Induction of Apoptosis and Changes in Nuclear G-actin Are Mediated by Different Pathways: The Effect of Inhibitors of Protein and RNA Synthesis in Isolated Rat Hepatocytes

Meijerman, Irma; Blom, W. Marty; Bont, H. J. G. M. De; Mulder, Gerard J.; Nagelkerke, J. Fred

doi:10.1006/taap.1998.8616

Cited by 33 publications

(22 citation statements)

References 32 publications

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“…At molecular level there is an irreversible, but noncovalent binding to the peptide-chain elongation site of the 60S subunit of ribosomes [20] . The inhibition of eukaryotic protein synthesis activity by emetine has been linked to its capacity to induce apoptosis in numerous mammal cell types [15,21,22] . However, it is not yet established whether emetine can induce PCD in E. histolytica parasite.…”

Section: Discussionmentioning

confidence: 99%

Emetine produce Entamoeba histolytica Death by Inducing a Programmed Cell Death

Rojas

Gómez

Shibayama

et al. 2007

American J. of Infectious Diseases

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Amoebiasis is a major public health problem in tropical and subtropical countries. Although a number of antiamoebic agents are used for its treatment and the molecular targets of these drugs have been identified, the biochemical and physiological mechanisms that produce trophozoite death are little known. The present study dates the in vitro induction of programmed cell death (PCD) in E. histolytica by emetine. Morphologically, the emetine incubation reduces cytoplasmic volume, produce nuclear condensation and DNA fragmentation, maintaining the plasma membrane integrity; biochemically, the morphological changes are in concordance with the overproduction of reactive oxygen species inside trophozoites. These results provide the first insight related the cellular mechanisms of emetine action.

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Section: Discussionmentioning

confidence: 99%

Emetine produce Entamoeba histolytica Death by Inducing a Programmed Cell Death

Rojas

Gómez

Shibayama

et al. 2007

American J. of Infectious Diseases

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“…Annexin and PI staining were determined using confocal microscopy and flow cytometry as described previously with modifications (Schutte et al, 1998;Goldberg et al, 1999;Meijerman et al, 1999). Briefly, media were removed, RPTCs washed twice with phosphatebuffered saline (PBS), and incubated in binding buffer (10 mM HEPES, 140 mM NaCl, 5 mM KCl, 1 mM MgCl 2 , and 1.8 mM CaCl 2 , pH 7.4) containing annexin V-FITC (25 g/ml) and PI (25 g/ml) for 10 min.…”

Section: Methodsmentioning

confidence: 99%

Cisplatin-Induced Renal Cell Apoptosis: Caspase 3-Dependent and -Independent Pathways

Cummings

Schnellmann²

2002

J Pharmacol Exp Ther

325

215

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The chemotherapeutic cisplatin causes renal dysfunction and renal proximal tubular cell (RPTC) apoptosis. The goal of these studies was to examine the role of p53, caspase 3, 8, and 9, and mitochondria in the signaling of cisplatin-induced apoptosis. Cisplatin (50 M) produced time-dependent apoptosis in RPTCs, causing cell shrinkage, a 50-fold increase in caspase 3 activity, a 4-fold increase in phosphatidylserine externalization, and 5-and 15-fold increases in chromatin condensation and DNA hypoploidy, respectively. Mitochondrial membrane potential and ATP levels did not change at any time during cisplatin exposure. Caspase 8 and 9 activities also did not increase during treatment. Cisplatin increased nuclear p53 expression 4 h after treatment, preceding both caspase 3 activation and chromatin condensation.Treatment with the p53 inhibitor ␣-2-(2-imino-4,5,6,7-tetrahydrobenzothiazol-3-yl)-1-p-tolylethanone (PFT) before cisplatin exposure inhibited p53 nuclear expression at 4, 8, and 12 h and inhibited phosphatidylserine externalization and caspase 3 activation at 12 h. Neither DEVD-fmk nor ZVAD-fmk inhibited cisplatininduced p53 nuclear expression. Both DEVD-fmk and ZVAD-fmk completely inhibited caspase 3 activity but, like PFT, partially inhibited cisplatin-induced chromatin condensation, annexin V labeling, and DNA hypoploidy after 24 h. These data demonstrate that at least 50% of cisplatin-induced apoptosis in RPTC is mediated by p53 and that p53 activates caspase 3 independently of either caspase 9 or 8 or mitochondrial dysfunction. Furthermore, 50% of cisplatin-induced RPTC apoptosis is independent of p53 and caspases 3, 8, and 9.

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“…Annexin V and PI staining were determined using flow cytometry as described previously (Schutte et al, 1998;Goldberg et al, 1999;Meijerman et al, 1999) with modifications . Briefly, media were removed, RPTC were washed twice with PBS, and incubated in binding buffer (10 mM HEPES, 140 mM NaCl, 5 mM KCl, 1 mM MgCl 2 , 1.8 mM CaCl 2 , pH 7.4) containing annexin V-FITC (25 g/ml) and PI (25 g/ml) for 10 min.…”

Section: Methodsmentioning

confidence: 99%

Role of an Endoplasmic Reticulum Ca²⁺-Independent Phospholipase A₂ in Cisplatin-Induced Renal Cell Apoptosis

Cummings¹,

McHowat²,

Schnellmann³

2003

J Pharmacol Exp Ther

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It has been demonstrated recently that rabbit renal proximal tubule cells (RPTC) express a novel Ca 2ϩ -independent phospholipase A 2 (iPLA 2 ) whose activity localizes to the endoplasmic reticulum (ER-iPLA 2 ) and is similar to group VIB PLA 2 . In this study, the expression of group VIB PLA 2 was examined and the role of ER-iPLA 2 in cisplatin-induced apoptosis was determined. Cisplatin induced both time-and concentration-dependent RPTC apoptosis as determined by p53 nuclear localization, annexin V staining, caspase 3 activity, and chromatin condensation. Inhibition of ER-iPLA 2 with bromoenol lactone (5 M) reduced cisplatin-induced annexin V binding 40%, chromatin condensation 55%, and caspase 3 activity 42%, but had no effect on p53 nuclear localization. Treatment of RPTC with the protein kinase C stimulator phorbol 12-myristate 13-acetate increased the activity of ER-iPLA 2 2-fold and increased cisplatin-induced RPTC apoptosis. These studies demonstrate that group VIB PLA 2 is expressed in RPTC and suggest that RPTC ER-iPLA 2 is the rabbit homolog of group VIB PLA 2 . These data also demonstrate that ER-iPLA 2 acts downstream of p53 and upstream of caspase 3 to mediate cisplatin-induced RPTC apoptosis. Finally, ER-iPLA 2 seems to be regulated by protein kinase C.

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Induction of Apoptosis and Changes in Nuclear G-actin Are Mediated by Different Pathways: The Effect of Inhibitors of Protein and RNA Synthesis in Isolated Rat Hepatocytes

Cited by 33 publications

References 32 publications

Emetine produce Entamoeba histolytica Death by Inducing a Programmed Cell Death

Emetine produce Entamoeba histolytica Death by Inducing a Programmed Cell Death

Cisplatin-Induced Renal Cell Apoptosis: Caspase 3-Dependent and -Independent Pathways

Role of an Endoplasmic Reticulum Ca²⁺-Independent Phospholipase A₂ in Cisplatin-Induced Renal Cell Apoptosis

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Induction of Apoptosis and Changes in Nuclear G-actin Are Mediated by Different Pathways: The Effect of Inhibitors of Protein and RNA Synthesis in Isolated Rat Hepatocytes

Cited by 33 publications

References 32 publications

Emetine produce Entamoeba histolytica Death by Inducing a Programmed Cell Death

Emetine produce Entamoeba histolytica Death by Inducing a Programmed Cell Death

Cisplatin-Induced Renal Cell Apoptosis: Caspase 3-Dependent and -Independent Pathways

Role of an Endoplasmic Reticulum Ca2+-Independent Phospholipase A2 in Cisplatin-Induced Renal Cell Apoptosis

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Role of an Endoplasmic Reticulum Ca²⁺-Independent Phospholipase A₂ in Cisplatin-Induced Renal Cell Apoptosis