Apoptosis of human endothelial cells is accompanied by proteolytic processing of latent TGF-β binding proteins and activation of TGF-β

Solovyan, V. T.; Keski‐Oja, Jorma

doi:10.1038/sj.cdd.4401618

Cited by 26 publications

(22 citation statements)

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“…The suppressive effect of AEBSF on the level of PAI-1 promoter (luciferase) activity strongly suggests the involvement of serine protease(s) in the activation of ECM-associated TGF-b during Mv1Lu cell apoptosis. This is in line with our recent results on the pivotal role of serine proteases in the release and activation of ECM-located TGF-b during apoptosis of endothelial cells (Solovyan and Keski-Oja, 2005).…”

Section: Discussionsupporting

confidence: 89%

“…The results are suggestive of a positive feedback loop, which occurs between TGF-b activation and apoptotic cell death, and emphasize TGF-b activation as a component of the apoptotic response. Our recent report on the activation of endogenous TGF-b during apoptosis of human vascular endothelial cells (Solovyan and Keski-Oja, 2005) further implies that the activation of TGF-b is a common feature of the apoptotic response in different cell types.…”

Section: Discussionmentioning

confidence: 95%

“…Whether the activated TGF-b directly drives caspase activation during apoptosis of Mv1Lu cells needs further elucidation. (Solovyan and Keski-Oja, 2005). Activated TGF-b modulates the apoptotic response of target cells via initiation of intracellular signaling (4) leading to attenuation of cell death of HUVECs (Solovyan and Keski-Oja, 2005), or to potentiation of Mv1Lu cell death (current results) (5), depending apparently on the sensitivity of the cells to the cytokine.…”

Section: Discussionmentioning

confidence: 95%

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Proteolytic activation of latent TGF‐β precedes caspase‐3 activation and enhances apoptotic death of lung epithelial cells

Solovyan

Keski‐Oja

2006

Journal Cellular Physiology

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Transforming growth factors beta (TGF-betas) are multifunctional cytokines, which are secreted in latent forms in large latent TGF-beta complexes (LL-TGF-beta) with subsequent deposition to the extracellular matrix (ECM). While a variety of mechanisms capable of activating latent TGF-beta in vitro have been described, the physiological conditions, which promote the activation of TGF-beta in vivo are poorly understood. Mink lung epithelial cells (Mv1Lu) are a widely used model for evaluation of the effects of exogenous TGF-beta both in transcriptional and growth inhibitor assays. We find here that apoptosis of Mv1Lu cells, induced either by staurosporine or serum deprivation, is accompanied by proteolytic processing of LL-TGF-beta and the activation of endogenous TGF-beta. Activation of TGF-beta preceded caspase-3 activation and was almost completely suppressed by the serine protease inhibitor, AEBSF. Both exogenous and endogenously activated TGF-betas were able to enhance the apoptotic response of Mv1Lu cells leading to potentiation of cell death. Potentiation of cell death by activated TGF-beta was associated with downregulation of Akt and p38 MAPK, which were both activated at the initial stages of Mv1Lu apoptosis and were suppressed by exogenous TGF-beta. Pharmacological interruption of either phosphoinositide-3-kinase (PI-3K)/Akt or p38 MAPK signaling by the specific inhibitors mimicked the effect of TGF-beta leading to potentiation of cell death. Current results suggest that proteolytic activation of endogenous TGF-beta is a component of the apoptotic response, capable of modulating the death of Mv1Lu cells by inhibition of both PI-3K/Akt and p38 MAPK-dependent survival pathways.

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Section: Discussionsupporting

confidence: 89%

Section: Discussionmentioning

confidence: 95%

Section: Discussionmentioning

confidence: 95%

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Proteolytic activation of latent TGF‐β precedes caspase‐3 activation and enhances apoptotic death of lung epithelial cells

Solovyan

Keski‐Oja

2006

Journal Cellular Physiology

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“…Signaling by TGF-β is required for T. cruzi replication in epithelial cells (47). Apart from the properties of the parasite (47), apoptosis could drive this process, since apoptotic cells release TGF-β (48,49), and TGF-β induces apoptosis in epithelial cells and hepatocytes (50). In addition, TGF-β appears to be important for parasite replication in cardiac fibroblasts and myocytes, as well as fibrosis and cardiac remodeling in the course of infection (51).…”

Section: The Chronic Phase: An Equilibrium Between Parasite Killing Amentioning

confidence: 99%

“…Center, Penetration and replication of T. cruzi in epithelial cells require signaling of TGF-β through TGF-β receptors TβRI or TβRII (47). Amplifying mechanism: apoptotic cell death releases either active or latent TGF-β into the extracellular medium (48,49). In addition, TGF-β induces apoptosis in epithelial cells and hepatocytes (50).…”

Section: The Chronic Phase: An Equilibrium Between Parasite Killing Amentioning

confidence: 99%

Evasion of immune responses by Trypanosoma cruzi, the etiological agent of Chagas disease

DosReis

2011

Braz J Med Biol Res

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Infection with the protozoan parasite Trypanosoma cruzi leads to Chagas disease, which affects millions of people in Latin America. Infection with T. cruzi cannot be eliminated by the immune system. A better understanding of immune evasion mechanisms is required in order to develop more effective vaccines. During the acute phase, parasites replicate extensively and release immunomodulatory molecules that delay parasite-specific responses mediated by T cells. This immune evasion allows the parasite to spread in the host. In the chronic phase, parasite evasion relies on its replication strategy of hijacking the TGF-β signaling pathway involved in inflammation and tissue regeneration. In this article, the mechanisms of immune evasion described for T. cruzi are reviewed.

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The granule size distribution in an anammox‐based granular sludge reactor affects the conversion—Implications for modeling

Volcke

Picioreanu

Baets

et al. 2012

Biotech & Bioengineering

100

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Mathematical models are useful tools to optimize the performance of granular sludge reactors. In these models, typically a uniform granule size is assumed for the whole reactor, even though in reality the granules follow a size distribution and the granule size as such affects the process performance. This study assesses the effect of the granule size distribution on the performance of a granular sludge reactor in which autotrophic nitrogen removal is realized through one-stage partial nitritation-anammox. A comparison is made between different approaches to deal with particle size distributions in one-dimensional biofilm models, from the use of a single characteristic diameter to applying a multiple compartment model. The results show a clear impact on the conversion efficiency of the way in which particle size distribution is modeled, resulting from the effect of the granule size on the competition between nitrite oxidizing and anammox bacteria and from the interaction between granules of different sizes in terms of the exchange of solutes. Whereas the use of a uniform granule size is sufficient in case only the overall reactor behavior needs to be assessed, taking into account the detailed granule size distribution is required to study the solute exchange between particles of different sizes. For the latter purpose, the application of the widespread software package Aquasim is limited and the development of dedicated software applications is required.

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Apoptosis of human endothelial cells is accompanied by proteolytic processing of latent TGF-β binding proteins and activation of TGF-β

Cited by 26 publications

References 50 publications

Proteolytic activation of latent TGF‐β precedes caspase‐3 activation and enhances apoptotic death of lung epithelial cells

Proteolytic activation of latent TGF‐β precedes caspase‐3 activation and enhances apoptotic death of lung epithelial cells

Evasion of immune responses by Trypanosoma cruzi, the etiological agent of Chagas disease

The granule size distribution in an anammox‐based granular sludge reactor affects the conversion—Implications for modeling

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