Specific inhibition of eIF-5A and collagen hydroxylation by a single agent. Antiproliferative and fibrosuppressive effects on smooth muscle cells from human coronary arteries.

McCaffrey, Tim; Pomerantz, Kenneth B.; Sanborn, Timothy A.; Spokojny, Artur M.; Du, Baoheng; Park, M H; Folk, J.E.; Lamberg, Arja; Kivirikko, K.I.; Falcone, Domenick J.

doi:10.1172/jci117684

Cited by 54 publications

(39 citation statements)

References 46 publications

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“…It has been suggested previously that mimosine modulates the expression of specific genes at the translational level (6,8) through the inhibition of the formation of hypusinated eIF5A (53). The hypusine residue of eIF5A is critical to its function (24,54,55).…”

Section: Comparison Of the Effects Of Mimosine On Drg-1 Expression Wimentioning

confidence: 99%

Modulation of Differentiation-related Gene 1 Expression by Cell Cycle Blocker Mimosine, Revealed by Proteomic Analysis

Dong

Arnold

Yang

et al. 2005

Molecular & Cellular Proteomics

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L-Mimosine, a plant amino acid, can reversibly block mammalian cells at late G 1 phase and has been found to affect translation of mRNAs of the cyclin-dependent kinase inhibitor p27, eIF3a (eIF3 p170), and ribonucleotide reductase M2. The effect of mimosine on the expression of these genes may be essential for the G 1 phase arrest. To determine additional genes that may be early respondents to the mimosine treatment, we performed two-dimensional gel electrophoretic analysis of [35 S]methionine-labeled cell lysates followed by identification of the altered protein spots by LC-tandem mass spectrometry. In this study, the synthesis of two protein spots (MIP42 and MIP17) was found to be enhanced by mimosine, whereas the formation of another protein spot (MSP17) was severely blocked following mimosine treatment. These protein spots, MIP42, MIP17, and MSP17, were identified to be differentiation-related gene 1 (Drg-1; also called RTP, cap43, rit42, Ndrg-1, and PROXY-1), deoxyhypusine-containing eIF5A intermediate, and mature hypusine-containing eIF5A, respectively. The effect of mimosine on eIF5A maturation was due to inhibition of deoxyhypusine hydroxylase, the enzyme catalyzing the final step of hypusine biosynthesis in eIF5A. The mimosine-induced expression of Drg-1 was mainly attributable to increased transcription likely by the c-Jun/AP-1 transcription factor. Because induction of Drg-1 is an early event after mimosine treatment and is observed before a notable reduction in the steady-state level of mature eIF5A, eIF5A does not appear to be involved in the modulation of Drg-1 expression. Molecular & Cellular Proteomics 4:993-1001, 2005.

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Section: Comparison Of the Effects Of Mimosine On Drg-1 Expression Wimentioning

confidence: 99%

Modulation of Differentiation-related Gene 1 Expression by Cell Cycle Blocker Mimosine, Revealed by Proteomic Analysis

Dong

Arnold

Yang

et al. 2005

Molecular & Cellular Proteomics

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“…Previous studies have used cells grown from primary and restenotic vascular lesions to study their response to injuryinduced signals, such as TGF-␤ 1, as a model of the atherosclerotic/restenotic process (6,12). Although TGF-␤ 1 is a potent growth inhibitor for normal human SMC (13), cells derived from human atherosclerotic and restenotic lesions are resistant to the antiproliferative effect of TGF-␤ 1 (6).…”

Section: Introductionmentioning

confidence: 99%

Genomic instability in the type II TGF-beta1 receptor gene in atherosclerotic and restenotic vascular cells.

McCaffrey¹,

Du²,

Consigli³

et al. 1997

J. Clin. Invest.

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172

121

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Cells proliferating from human atherosclerotic lesions are resistant to the antiproliferative effect of TGF-␤ 1, a key factor in wound repair. DNA from human atherosclerotic and restenotic lesions was used to test the hypothesis that microsatellite instability leads to specific loss of the Type II receptor for TGF-␤ 1 (T ␤ R-II), causing acquired resistance to TGF-␤ 1. High fidelity PCR and restriction analysis was adapted to analyze deletions in an A 10 microsatellite within T ␤ R-II. DNA from lesions, and cells grown from lesions, showed acquired 1 and 2 bp deletions in T ␤ R-II, while microsatellites in the hMSH3 and hMSH6 genes, and hypermutable regions of p53 were unaffected. Sequencing confirmed that these deletions occurred principally in the replication error-prone A 10 microsatellite region, though nonmicrosatellite mutations were observed. The mutations could be identified within specific patches of the lesion, while the surrounding tissue, or unaffected arteries, exhibited the wild-type genotype. This microsatellite deletion causes frameshift loss of receptor function, and thus, resistance to the antiproliferative and apoptotic effects of TGF-␤ 1. We propose that microsatellite instability in T ␤ R-II disables growth inhibitory pathways, allowing monoclonal selection of a disease-prone cell type within some vascular lesions. ( J. Clin. Invest. 1997.

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“…This uncoupling of the effects of TGF-1 probably reflects quantitative changes in TGF-1 receptor signaling. The down-regulation of the T RII in smooth muscle cells derived from human atherosclerotic lesions is associated with loss of an antiproliferative response to TGF-1 but an overproduction of ECM components [51].…”

Section: Mock-so Mock-bdl End-so End-bdlmentioning

confidence: 99%

Endoglin Upregulation in the Liver after Bile Duct Ligation in Rats

Pérez‐Barriocanal¹

2011

TOGASJ

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Abstract:Background: Transforming growth factor beta 1 (TGF-1) has been implicated in the stimulation of extracellular matrix synthesis in acute and chronic liver disease. Endoglin (CD-105) is a membrane glycoprotein that binds TGF-1 with high affinity. Endoglin is overexpressed in several model of fibrosis. The goal of the present study was to evaluate the effect of bile duct ligation (BDL) on endoglin expression and the effect of endoglin overexpression on liver fibrosis in rats.Methods: Rat livers were transfected with a vector containing full length human endoglin (h-end) or an empty vector (mock) and 48 hours after were subjected to either BDL or sham operation (SO). Eighteen days after, a blood sample was obtained and bilirubin and serum enzyme activities were measured to assess liver damage. Liver fibrosis was quantified by a computer-assisted image analysis of Sirius red stained livers and by liver hydroxyproline content. Endoglin expression in the liver tissue was assessed by Western blot and immunohystochemistry.Results: Both immunohistochemistry and Western blot reveals endoglin upregulation after BDL in rats. In addition, these techniques also reveal effective human endoglin transfection in the rat's liver. After BDL, liver fibrosis and plasma levels of enzymes were similar in h-end transfected and mock-transfected rats. Western blots showed higher endoglin expression after BDL in h-end transfected and mock-transfected rats. Conclusions:The present study provides clear evidence that endoglin is upregulated in the liver of rats with BDL. h-end overexpression did not improve liver fibrosis after BDL in rats.

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Specific inhibition of eIF-5A and collagen hydroxylation by a single agent. Antiproliferative and fibrosuppressive effects on smooth muscle cells from human coronary arteries.

Cited by 54 publications

References 46 publications

Modulation of Differentiation-related Gene 1 Expression by Cell Cycle Blocker Mimosine, Revealed by Proteomic Analysis

Modulation of Differentiation-related Gene 1 Expression by Cell Cycle Blocker Mimosine, Revealed by Proteomic Analysis

Genomic instability in the type II TGF-beta1 receptor gene in atherosclerotic and restenotic vascular cells.

Endoglin Upregulation in the Liver after Bile Duct Ligation in Rats

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