Plasmolipin and Its Role in Cell Processes

Abstract The mechanisms involved in the origin and development of malignant and neurodegenerative diseases are an important area of modern biomedicine. A crucial task is to identify new molecular markers that are associated with rearrangements of intracellular signaling and can be used for prognosis and the development of effective treatment approaches. The proteolipid plasmolipin (PLLP) is a possible marker. PLLP is a main component of the myelin sheath and plays an important role in the development and normal function of the nervous system. PLLP is involved in intracellular transport, lipid raft formation, and Notch signaling. PLLP is presumably involved in various disorders, such as cancer, schizophrenia, Alzheimer’s disease, and type 2 diabetes mellitus. PLLP and its homologs were identified as possible virus entry receptors. The review summarizes the data on the PLLP structure, normal functions, and role in diseases.

Download Full-text

Abstract 424: Mechanisms of Restenosis in Type 2 Diabetes Mellitus

Arteriosclerosis Thrombosis and Vascular Biology ◽

10.1161/atvb.33.suppl_1.a424 ◽

2013 ◽

Vol 33 (suppl_1) ◽

Author(s):

Hongfeng Wang ◽

Judy R Kersten ◽

Jeffrey M Toth ◽

John F LaDisa

Keyword(s):

Diabetes Mellitus ◽

Type 2 Diabetes ◽

Type 2 Diabetes Mellitus ◽

Abdominal Aorta ◽

Intracellular Signaling ◽

Vascular Remodeling ◽

Neointimal Hyperplasia ◽

Cross Linking ◽

Collagen Cross Linking

Stents are widely employed to decrease cardiovascular risk in patients with type 2 diabetes mellitus (T2DM); however, restenosis limits their success. Mechanisms responsible for restenosis in T2DM are incompletely elucidated; however, low wall shear stress (WSS) and altered intracellular signaling likely contribute. We tested the hypothesis that neointimal hyperplasia (NH) after bare-metal stenting in T2DM is due to vascular remodeling (enhanced formation of advanced glycation end-products (AGEs), increased downstream vascular resistance (DVR), and decreased WSS) in T2DM; and that decreasing AGEs with ALT-711 (Alagebrium) mitigates this response. Stents were implanted into the abdominal aorta of Zucker lean (ZL), obese (ZO), and diabetic (ZD) rats. After 21 days, blood flow and pressure data were recorded; and the stented region was sectioned for NH quantification or casted and imaged for WSS distributions by computational fluid dynamics modeling. Arterial segments (thoracic and abdominal aorta, carotid, iliac, femoral and arterioles) were harvested to detect AGEs related collagen cross-linking, and protein expression including TGFβ and receptor for AGE (RAGE). DVR was elevated, whereas, WSS was significantly decreased in ZD compared to ZL and ZO rats, respectively (14.5±1.9 vs 30.6±1.6 and 25.4±2.2dyn/cm 2 ; mean±SEM p<0.05). Intra-strut thickness (NH) was increased in ZO but not ZD rats. ALT-711 reduced DVR in ZD rats (15.6±2.5x10 5 to 8.39±0.6x10 5 dyn·s/cm 5 ), decreased NH (ZL: 7.7±1.0 to 4.3±0.9%; ZO: 12.0±1.5 to 4.9±0.8%; ZD: 9.4±0.7 to 3.7±0.4%) and restored WSS in all rats. Increases in AGEs related collagen cross-linking were present in the arterioles of ZD rats, but reduced by treatment with ALT-711. No differences in RAGE or TGFβ expression were observed in treated compared to untreated rats. In conclusion, ALT-711 decreased AGEs related collagen cross-linking, DVR, and normalized intra-stent WSS in rats with T2DM. These findings suggest that vascular remodeling may play an important role in modulating restenosis. Although TGFβ and RAGE expression did not appear to be modified by ALT-711, other intracellular signaling pathways that influence restenosis during T2DM remain to be explored.

Download Full-text

Consumption of Virgin Olive Oil Influences Membrane Lipid Composition and Regulates Intracellular Signaling in Elderly Adults With Type 2 Diabetes Mellitus

The Journals of Gerontology Series A ◽

10.1093/gerona/62.3.256 ◽

2007 ◽

Vol 62 (3) ◽

pp. 256-263 ◽

Cited By ~ 26

Author(s):

J. S. Perona ◽

O. Vogler ◽

J. M. Sanchez-Dominguez ◽

E. Montero ◽

P. V. Escriba ◽

...

Keyword(s):

Diabetes Mellitus ◽

Type 2 Diabetes ◽

Type 2 Diabetes Mellitus ◽

Lipid Composition ◽

Intracellular Signaling ◽

Virgin Olive Oil ◽

Membrane Lipid ◽

Elderly Adults ◽

Membrane Lipid Composition

Download Full-text

qPCR Analysis Reveals Association of Differential Expression of SRR, NFKB1, and PDE4B Genes With Type 2 Diabetes Mellitus

Frontiers in Endocrinology ◽

10.3389/fendo.2021.774696 ◽

2022 ◽

Vol 12 ◽

Author(s):

Waseem Raza ◽

Jinlei Guo ◽

Muhammad Imran Qadir ◽

Baogang Bai ◽

Syed Aun Muhammad

Keyword(s):

Diabetes Mellitus ◽

Type 2 Diabetes ◽

Type 2 Diabetes Mellitus ◽

Signaling Pathway ◽

Intracellular Transport ◽

Expression Profiles ◽

Transcriptional Factors ◽

System Level ◽

Protein Motifs

BackgroundType 2 diabetes mellitus (T2DM) is a heterogeneous, metabolic, and chronic condition affecting vast numbers of the world’s population. The related variables and T2DM associations have not been fully understood due to their diverse nature. However, functional genomics can facilitate understanding of the disease. This information will be useful in drug design, advanced diagnostic, and prognostic markers.AimTo understand the genetic causes of T2DM, this study was designed to identify the differentially expressed genes (DEGs) of the disease.MethodsWe investigated 20 publicly available disease-specific cDNA datasets from Gene Expression Omnibus (GEO) containing several attributes including gene symbols and clone identifiers, GenBank accession numbers, and phenotypic feature coordinates. We analyzed an integrated system-level framework involving Gene Ontology (GO), protein motifs and co-expression analysis, pathway enrichment, and transcriptional factors to reveal the biological information of genes. A co-expression network was studied to highlight the genes that showed a coordinated expression pattern across a group of samples. The DEGs were validated by quantitative PCR (qPCR) to analyze the expression levels of case and control samples (50 each) using glyceraldehyde 3-phosphate dehydrogenase (GAPDH) as the reference gene.ResultsFrom the list of 50 DEGs, we ranked three T2DM-related genes (p < 0.05): SRR, NFKB1, and PDE4B. The enriched terms revealed a significant functional role in amino acid metabolism, signal transduction, transmembrane and intracellular transport, and other vital biological functions. DMBX1, TAL1, ZFP161, NFIC (66.7%), and NR1H4 (33.3%) are transcriptional factors associated with the regulatory mechanism. We found substantial enrichment of insulin signaling and other T2DM-related pathways, such as valine, leucine and isoleucine biosynthesis, serine and threonine metabolism, adipocytokine signaling pathway, P13K/Akt pathway, and Hedgehog signaling pathway. The expression profiles of these DEGs verified by qPCR showed a substantial level of twofold change (FC) expression (2−ΔΔCT) in the genes SRR (FC ≤ 0.12), NFKB1 (FC ≤ 1.09), and PDE4B (FC ≤ 0.9) compared to controls (FC ≥ 1.6). The downregulated expression of these genes is associated with pathophysiological development and metabolic disorders.ConclusionThis study would help to modulate the therapeutic strategies for T2DM and could speed up drug discovery outcomes.

Download Full-text