5-Aminoimidazole-4-carboxamide riboside induces apoptosis in Jurkat cells, but the AMP-activated protein kinase is not involved

5-Aminoimidazole-4-carboxamide (AICA) riboside, a precursor of purine nucleotide biosynthesis, induces apoptosis in Jurkat cells. Incorporation of AICAriboside into the cells is necessary for this effect since addition of nitrobenzylthioinosine, a nucleoside-transport inhibitor, completely protects Jurkat cells from apoptosis. Adenosine, but not other nucleosides, also protects Jurkat cells from AICAriboside-induced apoptosis. The apoptotic effect is caspase-dependent since caspases 9 and 3 are activated and the caspase inhibitor benzyloxycarbonyl-Val-Ala-Asp-fluoromethylketone (Z-VAD.fmk) blocks apoptosis. Furthermore, AICAriboside induces mitochondrial cytochrome c release. AICAriboside, when phosphorylated to AICAribotide (ZMP), is a specific activator of the AMP-activated protein kinase (AMPK) in certain cell types. However, AICAriboside does not activate AMPK in Jurkat cells. Moreover, 5-iodotubercidin, an inhibitor of AICAriboside phosphorylation, does not inhibit apoptosis in Jurkat cells. These results indicate that AICAriboside induces apoptosis independently of ZMP synthesis and AMPK activation in Jurkat cells.

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Possible role for protein kinase B in the anti-apoptotic effect of prolactin in rat Nb2 lymphoma cells

Journal of Endocrinology ◽

10.1677/joe.0.1670085 ◽

2000 ◽

Vol 167 (1) ◽

pp. 85-92 ◽

Cited By ~ 19

Author(s):

KA Al-Sakkaf ◽

LM Mooney ◽

PR Dobson ◽

BL Brown

Keyword(s):

Protein Kinase ◽

Kinase Inhibitor ◽

Protein Kinase B ◽

Cell Types ◽

Pi3 Kinase ◽

Lymphoma Cells ◽

Nb2 Cells ◽

Apoptotic Effect ◽

General Protein ◽

Induced Apoptosis

Prolactin (PRL) is a mitogen for a number of cell types and its action as a survival factor has recently been demonstrated in Nb2 lymphoma cells. However, the intracellular signalling pathways by which PRL promotes the survival of Nb2 cells is unknown. In previous studies, we have shown that PRL caused the activation of phosphatidylinositol 3-kinase (PI3-kinase) and its association with tyrosine phosphorylated fyn. Protein kinase B (PKB), a serine/threonine kinase, is now known to be a downstream component of the PI3-kinase pathway. The aim of the present study was to examine the effect of PRL on the activation of PKB and to find out whether this has any role on the PRL-induced survival of Nb2 cells. Our studies have revealed the phosphorylation and activation of PKB in PRL-stimulated Nb2 cells. We have also observed, using confocal microscopy, translocation of PKB to the membrane of Nb2 cells in response to PRL. These effects were blocked by the PI3-kinase inhibitor, LY294002 (10 microgram/ml). Apoptosis was induced by the general protein kinase inhibitor, staurosporine (STS; 0.1-1 microM), the synthetic glucocorticoid, dexamethasone (Dex; 100 nM) or ionising radiation by exposing Nb2 cells to X-irradiation (IR; 10 Gy). PRL had no effect on STS-induced apoptosis. On the other hand, PRL (100 ng/ml) inhibited apoptosis induced by Dex or IR; this effect of PRL was reversed by the addition of LY294002 (10 microgram/ml). Furthermore, Western blot analysis using phosphospecific PKB antibody on lysates from PRL-treated Nb2 cells showed that phosphorylation of PKB in response to PRL was inhibited by STS (0.5 microM), but not by Dex (100 nM). These results suggest that the PI3-kinase/PKB pathway may mediate the anti-apoptotic effect of PRL in Nb2 cells.

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Mitochondria play an important role in 17β-estradiol attenuation of H2O2-induced rat endothelial cell apoptosis

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.00413.2006 ◽

2007 ◽

Vol 292 (2) ◽

pp. E585-E593 ◽

Cited By ~ 29

Author(s):

Ailing Lu ◽

Michael Frink ◽

Mashkoor A. Choudhry ◽

William J. Hubbard ◽

Loring W. Rue ◽

...

Keyword(s):

Endothelial Cells ◽

Cell Types ◽

Protective Effects ◽

Caspase 9 ◽

Cytochrome C Release ◽

Potent Inducer ◽

Apoptotic Effect ◽

17Β Estradiol ◽

Induced Apoptosis ◽

Different Cell Types

Studies have shown salutary effects of 17β-estradiol following trauma-hemorrhage on different cell types. 17β-Estradiol also induces improved circulation via relaxation of the aorta and has an anti-apoptotic effect on endothelial cells. Because mitochondria play a pivotal role in apoptosis, we hypothesized that 17β-estradiol will maintain mitochondrial function and will have protective effects against H2O2-induced apoptosis in endothelial cells. Endothelial cells were isolated from rats' aorta and cultured in the presence or absence of H2O2, a potent inducer of apoptosis. In additional studies, endothelial cells were pretreated with 17β-estradiol. Flow cytometry analysis revealed H2O2-induced apoptosis in 80.9% of endothelial cells; however, prior treatment of endothelial cells with 17β-estradiol resulted in an ∼40% reduction in apoptosis. This protective effect of 17β-estradiol was abrogated when endothelial cells were cultured in the presence ICI-182780, indicating the involvement of estrogen receptor (ER). Fluorescence microscopy revealed a 17β-estradiol-mediated attenuation of H2O2-induced mitochondrial condensation. Western blot analysis demonstrated that H2O2-induced cytochrome c release from mitochondrion to cytosol and the activation of caspase-9 and -3 were decreased by 17β-estradiol. These findings suggest that 17β-estradiol attenuated H2O2-induced apoptosis via ER-dependent activation of caspase-9 and -3 in rat endothelial cells through mitochondria.

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The role of AMP-activated protein kinase in quercetin-induced apoptosis of HL-60 cells

Acta Biochimica et Biophysica Sinica ◽

10.1093/abbs/gmu014 ◽

2014 ◽

Vol 46 (5) ◽

pp. 394-400 ◽

Cited By ~ 5

Author(s):

J. Xiao ◽

G. Niu ◽

S. Yin ◽

S. Xie ◽

Y. Li ◽

...

Keyword(s):

Protein Kinase ◽

Induced Apoptosis ◽

Amp Activated Protein Kinase

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Glucose regulates AMP-activated protein kinase activity and gene expression in clonal, hypothalamic neurons expressing proopiomelanocortin: additive effects of leptin or insulin

Journal of Endocrinology ◽

10.1677/joe-06-0080 ◽

2007 ◽

Vol 192 (3) ◽

pp. 605-614 ◽

Cited By ~ 46

Author(s):

Fang Cai ◽

Armen V Gyulkhandanyan ◽

Michael B Wheeler ◽

Denise D Belsham

Keyword(s):

Protein Kinase ◽

Energy Homeostasis ◽

Cell Model ◽

Neuronal Cell ◽

Cell Types ◽

Glucose Sensing ◽

Protein Kinase Activity ◽

Energy Status ◽

Ampk Activity ◽

Amp Activated Protein Kinase

The mammalian hypothalamus comprises an array of phenotypically distinct cell types that interpret peripheral signals of energy status and, in turn, elicits an appropriate response to maintain energy homeostasis. We used a clonal representative hypothalamic cell model expressing proopiomelanocortin (POMC; N-43/5) to study changes in AMP-activated protein kinase (AMPK) activity and glucose responsiveness. We have demonstrated the presence of cellular machinery responsible for glucose sensing in the cell line, including glucokinase, glucose transporters, and appropriate ion channels. ATP-sensitive potassium channels were functional and responded to glucose. The N-43/5 POMC neurons may therefore be an appropriate cell model to study glucose-sensing mechanisms in the hypothalamus. In N-43/5 POMC neurons, increasing glucose concentrations decreased phospho-AMPK activity. As a relevant downstream effect, we found that POMC transcription increased with 2.8 and 16.7 mM glucose. Upon addition of leptin, with either no glucose or with 5 mM glucose, we found that leptin decreased AMPK activity in N-43/5 POMC neurons, but had no significant effect at 25 mM glucose, whereas insulin decreased AMPK activity at only 5 mM glucose. These results demonstrate that individual hypothalamic neuronal cell types, such as the POMC neuron, can have distinct responses to peripheral signals that relay energy status to the brain, and will therefore be activated uniquely to control neuroendocrine function.

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AMP-activated protein kinase activation protects gastric epithelial cells from Helicobacter pylori-induced apoptosis

Biochemical and Biophysical Research Communications ◽

10.1016/j.bbrc.2014.09.028 ◽

2014 ◽

Vol 453 (1) ◽

pp. 13-18 ◽

Cited By ~ 25

Author(s):

Guoqiang Lv ◽

Huanhuan Zhu ◽

Feng Zhou ◽

Zhou Lin ◽

Gang Lin ◽

...

Keyword(s):

Helicobacter Pylori ◽

Protein Kinase ◽

Epithelial Cells ◽

Gastric Epithelial Cells ◽

Kinase Activation ◽

Protein Kinase Activation ◽

Induced Apoptosis ◽

Amp Activated Protein Kinase

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AMPK, MAPK and Bax in the heart: some questions answered

Biochemical Journal ◽

10.1042/bj20080712 ◽

2008 ◽

Vol 412 (2) ◽

pp. e15-e16 ◽

Cited By ~ 2

Author(s):

Vilmante Borutaite

Keyword(s):

Protein Kinase ◽

Mitogen Activated Protein Kinase ◽

Wide Field ◽

Biochemical Journal ◽

Mitogen Activated Protein ◽

Isolated Cardiac Myocytes ◽

And Migration ◽

Induced Apoptosis ◽

Amp Activated Protein Kinase ◽

Rapid Activation

The question of how Bax is activated during apoptosis to perform its role in permeabilization of mitochondrial membranes is intriguing for investigators in the wide field of cell death research. In their paper published in the Biochemical Journal in 2006, Capano and Crompton presented their discovery that simulated ischaemia causes rapid activation of AMPK (AMP-activated protein kinase) which phosphorylates and activates p38 MAPK (mitogen-activated protein kinase) leading to Bax activation and translocation to mitochondria in isolated cardiac myocytes. This was the first report on the molecular mechanism of Bax activation and migration during ischaemia-induced apoptosis in cardiomyocytes.

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Involvement of AMP-activated protein kinase in mediating pyrrolo-1,5-benzoxazepine–induced apoptosis in neuroblastoma cells

Investigational New Drugs ◽

10.1007/s10637-016-0366-3 ◽

2016 ◽

Vol 34 (5) ◽

pp. 663-676 ◽

Cited By ~ 3

Author(s):

Jennifer C. Lennon ◽

Stefania Butini ◽

Giuseppe Campiani ◽

Anne O’Meara ◽

D. Clive Williams ◽

...

Keyword(s):

Protein Kinase ◽

Neuroblastoma Cells ◽

Induced Apoptosis ◽

Amp Activated Protein Kinase

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Nitric Oxide–Induced Apoptosis in Human Leukemic Lines Requires Mitochondrial Lipid Degradation and Cytochrome C Release

Blood ◽

10.1182/blood.v93.7.2342 ◽

1999 ◽

Vol 93 (7) ◽

pp. 2342-2352 ◽

Cited By ~ 101

Author(s):

Alexey Ushmorov ◽

Frank Ratter ◽

Volker Lehmann ◽

Wulf Dröge ◽

Volker Schirrmacher ◽

...

Keyword(s):

Nitric Oxide ◽

Cytochrome C ◽

Mitochondrial Protein ◽

Jurkat Cells ◽

Leukemic Cells ◽

Human Leukemia ◽

Cytochrome C Release ◽

Mitochondrial Functions ◽

Mitochondrial Lipid ◽

Induced Apoptosis

Abstract We have previously shown that nitric oxide (NO) stimulates apoptosis in different human neoplastic lymphoid cell lines through activation of caspases not only via CD95/CD95L interaction, but also independently of such death receptors. Here we investigated mitochondria-dependent mechanisms of NO-induced apoptosis in Jurkat leukemic cells. NO donor glycerol trinitrate (at the concentration, which induces apoptotic cell death) caused (1) a significant decrease in the concentration of cardiolipin, a major mitochondrial lipid; (2) a downregulation in respiratory chain complex activities; (3) a release of the mitochondrial protein cytochrome c into the cytosol; and (4) an activation of caspase-9 and caspase-3. These changes were accompanied by an increase in the number of cells with low mitochondrial transmembrane potential and with a high level of reactive oxygen species production. Higher resistance of the CD95-resistant Jurkat subclone (APO-R) cells to NO-mediated apoptosis correlated with the absence of cytochrome c release and with less alterations in other mitochondrial parameters. An inhibitor of lipid peroxidation, trolox, significantly suppressed NO-mediated apoptosis in APO-S Jurkat cells, whereas bongkrekic acid (BA), which blocks mitochondrial permeability transition, provided only a moderate antiapoptotic effect. Transfection of Jurkat cells with bcl-2 led to a complete block of apoptosis due to the prevention of changes in mitochondrial functions. We suggest that the mitochondrial damage (in particular, cardiolipin degradation and cytochrome c release) induced by NO in human leukemia cells plays a crucial role in the subsequent activation of caspase and apoptosis.

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