cAMP-Mediated Signals as Determinants for Apoptosis in Primary Granulosa Cells

Aharoni, Dorit; Dantes, Ada; Oren, Moshe; Amsterdam, Abraham

doi:10.1006/excr.1995.1156

Cited by 137 publications

(78 citation statements)

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“…Elevated levels of intracellular cyclic AMP are known to induce apoptotic cell death in rat leukemia cell lines [14], in rat primary granulosa cells [15], in rat thymocytes [16] and in human B lymphocytes [17]. Here we extend these reports, substantiating that rat renal mesangial cells are susceptible to cyclic AMP-induced apoptosis.…”

Section: Discussionsupporting

confidence: 83%

“…Depending on the cell type cyclic AMP either inhibits or activates extracellular signal regulated kinases and thus either blocks or stimulates cell proliferation by a mechanism which involves protein kinase A-mediated Raf-1 kinase phosphorylation [19]. In a complementary fashion cAMP has been reported to modulate apoptosis in either a positive [14][15][16] or negative way [20,21] by modulating the dynamic balance between two members of the mitogen-activated protein kinase family [20]. Importantly, cAMP has been shown to inhibit [3H]thymidine incorporation into growth factor-activated mesangial cells [22] and attenuates extracelluar signal regulated kinases in response to angiotensin II or platelet-derived growth factor [19].…”

Section: B Ementioning

confidence: 99%

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Apoptosis is triggered by the cyclic AMP signalling pathway in renal mesangial cells

et al. 1996

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Glomerular mesangial cells are regarded as specialized smooth muscle cells located within the renal glomeruli and fulfilling important functions in glomerular physiology and pathophysiology. Here, we report that activation of the cyclic AMP signalling pathway by dibutyryl cyclic AMP, forskolin, or the ~2-adrenergic receptor agonist salbutamol results in induction of apoptosis in mesangial cells. Activation of the apoptotic programme results in DNA fragmentation which is visible for most forms of apoptosis and is paralleled by enrichment of cytosolic DNA/histone complexes, an increasing number of cellular 3'-OH-fragmented DNA ends and typical nuclear chromatin condensation. Induction of apoptosis was found to be dependent on translation and independent of nitric oxide synthase activity.Key words: Apoptosis; Cyclic AMP; Forskolin; Salbutamol; Mesangial cells characterize cellular signals which initiate the apoptotic programme in mesangial cells. Here we present evidence that activation of the cyclic AMP signalling pathway results in mesangial cell apoptosis in a translation-dependent and nitric oxide synthase-independent manner.

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Section: Discussionsupporting

confidence: 83%

Section: B Ementioning

confidence: 99%

Apoptosis is triggered by the cyclic AMP signalling pathway in renal mesangial cells

et al. 1996

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“…Increases in intracellular cAMP, brought about by agents that activate adenylyl cyclase or by cAMP analogues that activate PKA, have been reported to induce apoptosis and/or inhibit proliferation in some cells, including lymphoid cells (41)(42)(43)(44), granulosa cells (45), tumor cells (46 -48), and cultured smooth muscle cells (49). PDE inhibitors, by presumably increasing cAMP, have also been reported to inhibit proliferation/induce apoptosis of lymphoid cells (50 -53), cultured vascular smooth muscle cells (54), and tumor cells (55).…”

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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“…Pharmacological cAMP agonists are also known to be cytotoxic to certain lymphoid lines in vitro [69,70], and agents that elevate cAMP stimulate DNA fragmentation typical of apoptosis in thymocytes [71,72]. More recent work has confirmed these observations [73,74] and extended them to a variety of other model systems, including immortalized primary granulosa cells [75,76], human mammary carcinoma cells [77] and various normal and transformed T and B cells [78,79]. As one would predict, cAMP-induced apoptosis involves activation of cAMP-dependent protein kinase (PKA) [71,80] and specific protein phosphorylation changes [81].…”

Section: Campmentioning

confidence: 99%

Signal Transduction Pathways in Apoptosis

1996

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Abstract. Emerging evidence indicates that apoptosis is regulated by some of the same signal transduction pathways previously implicated in other physiological cellular responses, including alterations in intracellular Ca 2+ compartmentalization, activation of protein kinases and phosphatases, alterations in pH and oxidative stress. Interestingly, signals that promote apoptosis in one model can suppress cell death in another, indicating that cellular responses are determined by the intrinsic programming of the cell in question. This review will summarize current knowledge of the signal transduction pathways regulating apoptosis and discuss how they may be coupled to components of the molecular machinery for cell death.

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cAMP-Mediated Signals as Determinants for Apoptosis in Primary Granulosa Cells

Cited by 137 publications

References 0 publications

Apoptosis is triggered by the cyclic AMP signalling pathway in renal mesangial cells

Apoptosis is triggered by the cyclic AMP signalling pathway in renal mesangial cells

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

Signal Transduction Pathways in Apoptosis

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