Type I cAMP-dependent Protein Kinase Delays Apoptosis in Human Neutrophils at a Site Upstream of Caspase-3

Parvathenani, Lav K.; Buescher, E. Stephen; Chacón-Cruz, Enrique; Beebe, Stephen J.

doi:10.1074/jbc.273.12.6736

Cited by 129 publications

(101 citation statements)

References 39 publications

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“…Melanomas were dissected out of the mouse and frozen in liquid nitrogen. Extracts were prepared from thawed tissue homogenates and assayed for caspase activity using the fluorogenic substrate Ac-DEVD-AFC (Alexis Biochemicals, San Diego, CA) as previously described [20]. This peptide sequence is based on the PARP cleavage site, Asp 216 , for caspases 1, 3, 4, and 7, that exhibits enhanced fluorescence upon cleavage.…”

Section: Determination Of Caspase Activation In Vitromentioning

confidence: 99%

Nanosecond pulsed electric fields cause melanomas to self-destruct

Nuccitelli

Pliquett

Chen

et al. 2006

Biochemical and Biophysical Research Communications

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464

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We have discovered a new, drug-free therapy for treating solid skin tumors. Pulsed electric fields greater than 20 kV/cm with rise times of 30 ns and durations of 300 ns penetrate into the interior of tumor cells and cause tumor cell nuclei to rapidly shrink and tumor blood flow to stop. Melanomas shrink by 90% within two weeks following a cumulative field exposure time of 120 μs. A second treatment at this time can result in complete remission. This new technique provides a highly localized targeting of tumor cells with only minor effects on overlying skin. Each pulse deposits 0.2 J and 100 pulses increase the temperature of the treated region by only 3 °C, ten degrees lower than the minimum temperature for hyperthermia effects. KeywordsSkin cancer; Cancer therapy; Tumor; Pulsed electric fields; Pyknosis; Inhibiting angiogenesis; DNA; Nucleus Electric fields have been employed in several different types of cancer therapy. Some of these involve radiofrequency or microwave devices that heat the tumor to greater than 43 °C to kill the cells via hyperthermia [1,2]. Others use pulsed electric fields to permeabilize the tumor cells to allow the introduction of toxic drugs or DNA [3][4][5]. We have discovered that ultrashort electrical pulses can be used as a purely electrical cancer therapy that kills tumors without hyperthermia or drugs. Previous work from this laboratory found that fibrosarcoma tumors treated in vivo with ten 300 ns pulses exhibited a reduced growth rate compared to control tumors in the same animal [6]. Here, we report that when melanoma tumors are treated with four hundred of these pulses, tumors shrink by 90% within two weeks and a subsequent treatment can result in complete remission.The main characteristics of these nanosecond pulsed electric fields (nsPEF) are their low energy that leads to very little heat production and their ability to penetrate into the cell to permeabilize intracellular organelles [7,8] and release calcium [9][10][11] from the endoplasmic reticulum [11]. They provide a new approach for physically targeting intracellular organelles with many applications, including the initiation of apoptosis in cultured cells [12][13][14] and tumors [6], enhancement of gene transfection efficiency [13,14], and inhibiting tumor growth [6]. During the past year, we have treated over 300 murine melanomas in 120 mice with 40 kV/cm electric field pulses 300 ns in duration with dramatic results. Every tumor exposed to 400 such pulses exhibits rapid pyknosis and reduced blood flow and shrinks by an average of 90% within two The efficacy of this nsPEF treatment depends on two separate electric field parameters: pulse duration and amplitude. The effect of pulse duration can be understood by considering the process of membrane charging when the cell is placed in an electric field. Ions in the cell interior will respond to the electric field by moving in the field direction and charging the highly resistive membrane until they experience no further force. By definition this will only occur ...

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Section: Determination Of Caspase Activation In Vitromentioning

confidence: 99%

Nanosecond pulsed electric fields cause melanomas to self-destruct

Nuccitelli

Pliquett

Chen

et al. 2006

Biochemical and Biophysical Research Communications

Self Cite

464

250

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“…cAMP, however, was also reported to inhibit PI3-K-induced activation of p70S6 kinase in IL-2-responsive cells (63). Specific cell context may be important in the function of PDE3B and cAMP in the action of PKB on cell proliferation/survival, since, in some cells, cAMP actually promotes growth (48,64) and prevents or delays apoptosis (65).…”

Section: Effects Of Pde Inhibitors and Camp On Bad Phosphorylation Anmentioning

confidence: 99%

Cyclic Nucleotide Phosphodiesterase 3B Is a Downstream Target of Protein Kinase B and May Be Involved in Regulation of Effects of Protein Kinase B on Thymidine Incorporation in FDCP2 Cells

Ahmad

Cong

Stenson

et al. 2000

The Journal of Immunology

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Wild-type (F/B), constitutively active (F/B*), and three kinase-inactive (F/Ba−, F/Bb−, F/Bc−) forms of Akt/protein kinase B (PKB) were permanently overexpressed in FDCP2 cells. In the absence of insulin-like growth factor-1 (IGF-1), activities of PKB, cyclic nucleotide phosphodiesterase 3B (PDE3B), and PDE4 were similar in nontransfected FDCP2 cells, mock-transfected (F/V) cells, and F/B and F/B− cells. In F/V cells, IGF-1 increased PKB, PDE3B, and PDE4 activities ∼2-fold. In F/B cells, IGF-1, in a wortmannin-sensitive manner, increased PKB activity ∼10-fold and PDE3B phosphorylation and activity (∼4-fold), but increased PDE4 to the same extent as in F/V cells. In F/B* cells, in the absence of IGF-1, PKB activity was markedly increased (∼10-fold) and PDE3B was phosphorylated and activated (3- to 4-fold); wortmannin inhibited these effects. In F/B* cells, IGF-1 had little further effect on PKB and activation/phosphorylation of PDE3B. In F/B− cells, IGF-1 activated PDE4, not PDE3B, suggesting that kinase-inactive PKB behaved as a dominant negative with respect to PDE3B activation. Thymidine incorporation was greater in F/B* cells than in F/V cells and was inhibited to a greater extent by PDE3 inhibitors than by rolipram, a PDE4 inhibitor. In F/B cells, IGF-1-induced phosphorylation of the apoptotic protein BAD was inhibited by the PDE3 inhibitor cilostamide. Activated PKB phosphorylated and activated rPDE3B in vitro. These results suggest that PDE3B, not PDE4, is a target of PKB and that activated PDE3B may regulate cAMP pools that modulate effects of PKB on thymidine incorporation and BAD phosphorylation in FDCP2 cells.

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“…cAMP has also been reported to inhibit apoptosis upstream of caspase 3 activation in human neutrophils. 231 Several studies have shown that PKA activation results in the phosphorylation of Bad on serine residue 112. 232 This is the same site that is phosphorylated by Raf-1 and Mek and may represent the site upstream of caspase 3 activation that is inhibited by PKA.…”

Section: Pkamentioning

confidence: 99%

Kinases: positive and negative regulators of apoptosis

2000

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Cells sense and respond to extracellular factors via receptors on the cell surface that trigger intracellular signaling pathways. The signals received by the receptors on hematopoietic cells often determine if the cell proliferates, survives or undergoes apoptosis. Apoptosis can be induced by almost any cytotoxic stimuli. These stimuli may be an absence of signals arising from cellular receptors, stimulation of specific ligand receptors on the cell surface, chemotherapeutic agents, and ionizing radiation or oxygen radicals, as well as a number of other factors. Cellular kinases and phosphatases participate in signaling cascades that influence this process. We review the ability of the calmodulin-dependent-kinases, I-B kinases, PI3-kinases, Jakkinases, PKC, PKA, and MAP kinase signaling pathways (Erk, Jnk, and p38), to influence the apoptotic process. In addition, we discuss the cross-talk that exists between signaling cascades that are pro-apoptotic and anti-apoptotic.

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Type I cAMP-dependent Protein Kinase Delays Apoptosis in Human Neutrophils at a Site Upstream of Caspase-3

Cited by 129 publications

References 39 publications

Nanosecond pulsed electric fields cause melanomas to self-destruct

Nanosecond pulsed electric fields cause melanomas to self-destruct

Cyclic Nucleotide Phosphodiesterase 3B Is a Downstream Target of Protein Kinase B and May Be Involved in Regulation of Effects of Protein Kinase B on Thymidine Incorporation in FDCP2 Cells

Kinases: positive and negative regulators of apoptosis

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