Cell Cycle Regulatory Proteins in the Liver in Murine <i>Trypanosoma cruzi</i> Infection

Bouzahzah, Boumediene; Nagajyothi, Fnu; Desruisseaux, Mahalia S.; Krishnamachary, Mohan; Factor, Stephen M.; Cohen, Arnold W.; Lisanti, Michael P.; Petkova, Stefka B.; Pestell, Richard G.; Wittner, Murray; Mukherjee, Shankar; Weiss, Louis M.; Jelicks, Linda A.; Albanese, Chris; Tanowitz, Herbert B.

doi:10.4161/cc.5.20.3380

Cited by 14 publications

(15 citation statements)

References 27 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…[2][3][4][5] In the present study we reaffirmed in cultured L 6 E 9 myoblasts that infection indeed increased the levels of cyclin D1. In order to examine the mechanism by which the parasite causes increased cyclin D1 levels, we used two cyclin D1 reporters which were transfected into myoblasts, either the luciferase reporter construct of the full length (1745) cyclin D1 gene promoter or a cyclin D1 luciferase reporter construct mutated at the AP-1 and ATF binding sites.…”

Section: Discussionsupporting

confidence: 82%

“…4 For example, in our in vivo experiments, we discovered that the hearts quickly displayed an increase in the expression of cyclin D1 as well as other cyclins, such as cyclin E and cyclin A. 2 The induction of cyclin A and cyclin E indicate that a reversion to a fetal or neonatal phenotype may be occurring within the infected heart. The ERK signaling pathway regulates the expression of cyclin D1 and both are negatively regulated by caveolin-1.…”

Section: Discussionmentioning

confidence: 93%

“…19 We have also demonstrated previously that infection caused a reduction in the expression of caveolin-1 both in vitro and in vivo. 2,3,5 Despite these findings, the mechanism(s) by which host cyclin D1 abundance was regulated by T. cruzi in the myocardium had not been previously investigated. We anticipated that infection of myoblasts would result in an increase in transcription of cyclin D1, resulting in increased cyclin D1 protein levels.…”

Section: Discussionmentioning

confidence: 99%

“…The consequences of T. cruzi infection on host cell cycle regulatory proteins have been extensively investigated both in cultured cells and mouse models. [2][3][4][5][6] Previously we demonstrated that T. cruzi infection of CD1 mice resulted in increased cyclin D1 expression, increased ERK activation and increased AP-1 and NFκB DNA binding activity. 4 As we have previously shown, cyclin D1 gene expression is regulated in part by transcriptional activation, which can be mediated by the MAPK pathway and NFκB.…”

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Regulation of host cell cyclin D1 byTrypanosoma cruziin myoblasts

Bouzahzah¹,

Yurchenko²,

Nagajyothi³

et al. 2008

Cell Cycle

Self Cite

View full text Add to dashboard Cite

Infection with the parasite Trypanosoma cruzi causes Chagas disease. In this study we demonstrated that there was an increase in cyclin D1 expression in T. cruzi (Tulahuen strain)-infected myoblasts. To examine a possible mechanism for the increased cyclin D1 expression we transfected L 6 E 9 myoblasts with cyclin D1 luciferase reporter constructs and infected with T. cruzi. There was no evidence of an increase in promoter activity. Additionally, quantitative PCR did not demonstrate any change in cyclin D1 message during infection. Moreover, we demonstrated that the cyclin D1 protein was significantly stabilized after infection. Collectively, these data indicate that infection with T. cruzi increases cyclin D1 protein abundance post-translationally.

show abstract

Section: Discussionsupporting

confidence: 82%

Section: Discussionmentioning

confidence: 93%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Regulation of host cell cyclin D1 byTrypanosoma cruziin myoblasts

Bouzahzah¹,

Yurchenko²,

Nagajyothi³

et al. 2008

Cell Cycle

Self Cite

View full text Add to dashboard Cite

show abstract

“…In addition, T. cruzi also infects the reticuloendothelial system including the liver, spleen, and bone marrow. [18][19][20][21]. The existence of an immunosuppressive activity exerted by MDSCs during acute T. cruzi infection has been previously reported [22].…”

Section: Introductionmentioning

confidence: 99%

Myeloid‐derived suppressor cells are key players in the resolution of inflammation during a model of acute infection

et al. 2013

View full text Add to dashboard Cite

Myeloid-derived suppressor cells (MDSCs Keywords: Inflammation r MDSCs r Nitric oxide r ROS r Trypanosoma cruziAdditional supporting information may be found in the online version of this article at the publisher's web-site IntroductionMyeloid-derived suppressor cells (MDSCs) are a heterogeneous cell population consisting of immature macrophages, granulocytes, and dendritic cells as well as myeloid progenitor cells. They are considered to be one of the major components of the immune suppressive network responsible for suppressing T-cell responses in pathological conditions [1,2] as well as in the regulation of the immune response in healthy individuals [3]. These Correspondence: Dr. Susana Gea e-mail: sgea@fcq.unc.edu.ar myeloid cells are commonly identified in mice by the co-expression of the surface markers CD11b and Gr1 (Ly6G/Ly6C) and have been divided into two subsets: granulocytic (G) MDSCs with a CD11b + LY6G + LY6C low phenotype and monocytic (M) MDSCs with CD11b + LY6G − LY6C high phenotype [3,4]. Despite their morphological similarities, G-MDSCs and neutrophils are functionally and phenotypically different. G-MDSCs, but not neutrophils, are immunosuppressive and express higher levels of arginase-1 and myeloperoxidase than neutrophils, and also have increased production of reactive oxygen species (ROS) [5,6]. Although * These authors contributed equally to this work.www.eji-journal.eu Eur. J. Immunol. 2014. 44: 184-194 Immunomodulation 185 M-MDSCs and inflammatory monocytes share the same phenotype and morphology, these cells are functionally distinct since M-MDSCs are highly immunosuppressive and they express high levels of both iNOS and arginase-1. Furthermore, although iNOS expression is a hallmark of a tumoricidal/microbicidal phenotype in M1 macrophages, iNOS promotes suppressive activities in M-MDSCs. This shift in iNOS activity most likely reflects the crosstalk of iNOS with other enzymes such as NADPH oxidase to promote the production of peroxynitrites, which inhibits the proliferation and effector function of T cells [2]. MDSCs use several mechanisms in addition to the production of ROS and NO, such as triggering apoptosis of activated T cells by depleting of L-arginine, via arginase [7][8][9][10]. There is also evidence that MDSCs may suppress immune activation by inducing T regulatory cell expansion [11]. Other suppressive mechanisms that have recently been proposed include the production of TGF-β [12,13], depletion of cysteine [8], induction of COX2 and prostaglandin E2 [1,[14][15][16].Trypanosoma cruzi an obligate intracellular protozoan, is the causative agent of Chagas disease. This disease affects about 20 million people in Latin America, with 120 million persons at risk. In the past decades, mainly as a result of increased migrations, the diagnosed cases have also increased in nonendemic countries such as Canada, United States of America, and Europe. This has led to an increased risk of transmission of the infection, mainly through blood transfusion and organ transplantation [17]. Pa...

show abstract