Effect of cyclic AMP and prostaglandin E2 on the induction of nitric oxide- and prostanoid-forming pathways in cultured rat mesangial cells

Nüsing, Rolf M.; Klein, Thomas; Pfeilschifter, Josef; Ullrich, Volker

doi:10.1042/bj3130617

Cited by 55 publications

(21 citation statements)

References 34 publications

(34 reference statements)

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“…Similar effects have also been seen in renal mesangial cells (13,18) and brown adipocytes (19). Although cAMP alone does not induce iNOS in unstimulated cardiac myocytes, it augments iNOS induction in interleukin-1␤-stimulated cells (20).…”

Section: Discussionsupporting

confidence: 51%

“…An increase in intracellular cAMP levels is an important intracellular signaling mechanism involved in the regulation of gene expression. Certain in vitro studies have shown that an increase in cAMP levels causes iNOS induction (12)(13)(14), whereas in other studies, increased cAMP levels caused a reduction in iNOS (15,16). In the present study, we explored the intracellular signaling pathway for the LPS-induced increase in cAMP levels and its involvement in LPSstimulated NO production in RAW 264.7 macrophages.…”

mentioning

confidence: 97%

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Role of the Cyclic AMP-Protein Kinase A Pathway in Lipopolysaccharide-induced Nitric Oxide Synthase Expression in RAW 264.7 Macrophages

Chen

Chiu

Sun

et al. 1999

Journal of Biological Chemistry

102

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Section: Discussionsupporting

confidence: 51%

mentioning

confidence: 97%

Role of the Cyclic AMP-Protein Kinase A Pathway in Lipopolysaccharide-induced Nitric Oxide Synthase Expression in RAW 264.7 Macrophages

Chen

Chiu

Sun

et al. 1999

Journal of Biological Chemistry

102

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“…Different studies reported that the increase of intracellular cAMP level enhanced PGHS-2 expression in various cell types (17)(18)(19)(20). In agreement with these findings, we established that forskolin, which enhances intracellular cAMP level by stimulating adenylyl cyclase, significantly increases PGHS-2 expres- sion in HPMECs.…”

Section: Discussionsupporting

confidence: 80%

“…Finally, the increase of intracellular cAMP rate enhances PGHS-2 expression in various cell types (17)(18)(19)(20).…”

mentioning

confidence: 99%

Inhibition by Extracellular cAMP of Phorbol 12-Myristate 13-Acetate-induced Prostaglandin H Synthase-2 Expression in Human Pulmonary Microvascular Endothelial Cells

Elalamy¹,

Said²,

Singer³

et al. 2000

Journal of Biological Chemistry

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Exposure of human pulmonary microvascular endothelial cells (HPMECs) to phorbol 12-myristate 13-acetate (PMA) leads to the increase of prostaglandin H synthase (PGHS)-2 protein levels. Under same conditions and according to its constitutive nature, no significant variation of PGHS-1 protein was noted. The elevation of the intracellular cAMP rate is known to enhance PGHS-2 levels through a protein kinase A pathway in various cells. To determine whether the extracellular cAMP also regulates the inducible expression of PGHS, cultured HPMECs were exposed to cAMP alone or in combination with PMA. The PMA-induced PGHS-2 protein was attenuated by the extracellular cAMP. In addition, PGHS-2 activity evaluated through 6-keto-PGF1␣ generation, which was enhanced by PMA was inhibited by extracellular cAMP. Furthermore, in HPMEC medium, PMA-induced PGHS-2 expression was accompanied by the generation of a transferable activity (TA) able to abolish platelet aggregation. This resulting TA was dependent from PGHS-2 pathway, because NS-398, a selective inhibitor of PGHS-2, suppressed its production. The inhibitory TA released by treated HPMECs was also prevented by extracellular cAMP. The specific protein kinase A (PKA) inhibitor blocked the extracellular cAMP effect on both PMA-induced 6-keto-PGF1␣ synthesis and inhibitory TA generation, suggesting the involvement of PKA signaling at the outer surface of HPMECs. Accordingly, we established, in phosphorylation experiments, the presence of an endothelial ectoprotein kinase activity, able to phosphorylate the synthetic substrate kemptide in a cAMP-dependent mode. Reverse transcription-polymerase chain reaction analysis showed that PMA-induced PGHS-2 mRNA was markedly reduced by extracellular cAMP. Together, these findings provide the first experimental evidence that extracellular cAMP is able to reduce HPMEC PGHS-2 expression in terms of mRNA, protein, and enzyme activity through an ecto-PKA pathway. In addition, they outline the potential role of endothelial PGHS-2 in the limitation of platelet activation during inflammatory processes.

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“…In HaCaT cells, treatment with forskolin induces a transient phosphorylation of both CREB and ATF-1, and a 2 ± 3-fold induction of COX-2 promoter activity that is dependent on the COX-2 CRE. Interestingly, elevation of cellular level of cAMP also up-regulates the expression of endogenous COX-2 (Nusing et al, 1996;Oshima et al, 1991). Thus, a correlation exists between the phosphorylation of CREB or ATF-1 and the COX-2 promoter activity.…”

Section: Discussionmentioning

confidence: 99%

Role of cyclic AMP responsive element in the UVB induction of cyclooxygenase-2 transcription in human keratinocytes

et al. 2001

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It has been shown that UVB irradiation induces expression of COX-2 and up-regulation of COX-2 plays a functional role in UVB tumor promotion. In this study, we examined the cis-elements in the human COX-2 promoter that may be responsible for the UVB induction of COX-2. Analyses with the COX-2 promoter region revealed that the cyclic AMP responsive element near the TATA box was essential for both basal and UVB induced COX-2 expression. This was further supported by studies using a dominant negative mutant of CREB, which strongly inhibited the activity of COX-2 promoter. Electrophoretic mobility shift assays indicated that CREB and ATF-1 were the major proteins binding to the COX-2 CRE. CREB and ATF-1 were phosphorylated upon UVB treatment, and SB202190, a p38 MAPK inhibitor, decreased the phosphorylation of CREB/ATF-1 and suppressed COX-2 promoter activity. In contrast, treatment with forskolin, an activator of adenylyl cyclase, led to phosphorylation of CREB and ATF-1 and activation of COX-2 promoter. Finally, enhanced binding of phospho-CREB/ATF-1 to the COX-2 CRE was observed after UVB induction. Thus, one signaling pathway for UVB induction of human COX-2 involves activation of p38, subsequent phosphorylation of CREB/ATF-1, and activation of the COX-2 CRE through enhanced binding of phosphorylated CREB/ ATF-1. Oncogene (2001) 20, 5164 ± 5172.

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Effect of cyclic AMP and prostaglandin E2 on the induction of nitric oxide- and prostanoid-forming pathways in cultured rat mesangial cells

Cited by 55 publications

References 34 publications

Role of the Cyclic AMP-Protein Kinase A Pathway in Lipopolysaccharide-induced Nitric Oxide Synthase Expression in RAW 264.7 Macrophages

Role of the Cyclic AMP-Protein Kinase A Pathway in Lipopolysaccharide-induced Nitric Oxide Synthase Expression in RAW 264.7 Macrophages

Inhibition by Extracellular cAMP of Phorbol 12-Myristate 13-Acetate-induced Prostaglandin H Synthase-2 Expression in Human Pulmonary Microvascular Endothelial Cells

Role of cyclic AMP responsive element in the UVB induction of cyclooxygenase-2 transcription in human keratinocytes

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