Increased plasticity of the nuclear envelope and hypermobility of telomeres due to the loss of A–type lamins

Vos, Winnok H. De; Houben, Frederik; Hoebe, Ron A.; Hennekam, Raoul C. M.; Engelen, B.G.M. van; Manders, Erik M. M.; Ramaekers, Frans C. S.; Broers, Jos L. V.; Oostveldt, Patrick Van

doi:10.1016/j.bbagen.2010.01.002

Cited by 73 publications

(66 citation statements)

References 66 publications

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“…It disrupts mitosis and induces DnA damage in vascular smooth muscle cells (VSMCs), leading to mitotic failure, genomic instability, and premature senescence (35). lamins constitute a class of intermediate filaments with structural and functional roles, closely associated with the inner nuclear membrane, nuclear pore complexes and chromatine (36).…”

Section: Discussionmentioning

confidence: 99%

Two-dimensional gel electrophoresis analysis of the leiomyoma interstitial fluid reveals altered protein expression with a possible involvement in pathogenesis

et al. 2015

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Abstract. Uterine leiomyoma is the most common smooth benign neoplasm. In the present study, we analyzed the global interstitial fluid (IF) profile of leiomyoma vs. normal myometrium to identify protein dysregulation involved in leiomyoma pathogenesis. Two-dimensional gel electrophoresis and mass spectrometry were used to generate and compare the global interstitial fluid profiles of the leiomyoma and of the normal tissue. Two proteins were validated by immunohistochemistry. By comparing the interstitial fluid profile of the leiomyoma with that of the normal myometrium, the levels of seven proteins were found to be significantly different: four structural organization proteins (desmin, prelamin-A/C, transgelin and α-actinin-1), an inflammatory response (α1-antitrypsin), a response to oxidative stress (peroxiredoxin-2), and a folding protein (heat shock 70 kDa protein 1A/1B). Desmin, α1-antitrypsin and peroxiredoxin-2 were upregulated in the leiomyoma, whereas heat shock 70 kDa protein 1A/1B, α-actinin-1, prelamin-A/C and transgelin were downregulated. Desmin and α1-antitrypsin were further validated by immunohistochemistry. By identifying proteins with altered expression levels compared to the myometrium from several pathways of the leiomyoma pathogenesis, we found the leiomyoma interstitial fluid to have a characteristic proteomic profile. A better appreciation of the pathophysiology of the disease can be useful in the development of conservative treatments that serve as viable alternatives to hysterectomy.

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Section: Discussionmentioning

confidence: 99%

Two-dimensional gel electrophoresis analysis of the leiomyoma interstitial fluid reveals altered protein expression with a possible involvement in pathogenesis

et al. 2015

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“…as nuclei from HGPs cells are more rigid (19) and have a disturbed mechanotransduction (20), these cells may become less or differently responsive to the effects of microgravity. In addition, HGPs cells display a strongly compromised dna damage response (8).…”

Section: Discussionmentioning

confidence: 99%

Multiplexed profiling of secreted proteins for the detection of potential space biomarkers

et al. 2010

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Abstract. Space travel exposes astronauts to a plethora of potentially detrimental conditions, such as cosmic radiation and microgravity. as both factors are hard to simulate on earth, present knowledge remains limited. However, this knowledge is of vital importance, making space flight experiments a necessity for determining the biological effects and the underlying biochemical processes, especially when keeping future long-term interplanetary missions in mind. instead of estimating the long-term effects, which usually implicate severe endpoints (e.g., cancer) and which are often difficult to attribute, research has shifted to finding representative biomarkers for rapid and sensitive detection of individual radiosensitivity. in this context, an appealing set of candidate markers is the group of secreted proteins, as they exert an intercellular signaling function and are easy to assess. We screened a subset of secreted proteins in cells exposed to space travel by means of multiplex bead array analysis. To determine the cell-specific signatures of the secreted molecules, we compared the conditioned medium of normal fibroblast cells to fibroblasts isolated from a patient with Hutchinson-Gilford Progeria syndrome, which are known to have a perturbed nuclear architecture and dna damage response. out of the 88 molecules screened, 20 showed a significant level increase or decrease, with a differential response to space conditions between the two cell types. among the molecules that were retained, which may prove to be valuable biomarkers, are apolipoprotein c-iii, plasminogen activator inhibitor type 1, β-2-microglobulin, ferritin, MMP-3, TIMP-1 and VEGF.

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“…Lamin family proteins are components of the nuclear lamina, which in turn provides support to the nucleus and are central to maintenance of nuclear integrity. It has been shown in literature that lamins may play an important role in chromatin organization and telomere dynamics (31). Furthermore, it is suggested that Prelamin-A/C accumulation plays a role in smooth-muscle cell senescence by disrupting mitosis and inducing DNA damage in vascular smooth-muscle cells causing genomic instability and premature senescence.…”

Section: Pathway Analysis Of the Subgroupsmentioning

confidence: 99%

Discovery-Based Protein Expression Profiling Identifies Distinct Subgroups and Pathways in Leiomyosarcomas

Kirik

Hansson

Krogh³

et al. 2014

Molecular Cancer Research

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Soft tissue sarcomas (STS) are malignant tumors of mesenchymal origin. A substantial portion of these tumors exhibits complex karyotypes and lack characterized chromosomal aberrations. Owing to such properties, both histopathologic and molecular classification of these tumors has been a significant challenge. This study examines the protein expression of a large number of human STS, including subtype heterogeneity, using two-dimensional gel proteomics. In addition, detailed proteome profiles of a subset of pleomorphic STS specimens using an in-depth mass-spectrometry approach identified subgroups within the leiomyosarcomas with distinct protein expression patterns. Pathways analysis indicates that key biologic nodes like apoptosis, cytoskeleton remodeling, and telomere regulation are differentially regulated among these subgroups. Finally, investigating the similarities between protein expression of leiomyosarcomas and undifferentiated pleomorphic sarcomas (UPS) revealed similar protein expression profiles for these tumors, in comparison with pleomorphic leiomyosarcomas.

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Increased plasticity of the nuclear envelope and hypermobility of telomeres due to the loss of A–type lamins

Cited by 73 publications

References 66 publications

Two-dimensional gel electrophoresis analysis of the leiomyoma interstitial fluid reveals altered protein expression with a possible involvement in pathogenesis

Two-dimensional gel electrophoresis analysis of the leiomyoma interstitial fluid reveals altered protein expression with a possible involvement in pathogenesis

Multiplexed profiling of secreted proteins for the detection of potential space biomarkers

Discovery-Based Protein Expression Profiling Identifies Distinct Subgroups and Pathways in Leiomyosarcomas

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