Apoptosis is Initiated by Myocardial Ischemia and Executed During Reperfusion

Freude, B.; Masters, Thomas N.; Robicsek, Francis; Fokin, Alexander A.; Kostin, Sava; Zimmermann, René; Ullmann, Claudia; Lorenz-Meyer, Silja; Schaper, Jutta

doi:10.1006/jmcc.1999.1066

Cited by 248 publications

(134 citation statements)

References 31 publications

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“…When the cell apoptosis process is disordered, it will become the pathogenesis of many human diseases, including cancer, viral infections, autoimmune diseases, and so on (Thompson, 1995). Meanwhile, apoptosis has an important effect on many CVD (Freude et al, 2000). The apoptosis rates collected by flow cytometry in this paper confirmed that HA+GA might exert a protective effect against OGD-induced apoptosis.…”

Section: Discussionsupporting

confidence: 56%

Protective mechanisms of hypaconitine and glycyrrhetinic acid compatibility in oxygen and glucose deprivation injury

Wang

Wan

Zhou

et al. 2017

J. Zhejiang Univ. Sci. B

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This study investigated the protective effect of the compatibility of hypaconitine (HA) and glycyrrhetinic acid (GA) on H9c2 cells under oxygen and glucose deprivation (OGD)-induced injury, and the possible mechanisms. We found that HA+GA significantly improved pathology and morphology of the nucleus and ultrastructure of H9c2 cells under OGD as determined by Hoechst 33342 staining and transmission electron microscopy (TEM) tests. It also reduced the releases of lactate dehydrogenase (LDH), creatine kinase-myocardial band isoenzyme (CK-MB), and aspartate transaminase (AST) from the cultured supernatant of H9c2 cells, which were tested by enzyme-linked immune sorbent assay (ELISA) kits. In addition, it lessened the apoptotic rate as determined by a fluorescein isothiocyanate-annexin V/propidium iodide (FITC-AV/PI) double staining assay. It was also found that HA+GA might regulate the protein expression associated with the phosphatidylinositol 3-kinase (PI3K)/Akt signaling pathway. Overall, the study demonstrated that HA+GA protected H9c2 cells against OGD-induced injury, and the signaling mechanism might be related to the PI3K/Akt signaling pathway.

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Section: Discussionsupporting

confidence: 56%

Protective mechanisms of hypaconitine and glycyrrhetinic acid compatibility in oxygen and glucose deprivation injury

Wang

Wan

Zhou

et al. 2017

J. Zhejiang Univ. Sci. B

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“…Apoptosis triggered by oxidative stress is an important pathogenic mechanism in I/R-induced cell death [32]. In this study, results of the TUNEL assay demonstrated that the 15 mg/ kg dose of ebselen reduced the apoptotic index.…”

Section: Discussionsupporting

confidence: 49%

Different dose-dependent effects of ebselen in sciatic nerve ischemia-reperfusion injury in rats

et al. 2015

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Ebselen is an organoselenium compound which has strong antioxidant and anti-inflammatory effects. We investigated the neuroprotective role of ebselen pretreatment in rats with experimental sciatic nerve ischemia-reperfusion (I/R) injury. Adult male Sprague Dawley rats were divided into four groups (N = 7 in each group). Before sciatic nerve I/R was induced, ebselen was injected intraperitoneally at doses of 15 and 30 mg/kg. After a 2 h ischemia and a 3 h reperfusion period, sciatic nerve tissues were excised. Tissue levels of malondialdehyde (MDA) and nitric oxide (NO), and activities of superoxide dismutase (SOD), glutathione peroxidase (GPx), and catalase (CAT) were measured. Sciatic nerve tissues were also examined histopathologically. The 15 mg/kg dose of ebselen reduced sciatic nerve damage and apoptosis (P < 0.01), levels of MDA, NO, and inducible nitric oxide synthase (iNOS) positive cells (P < 0.01, P < 0.05, respectively), and increased SOD, GPx, and CAT activities (P < 0.001, P < 0.01, P < 0.05, respectively) compared with the I/R group that did not receive ebselen. Conversely, the 30 mg/kg dose of ebselen increased sciatic nerve damage, apoptosis, iNOS positive cells (P < 0.01, P < 0.05, P < 0.001) and MDA and NO levels (P < 0.05, P < 0.01) and decreased SOD, GPx, and CAT activities (P < 0.05) compared with the sham group. The results of this study suggest that ebselen may cause different effects depending on the dose employed. Ebselen may be protective against sciatic nerve I/R injury via antioxidant and antiapoptotic activities at a 15 mg/kg dose, conversely higher doses may cause detrimental effects.

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“…It is notable that the protective doses of sildenafil used in the present study are 1 and 10 M (ϳ0.69 and 6.9 g/ml, respectively), which are much lower than used to demonstrate the pro-apoptotic effect in the cancer cells (41). Apoptotic cell death has been appreciated as an important component of the pathogenesis of myocardial ischemia-reperfusion injury (42)(43)(44)(45)(46). Our results on sildenafil-induced antiapoptotic effect in cardiomyocytes may have potential therapeutic ramification in chronic ischemic heart diseases and heart failure, where apoptosis serves as the primary driving force for the loss of cardiomyocytes.…”

Section: Effect Of Sildenafil On Bcl-2 Expression In Inos-or Enosdefimentioning

confidence: 83%

Phosphodiesterase-5 Inhibitor Sildenafil Preconditions Adult Cardiac Myocytes against Necrosis and Apoptosis

Das

Xi²,

Kukreja

2005

Journal of Biological Chemistry

323

276

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We investigated the effect of sildenafil in protection against necrosis or apoptosis in cardiomyocytes. Adult mouse ventricular myocytes were treated with sildenafil (1 or 10 M) for 1 h before 40 min of simulated ischemia (SI). Necrosis was determined by trypan blue exclusion and lactate dehydrogenase release following SI alone or plus 1 or 18 h of reoxygenation (RO). Apoptosis was assessed by terminal deoxynucleotidyl transferase-mediated nick end labeling assay and mitochondrial membrane potential measured using a fluorescent probe 5,5 ,6,6 -tetrachloro-1,1 ,3,3 -tetraethylbenzimidazolyl-carbocyanine iodide (JC-1). Sildenafil reduced necrosis as indicated by decrease in trypan blue-positive myocytes and leakage of lactate dehydrogenase compared with untreated cells after either SI or SI-RO. The number of terminal deoxynucleotidyl transferase-mediated nick end labeling-positive myocytes or loss of JC-1 fluorescence following SI and 18 h of RO was attenuated in the sildenafil-treated group with concomitant inhibition of caspase 3 activity. An early increase in Bcl-2 to Bax ratio with sildenafil treatment was also observed in myocytes after SI-RO. The increase of Bcl-2 expression by sildenafil was inhibited by nitric-oxide synthase (NOS) inhibitor, L-nitro-amino-methyl-ester. The drug also enhanced mRNA and protein content of inducible NOS (iNOS) and endothelial NOS (eNOS) in the myocytes. Sildenafil-induced protection against necrosis and apoptosis was absent in the myocytes derived from iNOS knock-out mice and was attenuated in eNOS knock-out myocytes. The up-regulation of Bcl-2 expression by sildenafil was also absent in iNOS-deficient myocytes. Reverse transcription-PCR, Western blots, and immunohistochemical assay confirmed the expression of phosphodiesterase-5 in mouse cardiomyocytes. These data provide strong evidence for a direct protective effect of sildenafil against necrosis and apoptosis through NO signaling pathway. The results may have possible therapeutic potential in preventing myocyte cell death following ischemia/reperfusion.

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Apoptosis is Initiated by Myocardial Ischemia and Executed During Reperfusion

Cited by 248 publications

References 31 publications

Protective mechanisms of hypaconitine and glycyrrhetinic acid compatibility in oxygen and glucose deprivation injury

Protective mechanisms of hypaconitine and glycyrrhetinic acid compatibility in oxygen and glucose deprivation injury

Different dose-dependent effects of ebselen in sciatic nerve ischemia-reperfusion injury in rats

Phosphodiesterase-5 Inhibitor Sildenafil Preconditions Adult Cardiac Myocytes against Necrosis and Apoptosis

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