Introduction: Nuclear accumulation of a mutant form of the nuclear protein Lamin-A, called Progerin (PG) or Lamin AΔ50, occurs in Hutchinson-Gilford Progeria Syndrome (HGPS) or Progeria, an accelerated aging disease. One of the main symptoms of this genetic disorder is a loss of sub-cutaneous fat due to a dramatic lipodystrophy.
Methods: We stably induced the expression of human PG and GFP -Green Fluorescent Protein- as control in 3T3L1 cells using a lentiviral system to study the effect of PG expression in the differentiation capacity of this cell line, one of the most used adipogenic models. Quantitative proteomics (iTRAQ) was done to study the effect of the PG accumulation. Several of the modulated proteins were validated by immunoblotting and real-time PCR. Mitochondrial function was analyzed by measurement of a) the mitochondrial basal activity, b) the superoxide anion production and c) the individual efficiency of the different complex of the respiratory chain.
Results: We found that over-expression PG by lentiviral gene delivery leads to a decrease in the proliferation rate and to defects in adipogenic capacity when compared to the control. Quantitative proteomics analysis showed 181 proteins significantly (p<0.05) modulated in PG-expressing preadipocytes. Mitochondrial function is impaired in PG-expressing cells. Specifically, we have detected an increase in the activity of the complex I and an overproduction of Superoxide anion. Incubation with Reactive Oxygen Species (ROS) scavenger agents drives to a decrease in autophagic proteolysis as revealed by LC3-II/LC3-I ratio.
Conclusion: PG expression in 3T3L1 cells promotes changes in several Biological Processes, including structure of cytoskeleton, lipid metabolism, calcium regulation, translation, protein folding and energy generation by the mitochondria. Our data strengthen the contribution of ROS accumulation to the premature aging phenotype and establish a link between mitochondrial dysfunction and loss of proteostasis in HGPS.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4487579 | PMC |
| http://dx.doi.org/10.1186/s13287-015-0110-5 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Repair effect analysis of mesenchymal stem cell conditioned media from multiple sources on HUVECs damaged by high glucose.
Clin Proteomics
December 2024
Key Laboratory of Epigenetic Regulation and Intervention, Institute of Biophysics, Chinese Academy of Sciences, Beijing, 100101, China.
Background: The therapeutic potential of mesenchymal stem cells (MSCs) may be partly attributed to their secretion growth factors, cytokines and chemokines. In various preclinical studies, the use of MSC-conditioned media (CM) has demonstrated promising potential for promoting vascular repair.
Methods: To gain a comprehensive understanding of the variations in conditioned media derived from different sources of mesenchymal stem cells (MSCs) including umbilical cord, adipose and bone marrow, we investigated their reparative effects on human umbilical vein endothelial cells (HUVECs) subjected to damage induced by high glucose.
Quantitative site-specific N-glycosylation analysis reveals IgG glyco-signatures for pancreatic cancer diagnosis.
Clin Proteomics
December 2024
Department of Pancreatic Surgery and Institutes for Systems Genetics, West China Hospital, Sichuan University, Keyuan 4th Road, Gaopeng Avenue, Hi-tech Zone, Chengdu, Sichuan, 610041, China.
Background: Pancreatic cancer is a highly aggressive tumor with a poor prognosis due to a low early detection rate and a lack of biomarkers. Most of pancreatic cancer is pancreatic ductal adenocarcinoma (PDAC). Alterations in the N-glycosylation of plasma immunoglobulin G (IgG) have been shown to be closely associated with the onset and development of several cancers and could be used as biomarkers for diagnosis.
View Article and Find Full Text PDFRevealing novel protein interaction partners of glyphosate in Escherichia coli.
Environ Int
December 2024
Department of Molecular Toxicology, Helmholtz-Centre for Environmental Research GmbH (UFZ), Leipzig, Germany.
Despite all debates about its safe use, glyphosate remains the most widely applied active ingredient in herbicide products, with renewed approval in the European Union until 2033. Non-target organisms are commonly exposed to glyphosate as a matter of its mode of application, with its broader environmental and biological impacts remaining under investigation. Glyphosate displays structural similarity to phosphoenolpyruvate (PEP), thereby competitively inhibiting the 5-enolpyruvylshikimate-3-phosphate synthase (EPSPS), crucial for the synthesis of aromatic amino acids in plants, fungi, bacteria, and archaea.
View Article and Find Full Text PDFCardio-metabolic and cytoskeletal proteomic signatures differentiate stress hypersensitivity in dystrophin-deficient mdx mice.
J Proteomics
December 2024
School of Biological Sciences, University of Canterbury, Christchurch 8041, New Zealand; Institute for Physical Activity and Nutrition, School of Exercise and Nutrition Sciences, Deakin University, Geelong, Australia; Department of Medicine, University of Otago, Christchurch 8014, New Zealand; Biomolecular Interaction Centre, School of Biological Sciences, University of Canterbury, Christchurch 8140, New Zealand; Maurice Wilkins Centre for Molecular Biodiscovery, Auckland 1010, New Zealand. Electronic address:
Extreme heterogeneity exists in the hypersensitive stress response exhibited by the dystrophin-deficient mdx mouse model of Duchenne muscular dystrophy. Because stress hypersensitivity can impact dystrophic phenotypes, this research aimed to understand the peripheral pathways driving this inter-individual variability. Male and female mdx mice were phenotypically stratified into "stress-resistant" or "stress-sensitive" groups based on their response to two laboratory stressors.
View Article and Find Full Text PDFComprehensive site- and structure-specific profiling of N-glycosylation of edible bird's nest (EBN) proteome using label-free quantitative glycoproteomics.
Food Chem
December 2024
Chinese Academy of Inspection and Quarantine, Beijing 100176, People's Republic of China. Electronic address:
Glycoproteins, which are involved in numerous biological functions, are among the most critical functional ingredients in an edible bird's nest (EBN). To gain a comprehensive understanding of the glycoprotein species within EBN, a label-free, site-specific glycoproteomic approach was used to analyze their N-glycoproteins, N-glycopeptides, and N-glycans systematically. A total of 127 N-glycoproteins were identified in EBN, of which 72 were found in house-EBN and 63 in cave-EBN, yielding 4195 and 5649 glycopeptides, respectively.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!