The effect of hydrogen peroxide on the cyclin D expression in fiborblasts

Muñoz, Christian; Post, Jan Andries; Verkleij, Arie J.; Verrips, C. Theo; Boonstra, Johannes

doi:10.1007/pl00013204

Cited by 24 publications

(8 citation statements)

References 29 publications

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“…All these effects are also mediated by H 2 O 2 in different cell systems [32 -34]. In a previous study we found that 3,4-DHPEA increased the level of cyclin D in HL60 cells [10], an effect common to H 2 O 2 in fibroblasts [35].…”

Section: Discussionmentioning

confidence: 98%

Production of hydrogen peroxide is responsible for the induction of apoptosis by hydroxytyrosol on HL60 cells

Fabiani

Fuccelli

Pieravanti

et al. 2009

Molecular Nutrition Food Res

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Hydroxytyrosol [3,4-dihydroxyphenylethanol (3,4-DHPEA)], a phenolic compound found exclusively in olive oil, exerts growth-suppressive and pro-apoptotic effects on different cancer cells. Although some molecular mechanisms involved in the pro-apoptotic activity of 3,4-DHPEA have been proposed, the initial stress signals responsible of this phenomenon are not known. Our aim was to assess the involvement of reactive oxygen species as mediators of apoptosis induced by 3,4-DHPEA on HL60 cells. Apoptosis was determined by analyzing the nuclear fragmentation by both fluorescence microscopy and flow cytometry. The externalization of phosphatidylserine was evidenced using an Annexin V-FITC kit. The concentration of H(2)O(2) in the culture medium was measured by the ferrous ion oxidation-xylenol orange method. The pro-apoptotic effect of 3,4-DHPEA (100 muM) was prevented by N-acetyl-cysteine, ascorbate, and alpha-tocopherol. Catalase suppressed the 3,4-DHPEA-induced apoptosis, while the Fe(II)-chelating reagent o-phenantroline showed no effect, suggesting the involvement of H(2)O(2 )but not of OH(*). Indeed, 3,4-DHPEA caused accumulation of H(2)O(2) in the culture medium. Tyrosol (p-hydroxyphenylethanol) and caffeic acid, compounds structurally similar to 3,4-DHPEA but not able to generate H(2)O(2), did not induce an appreciable apoptotic effect. This is the first study demonstrating that apoptosis induction by 3,4-DHPEA is mediated by the extracellular production of H(2)O(2).

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Section: Discussionmentioning

confidence: 98%

Production of hydrogen peroxide is responsible for the induction of apoptosis by hydroxytyrosol on HL60 cells

Fabiani

Fuccelli

Pieravanti

et al. 2009

Molecular Nutrition Food Res

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“…As has been shown for cyclin D2, cyclin D1 is also known to increase cardiomyocyte cell cycling activity in vitro [43] , and transgenic mice models of cardiac-specific cyclin D1 or D2 overexpression clearly demonstrate that both induce increased cardiomyocyte cycling activity in vivo [23,33] . Cyclin D1 has also previously been suggested to be regulated by H 2 O 2 , via redox-dependent stabilisation of the cyclin D1 protein [44] . However, we found no evidence of increased cyclin D1 expression, at the level of either mRNA or protein, in the hearts of the 2 week old Nox4 Tg mice, suggesting that cyclin D1 is not the mediator of the increased cardiomyocyte proliferation in this mouse model (Supplementary data, Fig.…”

Section: Discussionmentioning

confidence: 99%

Redox regulation of cardiomyocyte cell cycling via an ERK1/2 and c-Myc-dependent activation of cyclin D2 transcription

Murray

Smyrnias

Schnelle

et al. 2015

Journal of Molecular and Cellular Cardiology

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Adult mammalian cardiomyocytes have a very limited capacity to proliferate, and consequently the loss of cells after cardiac stress promotes heart failure. Recent evidence suggests that administration of hydrogen peroxide (H2O2), can regulate redox-dependent signalling pathway(s) to promote cardiomyocyte proliferation in vitro, but the potential relevance of such a pathway in vivo has not been tested. We have generated a transgenic (Tg) mouse model in which the H2O2-generating enzyme, NADPH oxidase 4 (Nox4), is overexpressed within the postnatal cardiomyocytes, and observed that the hearts of 1–3 week old Tg mice pups are larger in comparison to wild type (Wt) littermate controls. We demonstrate that the cardiomyocytes of Tg mouse pups have increased cell cycling capacity in vivo as determined by incorporation of 5-bromo-2′-deoxyuridine. Further, microarray analyses of the transcriptome of these Tg mouse hearts suggested that the expression of cyclin D2 is significantly increased. We investigated the molecular mechanisms which underlie this more proliferative phenotype in isolated neonatal rat cardiomyocytes (NRCs) in vitro, and demonstrate that Nox4 overexpression mediates an H2O2-dependent activation of the ERK1/2 signalling pathway, which in turn phosphorylates and activates the transcription factor c-myc. This results in a significant increase in cyclin D2 expression, which we show to be mediated, at least in part, by cis-acting c-myc binding sites within the proximal cyclin D2 promoter. Overexpression of Nox4 in NRCs results in an increase in their proliferative capacity that is ablated by the silencing of cyclin D2. We further demonstrate activation of the ERK1/2 signalling pathway, increased phosphorylation of c-myc and significantly increased expression of cyclin D2 protein in the Nox4 Tg hearts. We suggest that this pathway acts to maintain the proliferative capacity of cardiomyocytes in Nox4 Tg pups in vivo and so delays their exit from the cell cycle after birth.

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“…The formation of the mixed disulfides is reversible and restoration of the GSSG:GSH ratio upon recovery from the oxidative stress will result in restoration of the free SH group of the cystein(s) involved. Accordingly, H 2 O 2 treatment resulted in a sustained expression of cyclins D1 and D2, caused by a transient inhibition of the ubiquitination process and/or the proteasome activity (Martínez Muñoz et al, 2001). Not only the ubiquitination process, but also the proteasome itself was inhibited by oxidative stress (Reinheckel et al, 1998;Szweda et al, 2002).…”

Section: Ros and Ubiquitin Pathwaymentioning

confidence: 95%

“…In these cells the cell cycle inhibition was accompanied by inhibition of cell spreading, focal adhesion formation and stress fiber formation during early G1 phase. Furthermore, H 2 O 2 caused a reversible inhibition of the ubiquitin-proteosome dependent degradation of cyclin D1 and D2 in HER14 fibroblasts (Martínez Muñoz et al, 2001). Exposure of the oligodendrocyte cell line CG4 to various amounts of H 2 O 2 resulted in stimulation of the PGDF receptor kinase and various MAP kinase pathways including ERK, p38 MAPK and c-Jun N-terminal kinase (JNK) and in cell death (Bhat and Zhang, 1999).…”

Section: Effect Of Ros On Regulators Of Cell Cycle Progressionmentioning

confidence: 99%

Molecular events associated with reactive oxygen species and cell cycle progression in mammalian cells

Boonstra

Post

2004

Gene

663

445

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Cell cycle progression is regulated by a wide variety of external factors, amongst them are growth factors and extracellular matrix factors. During the last decades evidence has been obtained that reactive oxygen species (ROS) may also play an important role in cell cycle progression. ROS may be generated by external and internal factors. In this overview we describe briefly the generation of ROS and their effects on processes that have been demonstrated to play an essential role in cell cycle progression, including such systems as signal transduction cascades, protein ubiquitination and degradation, and the cytoskeleton. These different effects of ROS influence cell cycle progression dependent upon the amount and duration of ROS exposure. Activation of growth factor stimulated signaling cascades by low levels of ROS result in increased cell cycle progression, or, in case of prolonged exposure, to a differentiation like growth arrest. From many studies it seems clear that the cyclin kinase inhibitor protein p21 plays a prominent role, leading to cell cycle arrest at higher but not directly lethal levels of ROS. Dependent upon the nature of p21 induction, the cell cycle arrest may be transient, coupled to repair processes, or permanent. At high concentrations of ROS all of the above processes are activated, in combination with enhanced damage to the building blocks of the cell, leading to apoptosis or even necrosis.

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The effect of hydrogen peroxide on the cyclin D expression in fiborblasts

Cited by 24 publications

References 29 publications

Production of hydrogen peroxide is responsible for the induction of apoptosis by hydroxytyrosol on HL60 cells

Production of hydrogen peroxide is responsible for the induction of apoptosis by hydroxytyrosol on HL60 cells

Redox regulation of cardiomyocyte cell cycling via an ERK1/2 and c-Myc-dependent activation of cyclin D2 transcription

Molecular events associated with reactive oxygen species and cell cycle progression in mammalian cells

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