Original Research: Local TAT-p27<sup>Kip1</sup> Fusion protein inhibits cell proliferation in rat Carotid                 arteries

Neukamm, Birgit; Miyakawa, Ayumi Aurea; Fukada, Sandra Yasuyo; Andrade, Cláudia Regina de; Pacheco, Fernando P; Silva, Thaís G. da; Ramalho, Leandra Náira Zambelli; Oliveira, Ana Maria de

doi:10.1177/1753944708090170

Cited by 4 publications

(5 citation statements)

References 24 publications

(32 reference statements)

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“…Extracellular p27 decreased proliferation of examined cell lines, depending on the type of cells and form of p27 protein. Similar results were observed earlier on variety of tumor cell lines [31] as well as on rabbit endothelial cells [32].…”

Section: Discussionsupporting

confidence: 90%

TAT-Mediated Delivery of p27 in Tumor Cell Lines as a Potential Therapeutic Peptide

Grdisa

2012

jcru

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TAT-fusion proteins (TAT-wt-p27, TAT-pt-p27, TAT-N'-p27) were introduced into the cells by protein transduction method. The mechanism by which transduced 27 influences on the regulation of cell cycle and apoptosis, were explored. TAT-p27-fusion proteins affected the proliferation of examined cell lines depending on type of the cells and protein. Transduced p27 induced accumulation of cyclin D1 and D3, with slight differences among the form of protein. Expression of cyclin D2 and E was mainly unchanged. Furthermore, TAT fusion proteins promoted apoptosis, which resulted in activation of caspase 3, appearance of poly (ADP-ribose) polymerase and DNA fragments, as well as the activation of apoptosis-inducing factor. The results pointed that transduced p27 activates apoptosis through activation of different signal transduction pathways. Thus, the molecule of p27 could be appropriate for treatment of tumors with deregulated its function. Also, the protein transduction method could find the application in specifically targeted cancer therapy.

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Section: Discussionsupporting

confidence: 90%

TAT-Mediated Delivery of p27 in Tumor Cell Lines as a Potential Therapeutic Peptide

Grdisa

2012

jcru

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“…Although a complete molecular mechanism for this wide range of defects is currently unknown, our findings suggest a defect in the p27 Kip1 pathway, and the remodeling of the primitive coronary plexus, possibly related to compact myocardial thinning. Finally, the findings reported here represent the basis for new insight into the development of cardiac malformations in general.p27 Kip1 is up‐regulated in 14‐3‐3ε −/− (Kosaka et al, ) and can play a crucial role at several levels because of its ubiquitous expression (Neukamm et al, ; Sakai et al, ; Merchant et al, ). In this study, we identified abnormal patterning of p27 Kip1 in the myocardial wall as well as the endocardial and possibly the epicardial populations.…”

Section: Discussionmentioning

confidence: 73%

“…The latter has been described in the Ptx1 mutant mouse (Bergwerff et al, 1998), which, however, cannot yet be conclusively linked to the findings in 14-3-3e À/À hearts or p27 Kip1 expression. Nevertheless, all differentiated cellular contributions to the arterial pole vasculature express 14-3-3e (McConnell et al, 1995) and p27 Kip1 (Neukamm et al, 2008;Sakai et al, 2010). Remodeling of the aortic (pharyngeal) arch arteries is known to be related to NCC and the second heart field (Bartram et al, 2001;Molin et al, 2002;Molin et al, 2003;Poelmann et al, 2004;Ward et al, 2005;High and Epstein, 2008;Keyte and Hutson, 2012), as well as Notch (High and Epstein, 2008) and TGFb signaling (Bartram et al, 2001;Molin et al, 2002;Molin et al, 2003).…”

Section: Developmental Dynamicsmentioning

confidence: 99%

“…Since p57 kip2 has a limited spatiotemporal expression in cardiac development (Burton et al, 1999;Kochilas et al, 1999) and p15 Ink4b can regulate p27 Kip1 (Reynisdottir and Massague, 1997), p27 Kip1 has been proposed as the key mediator of G 1 arrest in 14-3-3e À/À mice (Kosaka et al, 2012). Moreover, p27 Kip1 is found in many tissues, including VSMCs (Neukamm et al, 2008) and endothelial cells (Sakai et al, 2010); and both cardiospecific overexpression (Lavine et al, 2008) and germ line deletion of p27 Kip1 (Merchant et al, 2016) lead to ventricular non-compaction in mice. Although the study by Kosaka et al has identified ventricular septal defects (VSDs) in 14-3-3e À/À mice (Kosaka et al, 2012), this work primarily focused on the non-compaction phenotype.…”

Section: Introductionmentioning

confidence: 99%

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14‐3‐3epsilon controls multiple developmental processes in the mouse heart

Groot

Hoppenbrouwers

Miquerol

et al. 2016

Developmental Dynamics

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Background 14-3-3ε plays an important role in the maturation of the compact ventricular myocardium by modulating the cardiomyocyte cell cycle via p27kip1. However, additional cardiac defects are possible given the ubiquitous expression pattern of this protein. Results Germline deletion of 14-3-3ε led to malalignment of both the outflow tract (OFT) and atrioventricular (AV) cushions, with resulting tricuspid stenosis and atresia, mitral valve abnormalities, and perimembranous ventricular septal defects (VSDs). We confirmed myocardial non-compaction, and detected a spongy septum with muscular VSDs and blebbing of the epicardium. These defects were associated with abnormal patterning of p27kip1 expression in the subendocardial and possibly the epicardial cell populations. In addition to abnormal pharyngeal arch artery patterning, we found deep endocardial recesses and paucity of intramyocardial coronary vasculature as a result of defective coronary plexus remodeling. Conclusions The malalignment of both endocardial cushions provides a new explanation for tricuspid and mitral valve defects, while myocardial non-compaction provides the basis for the abnormal coronary vasculature patterning. These abnormalities might arise from p27kip1 dysregulation and a resulting defect in epithelial to mesenchymal transformation. These data suggest that 14-3-3ε, in addition to left ventricular non-compaction (LVNC), might be linked to different forms of congenital heart disease (CHD).

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“…Vasssalo et al. unpublished data) and during adventitia remodelling in rat carotid artery injury (Neukamm et al. 2008).…”

Section: Discussionmentioning

confidence: 99%

Apoptosis, cell proliferation and modulation of cyclin‐dependent kinase inhibitor p21^cip1 in vascular remodelling during vein arterialization in the rat

Borin

Miyakawa

Cardoso

et al. 2009

Int J Experimental Path

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Neo-intima development and atherosclerosis limit long-term vein graft use for revascularization of ischaemic tissues. Using a rat model, which is technically less challenging than smaller rodents, we provide evidence that the temporal morphological, cellular, and key molecular events during vein arterialization resemble the human vein graft adaptation. Right jugular vein was surgically connected to carotid artery and observed up to 90 days. Morphometry demonstrated gradual thickening of the medial layer and important formation of neo-intima with deposition of smooth muscle cells (SMC) in the subendothelial layer from day 7 onwards. Transmission electron microscopy showed that SMCs switch from the contractile to synthetic phenotype on day 3 and new elastic lamellae formation occurs from day 7 onwards. Apoptosis markedly increased on day 1, while alpha-actin immunostaining for SMC almost disappeared by day 3. On day 7, cell proliferation reached the highest level and cellular density gradually increased until day 90. The relative magnitude of cellular changes was higher in the intima vs. the media layer (100 vs. 2 times respectively). Cyclin-dependent kinase inhibitors (CDKIs) p27(Kip1) and p16(INKA) remained unchanged, whereas p21(Cip1) was gradually downregulated, reaching the lowest levels by day 7 until day 90. Taken together, these data indicate for the first time that p21(Cip1) is the main CDKI protein modulated during the arterialization process the rat model of vein arterialization that may be useful to identify and validate new targets and interventions to improve the long-term patency of vein grafts.

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Original Research: Local TAT-p27^Kip1 Fusion protein inhibits cell proliferation in rat Carotid arteries

Abstract: Taken together, these results provide evidence that TAT-p27(Kip1) can inhibit vascular cells proliferation. It is the first successful demonstration that the cell permeable TAT-p27(Kip1) has potential as a vascular anti-proliferative agent.

Cited by 4 publications

References 24 publications

TAT-Mediated Delivery of p27 in Tumor Cell Lines as a Potential Therapeutic Peptide

TAT-Mediated Delivery of p27 in Tumor Cell Lines as a Potential Therapeutic Peptide

14‐3‐3epsilon controls multiple developmental processes in the mouse heart

Apoptosis, cell proliferation and modulation of cyclin‐dependent kinase inhibitor p21^cip1 in vascular remodelling during vein arterialization in the rat

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Original Research: Local TAT-p27Kip1 Fusion protein inhibits cell proliferation in rat Carotid arteries

Abstract: Taken together, these results provide evidence that TAT-p27(Kip1) can inhibit vascular cells proliferation. It is the first successful demonstration that the cell permeable TAT-p27(Kip1) has potential as a vascular anti-proliferative agent.

Cited by 4 publications

References 24 publications

TAT-Mediated Delivery of p27 in Tumor Cell Lines as a Potential Therapeutic Peptide

TAT-Mediated Delivery of p27 in Tumor Cell Lines as a Potential Therapeutic Peptide

14‐3‐3epsilon controls multiple developmental processes in the mouse heart

Apoptosis, cell proliferation and modulation of cyclin‐dependent kinase inhibitor p21cip1 in vascular remodelling during vein arterialization in the rat

Contact Info

Product

Resources

About

Original Research: Local TAT-p27^Kip1 Fusion protein inhibits cell proliferation in rat Carotid arteries

Apoptosis, cell proliferation and modulation of cyclin‐dependent kinase inhibitor p21^cip1 in vascular remodelling during vein arterialization in the rat