ORCID Profile
0000-0002-8529-4217
Current Organisations
Justus-Liebig-Universität Giessen
,
Justus Liebig Universitat Giessen
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Publisher: MDPI AG
Date: 26-07-2021
DOI: 10.3390/IJMS22157967
Abstract: Changes in plasma membrane curvature and intracellular ionic strength are two key features of cell volume perturbations. In this hypothesis we present a model of the responsible molecular apparatus which is assembled of two molecular motors [non-muscle myosin II (NMMII) and protrusive actin polymerization], a spring [a complex between the plasma membrane (PM) and the submembrane actin-based cytoskeleton (smACSK) which behaves like a viscoelastic solid] and the associated signaling proteins. We hypothesize that this apparatus senses changes in both the plasma membrane curvature and the ionic strength and in turn activates signaling pathways responsible for regulatory volume increase (RVI) and regulatory volume decrease (RVD). During cell volume changes hydrostatic pressure (HP) changes drive alterations in the cell membrane curvature. HP difference has opposite directions in swelling versus shrinkage, thus allowing distinction between them. By analogy with actomyosin contractility that appears to sense stiffness of the extracellular matrix we propose that NMMII and actin polymerization can actively probe the transmembrane gradient in HP. Furthermore, NMMII and protein-protein interactions in the actin cortex are sensitive to ionic strength. Emerging data on direct binding to and regulating activities of transmembrane mechanosensors by NMMII and actin cortex provide routes for signal transduction from transmembrane mechanosensors to cell volume regulatory mechanisms.
Publisher: MDPI AG
Date: 26-05-2021
Abstract: Myocardial injury is associated with inflammation and fibrosis. Cardiac myosin-binding protein-C (cMyBP-C) is cleaved by µ-calpain upon myocardial injury, releasing C0-C1f, an N-terminal peptide of cMyBP-C. Previously, we reported that the presence of C0-C1f is pathogenic within cardiac tissue and is able to activate macrophages. Fibroblasts also play a crucial role in cardiac remodeling arising from ischemic events, as they contribute to both inflammation and scar formation. To understand whether C0-C1f directly modulates fibroblast phenotype, we analyzed the impact of C0-C1f on a human fibroblast cell line in vitro by performing mRNA microarray screening, immunofluorescence staining, and quantitative real-time PCR. The underlying signaling pathways were investigated by KEGG analysis and determined more precisely by targeted inhibition of the potential signaling cascades in vitro. C0-C1f induced pro-inflammatory responses that might delay TGFβ-mediated myofibroblast conversion. TGFβ also counteracted C0-C1f-mediated fibroblast activation. Inhibition of TLR4 or NFκB as well as the delivery of miR-146 significantly reduced C0-C1f-mediated effects. In conclusion, C0-C1f induces inflammatory responses in human fibroblasts that are mediated via TRL4 signaling, which is decreased in the presence of TGFβ. Specific targeting of TLR4 signaling could be an innovative strategy to modulate C0-C1f-mediated inflammation.
Publisher: MDPI AG
Date: 10-02-2022
DOI: 10.3390/MEMBRANES12020205
Abstract: Chronic low-grade vascular inflammation and endothelial dysfunction significantly contribute to the pathogenesis of cardiovascular diseases. In endothelial cells (ECs), anti-inflammatory or pro-inflammatory signaling can be induced by different patterns of the fluid shear stress (SS) exerted by blood flow on ECs. Laminar blood flow with high magnitude is anti-inflammatory, while disturbed flow and laminar flow with low magnitude is pro-inflammatory. Endothelial mechanosensors are the key upstream signaling proteins in SS-induced pro- and anti-inflammatory responses. Being transmembrane proteins, mechanosensors, not only experience fluid SS but also become regulated by the biomechanical properties of the lipid bilayer and the cytoskeleton. We review the apparent effects of pro-inflammatory factors (hypoxia, oxidative stress, hypercholesterolemia, and cytokines) on the biomechanics of the lipid bilayer and the cytoskeleton. An analysis of the available data suggests that the formation of a vicious circle may occur, in which pro-inflammatory cytokines enhance and attenuate SS-induced pro-inflammatory and anti-inflammatory signaling, respectively.
Publisher: MDPI AG
Date: 03-06-2021
Abstract: Endothelial cells (ECs) are exposed to molecular dioxygen and its derivative reactive oxygen species (ROS). ROS are now well established as important signaling messengers. Excessive production of ROS, however, results in oxidative stress, a significant contributor to the development of numerous diseases. Here, we analyze the experimental data and theoretical concepts concerning positive pro-survival effects of ROS on signaling pathways in endothelial cells (ECs). Our analysis of the available experimental data suggests possible positive roles of ROS in induction of pro-survival pathways, downstream of the Gi-protein-coupled receptors, which mimics insulin signaling and prevention or improvement of the endothelial dysfunction. It is, however, doubtful, whether ROS can contribute to the stabilization of the endothelial barrier.
Publisher: Elsevier BV
Date: 11-2018
DOI: 10.1016/J.BIOSYSTEMS.2018.08.007
Abstract: Myriads of signaling pathways in a single cell function to achieve the highest spatio-temporal integration. Data are accumulating on the role of electromechanical soliton-like waves in signal transduction processes. Theoretical studies strongly suggest feasibility of both classical and quantum computing involving microtubules. A theoretical study of the role of the complex composed of the plasma membrane and the microtubule-based cytoskeleton as a system that transmits, stores and processes information. Theoretical analysis presented here refers to (i) the Penrose-Hameroff theory of consciousness (Orchestrated Objective Reduction Orch OR), (ii) the description of the centrosome as a reference system for construction of the 3D map of the cell proposed by Regolini, (iii) the Heimburg-Jackson model of the nerve pulse propagation along axons' lipid bilayer as soliton-like electro-mechanical waves. The ideas presented in this paper provide a qualitative model for the decision-making processes in a living cell undergoing a differentiation process. This paper paves the way for the real-time live-cell observation of information processing by microtubule-based cytoskeleton and cell fate decision making.
No related grants have been discovered for Muhammad Aslam.