An innovative intermittent hypoxia model for cell cultures allowing fast PO2 oscillations with minimal gas consumption
In conclusion, we have established a new device to perform rapid intermittent hypoxia cycles in cell cultures, with minimal gas consumption and the possibility to expose several culture dishes simultaneously. This device will allow functional studies of the consequences of IH and deciphering of the molecular biology of IH at the cellular level using oxygen cycles that are clinically relevant to OSA. (Source: AJP: Cell Physiology)
Source: AJP: Cell Physiology - October 9, 2017 Category: Cytology Authors: Minoves, M., Morand, J., Perriot, F., Chatard, M., Gonthier, B., Lemarie, E., Menut, J.-B., Polak, J., Pepin, J.-L., Godin-Ribuot, D., Briancon-Marjollet, A. Tags: METHODS IN CELL PHYSIOLOGY Source Type: research
Cross talk between increased intracellular zinc (Zn2+) and accumulation of reactive oxygen species in chemical ischemia
Both zinc (Zn2+) and reactive oxygen species (ROS) have been shown to accumulate during hypoxic-ischemic stress and play important roles in pathological processes. To understand the cross talk between the two of them, here we studied Zn2+ and ROS accumulation by employing fluorescent probes in HeLa cells to further the understanding of the cause and effect relationship of these two important cellular signaling systems during chemical-ischemia, stimulated by oxygen and glucose deprivation (OGD). We observed two Zn2+ rises that were divided into four phases in the course of 30 min of OGD. The first Zn2+ rise was a transient,...
Source: AJP: Cell Physiology - October 9, 2017 Category: Cytology Authors: Slepchenko, K. G., Lu, Q., Li, Y. V. Tags: RESEARCH ARTICLE Source Type: research
Reciprocal regulation of miR-214 and PTEN by high glucose regulates renal glomerular mesangial and proximal tubular epithelial cell hypertrophy and matrix expansion
Aberrant expression of microRNAs (miRs) contributes to diabetic renal complications, including renal hypertrophy and matrix protein accumulation. Reduced expression of phosphatase and tensin homolog (PTEN) by hyperglycemia contributes to these processes. We considered involvement of miR in the downregulation of PTEN. In the renal cortex of type 1 diabetic mice, we detected increased expression of miR-214 in association with decreased levels of PTEN and enhanced Akt phosphorylation and fibronectin expression. Mesangial and proximal tubular epithelial cells exposed to high glucose showed augmented expression of miR-214. Muta...
Source: AJP: Cell Physiology - October 9, 2017 Category: Cytology Authors: Bera, A., Das, F., Ghosh-Choudhury, N., Mariappan, M. M., Kasinath, B. S., Ghosh Choudhury, G. Tags: RESEARCH ARTICLE Source Type: research
Comparative study of expression and activity of glucose transporters between stem cell-derived brain microvascular endothelial cells and hCMEC/D3 cells
In this study, we investigated the expression of glucose transporters and glucose diffusion across brain microvascular endothelial cells (BMECs) derived from healthy patient-derived induced pluripotent stem cells (iPSCs). We investigated the expression of different glucose transporters at the BBB using immunocytochemistry and flow cytometry and measured glucose uptake and diffusion across BMEC monolayers obtained from two iPSC lines and from hCMEC/D3 cells. BMEC monolayers showed expression of several glucose transporters, in particular GLUT1, GLUT3, and GLUT4. Diffusion of glucose across the monolayers was mediated via a ...
Source: AJP: Cell Physiology - October 9, 2017 Category: Cytology Authors: Al-Ahmad, A. J. Tags: RESEARCH ARTICLE Source Type: research
PEDF expression affects retinal endothelial cell proangiogenic properties through alterations in cell adhesive mechanisms
Pigment epithelium-derived factor (PEDF) is an endogenous inhibitor of angiogenesis. Although various ocular cell types including retinal endothelial cells (EC) produce PEDF, we know very little about cell autonomous effects of PEDF in these cell types. Here we determined how PEDF expression affects retinal EC proangiogenic properties. Retinal EC were prepared from wild-type (PEDF+/+) and PEDF-deficient (PEDF–/–) mice. The identity of EC was confirmed by staining for specific markers including vascular endothelial cadherin, CD31, and B4-lectin. Retinal EC also expressed VEGF receptor 1 and endoglin, as well as ...
Source: AJP: Cell Physiology - October 9, 2017 Category: Cytology Authors: Falero-Perez, J., Park, S., Sorenson, C. M., Sheibani, N. Tags: RESEARCH ARTICLE Source Type: research
A tale of two niches: differential functions for VCAM-1 in satellite cells under basal and injured conditions
Cell-cell adhesion molecules play key roles in maintaining quiescence or promoting activation of various stem cells in their niche. Muscle stem cells called satellite cells (SC) are critical for skeletal muscle regeneration after injury, but little is known about the role of adhesion molecules in regulating the behavior of these stem cells. Vascular cell adhesion molecule-1 (VCAM-1) is a cell-cell adhesion protein expressed on quiescent and activated SC whose function is unknown in this context. We deleted Vcam1 from SC using an inducible Cre recombinase in young mice. In the injured niche, Vcam1–/– SC underwen...
Source: AJP: Cell Physiology - October 1, 2017 Category: Cytology Authors: Choo, H.-J., Canner, J. P., Vest, K. E., Thompson, Z., Pavlath, G. K. Tags: RESEARCH ARTICLE Source Type: research
miR-4632 mediates PDGF-BB-induced proliferation and antiapoptosis of human pulmonary artery smooth muscle cells via targeting cJUN
MicroRNAs (miRNAs) can regulate the proliferative status of pulmonary artery smooth muscle cells (PASMCs), which is a core factor modulating pulmonary vascular remodeling diseases, such as atherosclerosis and pulmonary arterial hypertension (PAH). Our previous work has shown that miR-4632, a rarely reported miRNA, is significantly downregulated in platelet-derived growth factor (PDGF)-BB-stimulated human pulmonary artery smooth muscle cells (HPASMCs), yet its cell function and the underlying molecular mechanisms remain to be elucidated. Here, we find that miR-4632 is highly expressed in HPASMCs and its expression significa...
Source: AJP: Cell Physiology - October 1, 2017 Category: Cytology Authors: Qian, Z., Li, Y., Chen, J., Li, X., Gou, D. Tags: RESEARCH ARTICLE Source Type: research
Suppression of ciliary movements by a hypertonic stress in the newt olfactory receptor neuron
We examined the olfactory receptor neuron immersed in various extracellular media under the video-enhanced differential interference contrast microscope. The activation of voltage-gated Ca2+ channels by K+ depolarization or by application of Ca2+ to membrane-permeabilized olfactory cells did not affect the ciliary movement, suggesting that Ca2+ influx through the cell membrane has no direct effect on the movement. However, when an extracellular medium contained NaCl or sucrose at concentrations only 30% higher than normal levels, ciliary movement was greatly and reversibly suppressed. In contrast, a hypotonic solution of s...
Source: AJP: Cell Physiology - October 1, 2017 Category: Cytology Authors: Wakazono, Y., Sakurai, T., Terakawa, S. Tags: RESEARCH ARTICLE Source Type: research
Involvement of connexin 43 phosphorylation and gap junctional communication between smooth muscle cells in vasopressin-induced ROCK-dependent vasoconstriction after hemorrhagic shock
In conclusion, AVP-mediated vascular contractile effects are endothelium and myoendothelial gap junction independent. Gap junctions between VSMCs, gap junctional communication, and Cx43 phosphorylation at Ser262 play important roles in the vascular effects of AVP. RhoA/ROCK, but not PKC, is involved in this process. (Source: AJP: Cell Physiology)
Source: AJP: Cell Physiology - October 1, 2017 Category: Cytology Authors: Yang, G., Peng, X., Wu, Y., Li, T., Liu, L. Tags: RESEARCH ARTICLE Source Type: research
Understanding mechanisms and seeking cures for Alzheimer's disease: why we must be "extraordinarily diverse"
After more than a century since Dr. Alois Alzheimer first described the pathological hallmarks accompanying the defining clinical features of the disease, we have yet to deliver any meaningful disease-modifying treatments to our patients. In this article, I present a rationale for the need to be "extraordinarily diverse" in seeking effective ways to treat or prevent this devastating disease. This approach is based on applying a systems-biology perspective at the population level, using a diverse array of "OMICS" methodologies to identify molecular mechanisms associated with well-established AD risk factors including system...
Source: AJP: Cell Physiology - October 1, 2017 Category: Cytology Authors: Thambisetty, M. Tags: THEME Source Type: research
oxLDL induces endothelial cell proliferation via Rho/ROCK/Akt/p27kip1 signaling: opposite effects of oxLDL and cholesterol loading
Oxidized modifications of LDL (oxLDL) play a key role in the development of endothelial dysfunction and atherosclerosis. However, the underlying mechanisms of oxLDL-mediated cellular behavior are not completely understood. Here, we compared the effects of two major types of oxLDL, copper-oxidized LDL (Cu2+-oxLDL) and lipoxygenase-oxidized LDL (LPO-oxLDL), on proliferation of human aortic endothelial cells (HAECs). Cu2+-oxLDL enhanced HAECs’ proliferation in a dose- and degree of oxidation-dependent manner. Similarly, LPO-oxLDL also enhanced HAEC proliferation. Mechanistically, both Cu2+-oxLDL and LPO-oxLDL enhance HA...
Source: AJP: Cell Physiology - September 5, 2017 Category: Cytology Authors: Zhang, C., Adamos, C., Oh, M.-J., Baruah, J., Ayee, M. A. A., Mehta, D., Wary, K. K., Levitan, I. Tags: RESEARCH ARTICLE Source Type: research
Characterization of muscle ankyrin repeat proteins in human skeletal muscle
Muscle ankyrin repeat proteins (MARPs) are a family of titin-associated, stress-response molecules and putative transducers of stretch-induced signaling in skeletal muscle. In cardiac muscle, cardiac ankyrin repeat protein (CARP) and diabetes-related ankyrin repeat protein (DARP) reportedly redistribute from binding sites on titin to the nucleus following a prolonged stretch. However, it is unclear whether ankyrin repeat domain protein 2 (Ankrd 2) shows comparable stretch-induced redistribution to the nucleus. We measured the following in rested human skeletal muscle: 1) the absolute amount of MARPs and 2) the distribution...
Source: AJP: Cell Physiology - September 5, 2017 Category: Cytology Authors: Wette, S. G., Smith, H. K., Lamb, G. D., Murphy, R. M. Tags: RESEARCH ARTICLE Source Type: research
Mechanism of action of the anti-inflammatory connexin43 mimetic peptide JM2
Connexin-based therapeutics have shown the potential for therapeutic efficacy in improving wound healing. Our previous work demonstrated that the connexin43 (Cx43) mimetic peptide juxtamembrane 2 (JM2) reduced the acute inflammatory response to a submuscular implant model by inhibiting purinergic signaling. Given the prospective application in improving tissue-engineered construct tolerance that these results indicated, we sought to determine the mechanism of action for JM2 in the present study. Using confocal microscopy, a gap-FRAP cell communication assay, and an ethidium bromide uptake assay of hemichannel function we f...
Source: AJP: Cell Physiology - September 5, 2017 Category: Cytology Authors: Rhett, J. M., Calder, B. W., Fann, S. A., Bainbridge, H., Gourdie, R. G., Yost, M. J. Tags: RESEARCH ARTICLE Source Type: research
Lipopolysaccharide downregulates macrophage-derived IL-22 to modulate alcohol-induced hepatocyte cell death
Interleukin-22 (IL-22) is a Th17 cell hepatoprotective cytokine that is undergoing clinical trials to treat patients with alcoholic hepatitis (AH). Lipopolysaccharide (LPS) activation of macrophage is implicated in hepatocyte cell death and pathogenesis of AH. The role of IL-22 production from macrophage, its regulation by LPS, and effects on alcohol-induced hepatocyte cell death are unexplored and were examined in this study. Low levels of IL-22 mRNA/protein were detected in macrophage but were significantly upregulated by 6.5-fold in response to the tissue reparative cytokine IL-10. Conversely, LPS significantly decrease...
Source: AJP: Cell Physiology - September 5, 2017 Category: Cytology Authors: Liu, Y., Verma, V. K., Malhi, H., Gores, G. J., Kamath, P. S., Sanyal, A., Chalasani, N., Gao, B., Shah, V. H. Tags: RESEARCH ARTICLE Source Type: research
Reduced SCD1 activity alters markers of fatty acid reesterification, glyceroneogenesis, and lipolysis in murine white adipose tissue and 3T3-L1 adipocytes
White adipose tissue (WAT) has a critical role in lipid handling. Previous work demonstrated that SCD1 is an important regulator of WAT fatty acid (FA) composition; however, its influence on the various interconnected pathways influencing WAT lipid handling remains unclear. Our objective was to investigate the role of SCD1 on WAT lipid handling using Scd1 knockout (KO) mice and SCD1-inhibited 3T3-L1 adipocytes by measuring gene, protein, and metabolite markers related to FA reesterification, glyceroneogenesis, and lipolysis. Triacylglycerol (TAG) content was higher in inguinal WAT (iWAT) from KO mice compared with wild-typ...
Source: AJP: Cell Physiology - September 1, 2017 Category: Cytology Authors: Dragos, S. M., Bergeron, K. F., Desmarais, F., Suitor, K., Wright, D. C., Mounier, C., Mutch, D. M. Tags: RESEARCH ARTICLE Source Type: research
