Cyclic AMP increases rat inhibitor of apoptosis protein (RIAP1) mRNA in renal mesangial cells

Manderscheid, Markus; Pereda-Fernández, Carmen; Pfeilschifter, Josef

doi:10.1046/j.1523-1755.2002.00223.x

Cited by 7 publications

(4 citation statements)

References 35 publications

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“…Focal adhesion kinase (FAK) has been shown to activate the phosphatidylinositol 3-kinase (PI3K)/Akt survival pathway and NF-B, resulting in upregulation of c-IAP1, c-IAP2, and XIAP in HL 60 cells (49). NF-B also interacts with the cAMP signaling pathway and regulates transcription of IAP expression through the cAMP-responsive elements that are present in the promoter of IAP genes (9,28).…”

Section: Discussionmentioning

confidence: 99%

NF-κB-mediated IAP expression induces resistance of intestinal epithelial cells to apoptosis after polyamine depletion

Zou¹,

Rao²,

Guo³

et al. 2004

American Journal of Physiology-Cell Physiology

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Apoptosis plays a crucial role in maintenance of intestinal epithelial integrity and is highly regulated by numerous factors, including cellular polyamines. We recently showed that polyamines regulate nuclear factor (NF)-kappaB activity in normal intestinal epithelial (IEC-6) cells and that polyamine depletion activates NF-kappaB and promotes resistance to apoptosis. The current study went further to determine whether the inhibitors of apoptosis (IAP) family of proteins, c-IAP2 and XIAP, are downstream targets of activated NF-kappaB and play a role in antiapoptotic activity of polyamine depletion in IEC-6 cells. Depletion of cellular polyamines by alpha-difluoromethylornithine not only activated NF-kappaB activity but also increased expression of c-IAP2 and XIAP. Specific inhibition of NF-kappaB by the recombinant adenoviral vector containing IkappaBalpha superrepressor (AdIkappaBSR) prevented the induction of c-IAP2 and XIAP in polyamine-deficient cells. Decreased levels of c-IAP2 and XIAP proteins by inactivation of NF-kappaB through AdIkappaBSR infection or treatment with the specific inhibitor Smac also overcame the resistance of polyamine-depleted cells to apoptosis induced by the combination of tumor necrosis factor (TNF)-alpha and cycloheximide (CHX). Although polyamine depletion did not alter levels of procaspase-3 protein, it inhibited formation of the active caspase-3. Decreased levels of c-IAP2 and XIAP by Smac prevented the inhibitory effect of polyamine depletion on the cleavage of procaspase-3 to the active caspase-3. These results indicate that polyamine depletion increases expression of c-IAP2 and XIAP by activating NF-kappaB in intestinal epithelial cells. Increased c-IAP2 and XIAP after polyamine depletion induce the resistance to TNF-alpha/CHX-induced apoptosis, at least partially, through inhibition of the caspase-3 activity.

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Section: Discussionmentioning

confidence: 99%

NF-κB-mediated IAP expression induces resistance of intestinal epithelial cells to apoptosis after polyamine depletion

Zou¹,

Rao²,

Guo³

et al. 2004

American Journal of Physiology-Cell Physiology

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“…Apart from activation of PKC and PI3-kinase, PMA is also an activator of PKA (70). The cAMP/PKA pathway is an alternative pathway of transcriptional regulation of IAP-1 expression and may constitute a powerful protective agent in cells exposed to stress conditions (71). Treatment with the selective PKA inhibitor, H89, did not attenuate the PMA-induced cIAP-2 expression, suggesting that PKA is not FIG.…”

Section: Ciap-2 Regulation In Human Colon Cancersmentioning

confidence: 98%

Induction of cIAP-2 in Human Colon Cancer Cells through PKCδ/NF-κB

Wang

Evers

2003

Journal of Biological Chemistry

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Activation of protein kinase C (PKC) prevents apoptosis in certain cells; however, the mechanisms are largely unknown. Inhibitors of apoptosis (IAP) family members, including NAIP, cIAP-1, cIAP-2, XIAP/hILP, survivin, and BRUCE, block apoptosis by binding and potently inhibiting caspases. Activation of NF-B contributes to cIAP-2 induction; however, the cellular mechanisms regulating cIAP-2 expression have not been entirely defined. In this study, we examined the role of the PKC and NF-B pathways in the regulation of cIAP-2 in human colon cancers. We found that cIAP-2 mRNA levels were markedly increased in human colon cancer cells by treatment with the phorbol ester, phorbol-12-myristate-13-acetate (PMA), or bryostatin 1. Inhibitors of the Ca 2؉ -independent, novel PKC isoforms, but not inhibitors of MAPK, PI3-kinase, or PKA, blocked PMA-stimulated cIAP-2 mRNA expression, suggesting a role of PKC in PMA-mediated cIAP-2 induction. Pretreatment with the PKC␦-selective inhibitor rottlerin or transfection with an antisense PKC␦ oligonucleotide inhibited PMA-induced cIAP-2 expression, whereas cotransfection with a PKC␦ plasmid induced cIAP-2 promoter activity, which, taken together, identifies a role for PKC␦ in cIAP-2 induction. Treatment with the proteasome inhibitor, MG132 or inhibitors of NF-B (e.g. PDTC and gliotoxin), decreased PMA-induced up-regulation of cIAP-2. PMAinduced NF-B activation was blocked by either GF109203x, MG132, PDTC, or gliotoxin. Moreover, overexpression of PKC␦-induced cIAP-2 promoter activity and increased NF-B transactivation, suggesting regulation of cIAP-2 expression by a PKC␦/NF-B pathway. In conclusion, our findings demonstrate a role for a PKC/NF-B-dependent pathway in the regulation of cIAP-2 expression in human colon cancer cells. These data suggest a novel mechanism for the anti-apoptotic function mediated by the PKC␦/NF-B/cIAP-2 pathway in certain cancers.

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“…cAMP regulates numerous cellular processes, including gene expression, cell differentiation, cell cycle progression and apoptosis, both in a PKA-dependent and PKA-independent manner [17-19]. Some studies indicate that analogues of cyclic nucleotides cause apoptosis in renal mesangial cells, multiple myeloma cells and human cancer cell-sandactivation of cAMP signaling enhances Fas-mediated apoptosis and activation-induced cell death through potentiation of caspase-8 activation [20-23]. In contrast, there have also been studies that have shown that cAMP analogues inhibit apoptosis induced by different stimuli in hepatocytes, neutrophils, smooth muscle cells, andpre-B acute lymphoblastic leukemia NALM-6 cells [15,24,25].…”

Section: Introductionmentioning

confidence: 99%

cAMP prevents TNF-induced apoptosis through inhibiting DISC complex formation in rat hepatocytes

Bhattacharjee

Xiang

Wang

et al. 2012

Biochemical and Biophysical Research Communications

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Tumor necrosis factor α (TNF) is a pleiotropic proinflammatory cytokine that plays a role in immunity and the control of cell proliferation, cell differentiation, and apoptosis. The pleiotropic nature of TNF is due to the formation of different signaling complexes upon the binding of TNF to its receptor, TNF receptor type 1 (TNFR1). TNF induces apoptosis in various mammalian cells when the cells are co-treated with a transcription inhibitor like actinomycin D (ActD). When TNFR1 is activated, it recruits an adaptor protein, TNF receptor-associated protein with death domain (TRADD), through its cytoplasmic death effector domain (DED). TRADD, in turn, recruits other signaling proteins, including TNF receptor-associated protein 2 (TRAF2) and receptor-associated protein kinase (RIPK) 1, to form a complex. Subsequently, this complex combines with FADD and procaspase-8, converts into a death-inducing signaling complex (DISC) to induce apoptosis. Cyclic AMP (cAMP) is a second messenger that regulates various cellular processes such as cell proliferation, gene expression, and apoptosis. cAMP analogues are reported to act as anti-apoptotic agents in various cell types, including hepatocytes. We found that a cAMP analogue, dibutyryl cAMP (db-cAMP), inhibits TNF + ActD-induced apoptosis in rat hepatocytes. The protein kinase A (PKA) inhibitor KT-5720 reverses this inhibitory effect of cAMP on apoptosis. Cytoprotection by cAMP involves down-regulation of various apoptotic signal regulators like TRADD and FADD and inhibition of caspase-8 and caspase-3 cleavage. We also found that cAMP exerts its affect at the proximal level of TNF signaling by inhibiting the formation of the DISC complex upon the binding of TNF to TNFR1. In conclusion, our study shows that cAMP prevents TNF + ActD-induced apoptosis in rat hepatocytes by inhibiting DISC complex formation.

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Cyclic AMP increases rat inhibitor of apoptosis protein (RIAP1) mRNA in renal mesangial cells

Abstract: These data establish, to our knowledge for the first time, that RIAP1 mRNA levels are regulated by the cAMP-signaling pathway and suggest potential new avenues of therapy to modulate apoptosis.

Cited by 7 publications

References 35 publications

NF-κB-mediated IAP expression induces resistance of intestinal epithelial cells to apoptosis after polyamine depletion

NF-κB-mediated IAP expression induces resistance of intestinal epithelial cells to apoptosis after polyamine depletion

Induction of cIAP-2 in Human Colon Cancer Cells through PKCδ/NF-κB

cAMP prevents TNF-induced apoptosis through inhibiting DISC complex formation in rat hepatocytes

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