Distinct Role of cAMP and cGMP in the Cell Cycle Control of Vascular Smooth Muscle Cells

Fukumoto, Shinya; Koyama, Hideki; Hosoi, Masayuki; Yamakawa, Kenjiro; Tanaka, Shinji; Morii, Hirotoshi; Nishizawà, Yoshiki

doi:10.1161/01.res.85.11.985

Cited by 90 publications

(55 citation statements)

References 49 publications

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“…Thus, in human vascular smooth muscle cells, cGMP delays the G 1 ͞S transition by down-regulation of cyclin D1 and cyclin-dependent kinase 4 activities after platelet-derived growth factor stimulation (25). Also, cGMP suppresses human T cell proliferation by inhibiting IL-2 release (26).…”

Section: Resultsmentioning

confidence: 99%

Bacterial enterotoxins are associated with resistance to colon cancer

Pitari

Zingman

Hodgson

et al. 2003

Proc. Natl. Acad. Sci. U.S.A.

138

220

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One half million patients suffer from colorectal cancer in industrialized nations, yet this disease exhibits a low incidence in underdeveloped countries. This geographic imbalance suggests an environmental contribution to the resistance of endemic populations to intestinal neoplasia. A common epidemiological characteristic of these colon cancer-spared regions is the prevalence of enterotoxigenic bacteria associated with diarrheal disease. Here, a bacterial heat-stable enterotoxin was demonstrated to suppress colon cancer cell proliferation by a guanylyl cyclase C-mediated signaling cascade. The heat-stable enterotoxin suppressed proliferation by increasing intracellular cGMP, an effect mimicked by the cellpermeant analog 8-br-cGMP. The antiproliferative effects of the enterotoxin and 8-br-cGMP were reversed by L-cis-diltiazem, a cyclic nucleotide-gated channel inhibitor, as well as by removal of extracellular Ca 2؉ , or chelation of intracellular Ca 2؉ . In fact, both the enterotoxin and 8-br-cGMP induced an L-cis-diltiazem-sensitive conductance, promoting Ca 2؉ influx and inhibition of DNA synthesis in colon cancer cells. Induction of this previously unrecognized antiproliferative signaling pathway by bacterial enterotoxin could contribute to the resistance of endemic populations to intestinal neoplasia, and offers a paradigm for targeted prevention and therapy of primary and metastatic colorectal cancer.

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Section: Resultsmentioning

confidence: 99%

Bacterial enterotoxins are associated with resistance to colon cancer

Pitari

Zingman

Hodgson

et al. 2003

Proc. Natl. Acad. Sci. U.S.A.

138

220

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“…These data suggest that developmental retardation of zebrafish embryos caused by dominant negative ABCC5 is closely associated with cell cycle arrest but not apoptosis. Additionally, cGMP has been reported to be able to promote cell cycle arrest through modulating the machinery directly involved in the control of cell cycle progression (Fukumoto et al, 1999;Villalobo, 2006) and the increase of intracellular cGMP level induces cell cycle arrest and apoptosis in a broad spectrum of tumor cells (Savai et al, 2010). Furthermore, cGMP exposure is able to induce expression of p21 in adventitial fibroblasts .…”

Section: Discussionmentioning

confidence: 99%

Molecular analysis, developmental function and heavy metal-induced expression of ABCC5 in zebrafish

Long

et al. 2011

Comparative Biochemistry and Physiology Part B: Biochemistry an

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“…Both cGMP and over expression of its downstream kinase, cGMP-dependent protein kinase (PKG), have been shown to decrease cyclins D1, A, and E expression in vascular smooth muscle cells. [68][69][70] CNP also blocks NGF-induced increases in p27 and increases in cdk4 in response to BDNF.…”

confidence: 90%

Progressive and Inhibitory Cell Cycle Proteins Act Simultaneously to Regulate Neurotrophin-mediated Proliferation and Maturation of Neuronal Precursors

Simpson

Moon²,

Kleman

et al. 2007

Cell Cycle

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ACKnowlEdGEMEntSWe thank Amy Palmer for helpful discussions and reading of the manuscript, and Susan McTeer for manuscript preparation. This work was supported by grants NIDCD RO3 DC005704 to P.J.S., NIDCD RO1 DC02979 and NINDS RO1 NS39657 to G.V.R. AbStRACtNeuronal stem cell expansion and differentiation is a process involving stages of proliferation and maturation governed by the sequential and combinatorial exposure of cells to extrinsic factors. The olfactory epithelium is an excellent model to investigate regulation of this process, as it undergoes neuronal replacement post-natally. We have shown that the neurotrophins NGF and BDNF sequentially promote proliferation of developing olfactory sensory neuronal precursors, although their kinetics of proliferation and cell fate outcomes differ. Interestingly, CNP inhibits this neurotrophin-induced proliferation and promotes the maturation of these precursors to their next developmental stage. Here, we investigate the mechanisms behind these actions. Both NGF and BDNF increase the expression of cyclin D1 and cyclin-dependent kinase 4 (cdk4), with temporal expression patterns that parallel the proliferation kinetics of their cellular targets. The timing of cyclin D1 expression reflects differences in the need for transcription and translation in early and late stage precursors. CNP inhibits neurotrophin-induced cyclin D1 expression, and induces the expression of different profiles of inhibitory cell cycle proteins, which are neurotrophin-specific and correlate with the attainment of different maturational cell fates. Inhibition of protein degradation reverses the effects of neurotrophins and CNP on cyclin D1 and inhibitor expression levels, respectively. These results suggest a model for cell cycle regulation that involves the simultaneous expression of progressive and inhibitory cell cycle regulatory proteins in response to both proliferation and differentiation agents, followed by selective degradation of these proteins, providing a mechanism for rapid and exquisite control of the cell cycle.

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Distinct Role of cAMP and cGMP in the Cell Cycle Control of Vascular Smooth Muscle Cells

Cited by 90 publications

References 49 publications

Bacterial enterotoxins are associated with resistance to colon cancer

Bacterial enterotoxins are associated with resistance to colon cancer

Molecular analysis, developmental function and heavy metal-induced expression of ABCC5 in zebrafish

Progressive and Inhibitory Cell Cycle Proteins Act Simultaneously to Regulate Neurotrophin-mediated Proliferation and Maturation of Neuronal Precursors

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