scholarly journals Phytic Acid Protects against 6-Hydroxydopamine-Induced Dopaminergic Neuron Apoptosis in Normal and Iron Excess Conditions in a Cell Culture Model

2011 ◽  
Vol 2011 ◽  
pp. 1-6 ◽  
Author(s):  
Qi Xu ◽  
Anumantha G. Kanthasamy ◽  
Manju B. Reddy
Keyword(s):  
Dna Fragmentation ◽  
Phytic Acid ◽  
Caspase 3 ◽  
Fold Increase ◽  
Iron Chelator ◽  
Culture Model ◽  
A Cell ◽  
Induced Apoptosis ◽  
6 Hydroxydopamine ◽  
Stress Dependent

Iron may play an important role in Parkinson's disease (PD) since it can induce oxidative stress-dependent neurodegeneration. The objective of this study was to determine whether the iron chelator, phytic acid (IP6) can protect against 6-hydroxydopamine- (6-OHDA-) induced apoptosis in immortalized rat mesencephalic dopaminergic cells under normal and iron-excess conditions. Caspase-3 activity was increased about 6-fold after 6-OHDA treatment (compared to control; ) and 30 μmol/L IP6 pretreatment decreased it by 38% (). Similarly, a 63% protection () against 6-OHDA induced DNA fragmentation was observed with IP6 pretreatment. Under iron-excess condition, a 6-fold increase in caspase-3 activity () and a 42% increase in DNA fragmentation () with 6-OHDA treatment were decreased by 41% () and 27% (), respectively, with 30 μmol/L IP6. Together, our data suggest that IP6 protects against 6-OHDA-induced cell apoptosis in both normal and iron-excess conditions, and IP6 may offer neuroprotection in PD.

scholarly journals Cytokine regulation of human intestinal primary epithelial cell susceptibility to Fas-mediated apoptosis

2002 ◽  
Vol 282 (1) ◽  
pp. G92-G104 ◽  
Author(s):  
Carla A. Martin ◽  
Asit Panja
Keyword(s):  
Epithelial Cell ◽  
Caspase 3 ◽  
Fold Increase ◽  
Intermediate Form ◽  
Intestinal Epithelial ◽  
Epithelial Cell Apoptosis ◽  
Initiator Caspases ◽  
Ifn Γ ◽  
Induced Apoptosis ◽  
Factor Α

The regulatory mechanisms of nontransformed intestinal epithelial cell apoptosis have not been thoroughly investigated. We determined the susceptibility and mechanism of Fas-mediated apoptosis in nontransformed human intestinal epithelial cells (HIPEC) in the presence and absence of inflammatory cytokines. Despite ample expression of Fas, HIPEC were relatively insensitive to Fas-mediated apoptosis in that agonist anti-Fas antibody (CH11) induced a <25% increase in HIPEC apoptosis. Pretreatment of HIPEC with interferon (IFN)-γ, but not tumor necrosis factor-α or granulocyte-macrophage colony-stimulating factor, significantly increased CH11-induced apoptosis of these cells without increasing Fas expression. Increased apoptosis correlated with increased caspase 3 activation but not expression of procaspase 3. Also, there was a significant delay in the onset of Fas-mediated apoptosis in HIPEC, which correlated with the generation of an activated caspase 3 p22/20 subunit. HIPEC required both initiator caspases 8 and 9 activity but expressed significantly less of the zymogen form of these caspases than did control cells. IFN-γ-mediated sensitization of HIPEC occurred upstream of caspase 9 activation and correlated with a small increase in procaspase 8 expression (<1-fold increase) and a significant increase in expression of an intermediate form (p35) of caspase 4 (3.3-fold increase).

Polyamines are required for activation of c-Jun NH2-terminal kinase and apoptosis in response to TNF-α in IEC-6 cells

2003 ◽  
Vol 285 (5) ◽  
pp. G980-G991 ◽  
Author(s):  
Sujoy Bhattacharya ◽  
Ramesh M. Ray ◽  
Mary Jane Viar ◽  
Leonard R. Johnson
Keyword(s):  
Cytochrome C ◽  
Dna Fragmentation ◽  
Caspase 3 ◽  
Specific Inhibitor ◽  
Cell Types ◽  
Caspase 9 ◽  
Cytochrome C Release ◽  
Tnf Α ◽  
Induced Apoptosis ◽  
Jnk Activation

Intracellular polyamine homeostasis is important for the regulation of cell proliferation and apoptosis and is necessary for the balanced growth of cells and tissues. Polyamines have been shown to play a role in the regulation of apoptosis in many cell types, including IEC-6 cells, but the mechanism is not clear. In this study, we analyzed the mechanism by which polyamines regulate the process of apoptosis in response to tumor necrosis factor-α (TNF-α). TNF-α or cycloheximide (CHX) alone did not induce apoptosis in IEC-6 cells. Significant apoptosis was observed when CHX was given along with TNF-α, as indicated by a significant increase in the detachment of cells, caspase-3 activity, and DNA fragmentation. Polyamine depletion by treatment with α-difluoromethylornithine significantly reduced the level of apoptosis, as judged by DNA fragmentation and the caspase-3 activity of attached cells. Apoptosis in IEC-6 cells was accompanied by the activation of upstream caspases-6, -8, and -9 and NH2-terminal c-Jun kinase (JNK). Inhibition of JNK activation prevented caspase-9 activation. Polyamine depletion prevented the activation of JNK and of caspases-6, -8, -9, and -3. SP-600125, a specific inhibitor of JNK activation, prevented cytochrome c release from mitochondria, JNK activation, DNA fragmentation, and caspase-9 activation in response to TNF-α/CHX. In conclusion, we have shown that polyamine depletion delays and decreases TNF-α-induced apoptosis in IEC-6 cells and that apoptosis is accompanied by the release of cytochrome c, the activation of JNK, and of upstream caspases as well as caspase-3. Polyamine depletion prevented JNK activation, which may confer protection against apoptosis by modulation of upstream caspase-9 activation.

Hypersensitivity of mtDNA-depleted cells to staurosporine-induced apoptosis: roles of Bcl-2 downregulation and cathepsin B

2011 ◽  
Vol 300 (5) ◽  
pp. C1090-C1106 ◽  
Author(s):  
Guillaume Rommelaere ◽  
Sébastien Michel ◽  
Ludovic Mercy ◽  
Antoine Fattaccioli ◽  
Catherine Demazy ◽  
...  
Keyword(s):  
Cell Death ◽  
Cytochrome C ◽  
B Cell ◽  
Dna Fragmentation ◽  
Cathepsin B ◽  
Caspase 3 ◽  
B Cell Lymphoma ◽  
Parental Cell Line ◽  
Induced Apoptosis ◽  
Parp 1

We show that mitochondrial DNA (mtDNA)-depleted 143B cells are hypersensitive to staurosporine-induced cell death as evidenced by a more pronounced DNA fragmentation, a stronger activation of caspase-3, an enhanced poly(ADP-ribose) polymerase-1 (PARP-1) cleavage, and a more dramatic cytosolic release of cytochrome c. We also show that B-cell CLL/lymphoma-2 (Bcl-2), B-cell lymphoma extra large (Bcl-XL), and myeloid cell leukemia-1 (Mcl-1) are constitutively less abundant in mtDNA-depleted cells, that the inhibition of Bcl-2 and Bcl-XL can sensitize the parental cell line to staurosporine-induced apoptosis, and that overexpression of Bcl-2 or Bcl-XL can prevent the activation of caspase-3 in ρ0143B cells treated with staurosporine. Moreover, the inactivation of cathepsin B with CA074-Me significantly reduced cytochrome c release, caspase-3 activation, PARP-1 cleavage, and DNA fragmentation in mtDNA-depleted cells, whereas the pan-caspase inhibitor failed to completely prevent PARP-1 cleavage and DNA fragmentation in these cells, suggesting that caspase-independent mechanisms are responsible for cell death even if caspases are activated. Finally, we show that cathepsin B is released in the cytosol of ρ0 cells in response to staurosporine, suggesting that the absence of mitochondrial activity leads to a facilitated permeabilization of lysosomal membranes in response to staurosporine.

scholarly journals 6-Hydroxydopamine-induced Apoptosis Is Mediated via Extracellular Auto-oxidation and Caspase 3-dependent Activation of Protein Kinase Cδ

2005 ◽  
Vol 281 (9) ◽  
pp. 5373-5382 ◽  
Author(s):  
Katharine Hanrott ◽  
Louise Gudmunsen ◽  
Michael J. O'Neill ◽  
Susan Wonnacott
Keyword(s):  
Protein Kinase ◽  
Caspase 3 ◽  
Induced Apoptosis ◽  
6 Hydroxydopamine ◽  
Protein Kinase Cδ

Mushroom lectin protects arsenic induced apoptosis in hepatocytes of rodents

2010 ◽  
Vol 30 (4) ◽  
pp. 307-317 ◽  
Author(s):  
Tanmoy Rana ◽  
Asit Kumar Bera ◽  
Subhashree Das ◽  
Debasis Bhattacharya ◽  
Diganta Pan ◽  
...  
Keyword(s):  
Dna Fragmentation ◽  
Phagocytic Activity ◽  
Caspase 3 ◽  
Arsenic Exposure ◽  
Terminal Deoxynucleotidyl Transferase ◽  
Proliferation Index ◽  
No Production ◽  
Chronic Arsenic Exposure ◽  
Induced Apoptosis ◽  
Mushroom Lectin

Acute and chronic arsenic exposure result in toxicity both in human and animal beings and cause many hepatic and renal manifestations. The present study stated that mushroom lectin prevents arsenic-induced apoptosis. Apoptosis was measured by morphological alterations, cell proliferation index (CPI), phagocytic activity (nitro blue tetrazolium index; NBT), nitric oxide (NO) production, terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay, DNA fragmentation and caspase-3 activity. Arsenic exposure at 5 μM in the form of sodium arsenite resulted in significant elevation of deformed cells, NO production, TUNEL stained nuclei of hepatocytes, DNA fragmentation and caspase-3 activity. But the CPI and NBT index were significantly declined in arsenic-treated hepatocytes. The beneficial effect of mushroom lectin at 10 μg/mL, 20 μg/mL and 50 μg/mL) showed increased CPI and phagocytic activity. Mushroom lectin at those concentrations reduced deformed cells, NO production, DNA fragmentation and caspase-3 activity of hepatocytes. But significant better protection was observed in 50 μg/mL mushroom lectin-treated hepatocytes. This finding may be of therapeutic benefit in people suffering from chronic arsenic exposure.

Myc-mediated apoptosis is blocked by ectopic expression of Bcl-2

1993 ◽  
Vol 13 (4) ◽  
pp. 2432-2440
Author(s):  
A J Wagner ◽  
M B Small ◽  
N Hay
Keyword(s):  
Cell Cycle ◽  
Growth Factors ◽  
Dna Fragmentation ◽  
Ectopic Expression ◽  
Fold Increase ◽  
Live Cells ◽  
Protective Mechanism ◽  
Potent Inducer ◽  
Induced Apoptosis ◽  
Cell Growth And Proliferation

The product of the c-myc proto-oncogene is an important positive regulator of cell growth and proliferation. Recently, c-Myc has also been demonstrated to be a potent inducer of apoptosis when expressed in the absence of serum or growth factors. To further examine Myc-induced apoptosis, we coexpressed the proto-oncogene bcl2, which has been shown to block apoptosis in other systems, with c-myc in serum-deprived Rat 1a fibroblasts. Here we report that ectopic expression of bcl2 specifically blocks apoptosis induced by constitutive c-myc expression. Constitutive c-myc expression in serum-deprived Rat 1a cells caused a > 15-fold increase in the number of dead cells, accompanied by DNA fragmentation. However, coexpression of bcl2 with c-myc in these cells led to a 10-fold increase in the number of live cells and a significant decrease in DNA fragmentation. Thus, Bcl-2 effectively inhibits Myc-induced apoptosis in serum-deprived Rat 1a fibroblasts without blocking entry into the cell cycle. These results imply that apoptosis serves as a protective mechanism to prevent tumorigenicity elicited by deregulated Myc expression. This protective mechanism is abrogated, however, by Bcl-2 and therefore may explain the synergism between Myc and Bcl-2 observed in certain tumor cells.

scholarly journals Myc-mediated apoptosis is blocked by ectopic expression of Bcl-2.

1993 ◽  
Vol 13 (4) ◽  
pp. 2432-2440 ◽  
Author(s):  
A J Wagner ◽  
M B Small ◽  
N Hay
Keyword(s):  
Cell Cycle ◽  
Growth Factors ◽  
Dna Fragmentation ◽  
Ectopic Expression ◽  
Fold Increase ◽  
Live Cells ◽  
Protective Mechanism ◽  
Potent Inducer ◽  
Induced Apoptosis ◽  
Cell Growth And Proliferation

The product of the c-myc proto-oncogene is an important positive regulator of cell growth and proliferation. Recently, c-Myc has also been demonstrated to be a potent inducer of apoptosis when expressed in the absence of serum or growth factors. To further examine Myc-induced apoptosis, we coexpressed the proto-oncogene bcl2, which has been shown to block apoptosis in other systems, with c-myc in serum-deprived Rat 1a fibroblasts. Here we report that ectopic expression of bcl2 specifically blocks apoptosis induced by constitutive c-myc expression. Constitutive c-myc expression in serum-deprived Rat 1a cells caused a > 15-fold increase in the number of dead cells, accompanied by DNA fragmentation. However, coexpression of bcl2 with c-myc in these cells led to a 10-fold increase in the number of live cells and a significant decrease in DNA fragmentation. Thus, Bcl-2 effectively inhibits Myc-induced apoptosis in serum-deprived Rat 1a fibroblasts without blocking entry into the cell cycle. These results imply that apoptosis serves as a protective mechanism to prevent tumorigenicity elicited by deregulated Myc expression. This protective mechanism is abrogated, however, by Bcl-2 and therefore may explain the synergism between Myc and Bcl-2 observed in certain tumor cells.

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