Sertoli cell nuclei were absent or dislocated from the basement membrane. In the treated animals, the number of PCs decreased significantly compared to the control animals, and these cells showed apoptotic features, were TUNEL positive, and were caspase-3 immunolabeled. Using the TEM, apoptosis was confirmed in myoid cells; moreover, the thickness and undulation of the basal laminae and an enlargement of the collagen I layer adjacent to the myoid cells was observed. Long-term treatment with the immunosuppressor induced peritubular myoid cell death by apoptosis and disarrangement of the peritubular extracellular layers. Future studies are necessary to confirm whether the structural alterations in the seminiferous epithelium are related to the effect of FK-506 on peritubular tissue.

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“…Consistent with previous results, this experiment showed that AlCl 3 intoxication accompanied the increase of [Ca 2+ ]i in OB. Intracellular Ca 2+ overload causes a series of metabolic disorders and apoptosis [35][36][37]. In this experiment, BAPTA-AM R rescued the decrease of OB apoptosis rate induced by AlCl 3 .…”

Section: Discussionmentioning

confidence: 88%

Aluminum Chloride Induces Osteoblasts Apoptosis via Disrupting Calcium Homeostasis and Activating Ca2+/CaMKII Signal Pathway

Cao

Liu

Zhang

et al. 2015

Biol Trace Elem Res

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Aluminum promotes osteoblast (OB) apoptosis. Apoptosis is induced by the disordered calcium homeostasis. Therefore, to investigate the relationship between Al-induced OB apoptosis and calcium homeostasis, calvarium OBs from neonatal rats (3-4 days) were cultured and exposed to 0.048-mg/mL Al(3+) or 0.048-mg/mL Al(3+) combined with 5 μM BAPTA-AM (OBs were pretreated with 5 μM BAPTA-AM for 1 h, then added 0.048 mg/mL Al(3+)), respectively. Then OB apoptosis rate, intracellular calcium ions concentration ([Ca(2+)]i), mRNA expression level of calmodulin (CaM), and protein expression levels of CaM and p-CaMKII in OBs were examined. The result showed that AlCl3 increased OB apoptosis rate, and [Ca(2+)]i and p-CaMKII expression levels and decreased CaM expression levels, whereas BAPTA-AM relieved the effects. These results proved that AlCl3 induced OB apoptosis by disrupting the intracellular Ca(2+) homeostasis and activating the Ca(2+)/CaMKII signal pathway. Our findings can provide new insights for revealing the apoptosis mechanism of OBs exposed to AlCl3.

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Apoptosis induced by simvastatin in rat vascular smooth muscle cell through Ca2+-calpain and caspase-3 dependent pathway

Cited by 24 publications

References 44 publications

Effects of Antiarrhythmic Drugs on Apoptotic Pathways in H9c2 Cardiac Cells

Effects of Antiarrhythmic Drugs on Apoptotic Pathways in H9c2 Cardiac Cells

Immunosuppressant Prograf® (Tacrolimus) Induces Histopathological Disorders in the Peritubular Tissue of Rat Testes

Aluminum Chloride Induces Osteoblasts Apoptosis via Disrupting Calcium Homeostasis and Activating Ca2+/CaMKII Signal Pathway

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