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Mechanobiology of Cardiac Fibroblasts
Published in Jiro Nagatomi, Eno Essien Ebong, Mechanobiology Handbook, 2018
Peter A. Galie, Jan P. Stegemann
Directly measuring the cellular response to mechanical load is complicated by several factors that affect the phenotype of cardiac fibroblasts. For example, cardiac fibroblasts isolated from tissue typically begin to spontaneously differentiate to a myofibroblast phenotype. Studies have shown that this transition may be related to increased activation of protein kinase A through the G protein coupled receptor–adenylyl cyclase–cAMP pathway.15 Moreover, the cells appear to be sensitive to the concentration of serum used in the culture medium. Serum deprivation has been shown to not only affect the expression of SMA.15 but also the viability and ECM production of cardiac fibroblasts.16,17 Another recent study observed that the response of cardiac fibroblasts to cyclic mechanical loading depended upon the serum concentration of the culture media.18 The data indicated that the cell response to cyclic loading was negligible when cultured in 1% FBS, but became significant in the presence of 10% serum. In this case, the cellular response was characterized by the amount of procollagen produced by the cells, as well as labeled thymidine incorporation as a measure of cell proliferation.
Stem Cell Engineering Using Bioactive Molecules for Bone-Regenerative Medicine
Published in Gilson Khang, Handbook of Intelligent Scaffolds for Tissue Engineering and Regenerative Medicine, 2017
Adenosine is an endogenous signaling nucleoside composed of an adenine molecule attached to a ribose sugar (MW: 267.2 Da). Adenosine, like many other mediators of angiogenesis, also contributes to bone-related signaling. Agonists of all four adenosine receptors (A1, A2a A2b, and A3) enhance proliferation of human primary osteoblast cells in vitro, while associated antagonists abrogate these effects.125 Agonism of the A2a receptor inhibits macrophage colony–stimulating factor (M-CSF)/RANKL-induced osteoclast differentiation as measured by cathepsin K, NFATc1, and OPN. Adenosine can be converted to cyclic adenosine monophosphate (cAMP) through a series of biochemical synthesis reactions that ends with the conversion of adenosine triphosphate to cAMP by adenylyl cyclase. While adenosine has been associated with both angiogenic and osteogenic effects, cAMP has been mostly explored as a means for enhancing bone formation. Codelivery of dibutyryl cAMP (dbcAMP), a cell-permeable cAMP analogue, with BMP-4 to mouse stromal cells results in enhanced expression of ALP in a dbcAMP dose-dependent manner. Another cAMP analogue, 6-Bnz-cAMP, was recently used to enhance osteogenic differentiation of mouse osteoblast-like cells, while enhancing RUNX2 expression, ALP activity, osteocalcin and OPN expression, and calcium mineralization.126
Hyperlipidemia and male infertility
Published in Egyptian Journal of Basic and Applied Sciences, 2021
Zainab Bubakr Hamad Zubi, Hamad Abdulsalam Hamad Alfarisi
Mammalian sperm cell membrane has a lipid bilayer consists of phospholipids and cholesterol. During passage of sperm from the testes to the female genital tract, sperm membrane undergoes several modifications. Membrane lipids particularly cholesterol are responsible for the physiological alterations in the membrane fluidity and cell responsiveness to the environment [40]. Cholesterol of sperm plasma membrane regulates membrane permeability, lateral mobility of integral proteins and functional receptors within the membrane. Loss of cholesterol from the membrane is responsible for destabilization of the membrane during capacitation [44]. Capacitation is the functional maturation of the sperm which takes place within the female genital tract. It is essential for the sperm ability to fertilize an egg. It involves changes in the sperm head and flagellum including the ability of sperm to undergo acrosomal reaction and acquisition of motility hyperactivation [45]. The initial step toward the capacitation is the removal of sperm external coating-proteins that protect the sperm on its path to oocyte and prevent early occurrence of acrosomal reaction [44]. Cholesterol efflux from the sperm membrane causes a decrease in the cholesterol/phospholipid ratio which leads to changes in the membrane fluidity and causes membrane protein redistribution that required for capacitation [46]. It is also important for signaling mechanisms that regulate capacitation process. Signaling mechanisms can be initiated through the cholesterol loss via two mechanisms: 1) an interaction between membrane proteins which occurs as a subsequent to the increase in the membrane fluidity and 2) freeing of certain signaling molecules from their interaction with cavolin giving them the ability to form specific signaling complexes [47]. Cholesterol efflux is an early event in the capacitation followed by a reduction in the cholesterol/phospholipid ratio which changes the membrane dynamics and increases its permeability to bicarbonate and calcium ions. This is followed by the activation of adenylyl cyclase and increase production of cyclic adenosine monophosphate (cAMP). A signal cascade initiated through activation of protein kinase A (PKA) which phosphorylates sperm protein tyrosine residue. Finally, the sperm acquire hyperactive motility and the ability to bind to zona pellucida to undergo the acrosomal reaction [48]. Hypercholesterolemia alters the concentration and distribution of cholesterol of sperm plasma membrane and subsequently reduces the acrosomal reaction and capacitation [40,41]. High cholesterol level inhibits capacitation either through its direct effect on certain surface proteins that have roles in signaling transduction, or indirectly via restricting the conformational changes of sperm surface proteins and consequently decreases their activity [47].