Autophagy in chronic liver diseases: the two faces of Janus
Alcoholic liver disease (ALD) and nonalcoholic fatty liver disease (NAFLD) are the leading causes of cirrhosis and increase the risk of hepatocellular carcinoma and liver-related death. ALD and NAFLD share common pathogenic features extending from isolated steatosis to steatohepatitis and steatofibrosis, which can progress to cirrhosis and hepatocellular carcinoma. The pathophysiological mechanisms of the progression of NAFLD and ALD are complex and still unclear. Important links between the regulation of autophagy (macroautophagy and chaperone-mediated autophagy) and chronic liver diseases have been reported. Autophagy ma...
Source: AJP: Cell Physiology - March 2, 2017 Category: Cytology Authors: Gual, P., Gilgenkrantz, H., Lotersztajn, S. Tags: REVIEW Source Type: research
Nitric oxide: whats new to NO?
Nitric oxide (NO) is one of the critical components of the vasculature, regulating key signaling pathways in health. In macrovessels, NO functions to suppress cell inflammation as well as adhesion. In this way, it inhibits thrombosis and promotes blood flow. It also functions to limit vessel constriction and vessel wall remodeling. In microvessels and particularly capillaries, NO, along with growth factors, is important in promoting new vessel formation, a process termed angiogenesis. With age and cardiovascular disease, animal and human studies confirm that NO is dysregulated at multiple levels including decreased product...
Source: AJP: Cell Physiology - March 2, 2017 Category: Cytology Authors: Ghimire, K., Altmann, H. M., Straub, A. C., Isenberg, J. S. Tags: THEME Source Type: research
C-reactive protein isoforms differentially affect outer blood-retinal barrier integrity and function
In conclusion, the presence of mCRP within retinal tissue may lead to disruption of the oBRB, an effect that may be modified in the presence of corticosteroids or anti-VEGF drugs. (Source: AJP: Cell Physiology)
Source: AJP: Cell Physiology - February 28, 2017 Category: Cytology Authors: Molins, B., Pascual, A., Mendez, , Llorenc, V., Zarranz-Ventura, J., Mesquida, M., Adan, A., Martorell, J. Tags: RESEARCH ARTICLE Source Type: research
Prenatal myonuclei play a crucial role in skeletal muscle hypertrophy in rodents
Multinucleated muscle fibers are formed by the fusion of myogenic progenitor cells during embryonic and fetal myogenesis. However, the role of prenatally incorporated myonuclei in the skeletal muscle fibers of adult animals is poorly understood. We demonstrated, using muscle-specific reporter mice, that the prenatal myonuclei remained in the adult soleus muscle, although cardiotoxin injection caused the loss of prenatal myonuclei. Overloading by the tendon transection of synergists failed to induce compensatory hypertrophy in regenerated soleus muscle fibers of adult rats, whereas unloading by tail suspension normally indu...
Source: AJP: Cell Physiology - February 28, 2017 Category: Cytology Authors: Kawano, F., Ono, Y., Fujita, R., Watanabe, A., Masuzawa, R., Shibata, K., Hasegawa, S., Nakata, K., Nakai, N. Tags: RESEARCH ARTICLE Source Type: research
Src-independent ERK signaling through the rat {alpha}3 isoform of Na/K-ATPase
The Na/K-ATPase α1 polypeptide supports both ion-pumping and signaling functions. The Na/K-ATPase α3 polypeptide differs from α1 in both its primary structure and its tissue distribution. The expression of α3 seems particularly important in neurons, and recent clinical evidence supports a unique role of this isoform in normal brain function. The nature of this specific role of α3 has remained elusive, because the ubiquitous presence of α1 has hindered efforts to characterize α3-specific functions in mammalian cell systems. Using Na/K-ATPase α1 knockdown pig kidney cells (PY-1...
Source: AJP: Cell Physiology - February 28, 2017 Category: Cytology Authors: Madan, N., Xu, Y., Duan, Q., Banerjee, M., Larre, I., Pierre, S. V., Xie, Z. Tags: RESEARCH ARTICLE Source Type: research
Muscle-specific microRNA-206 targets multiple components in dystrophic skeletal muscle representing beneficial adaptations
Over the last several years, converging lines of evidence have indicated that miR-206 plays a pivotal role in promoting muscle differentiation and regeneration, thereby potentially impacting positively on the progression of neuromuscular disorders, including Duchenne muscular dystrophy (DMD). Despite several studies showing the regulatory function of miR-206 on target mRNAs in skeletal muscle cells, the effects of overexpression of miR-206 in dystrophic muscles remain to be established. Here, we found that miR-206 overexpression in mdx mouse muscles simultaneously targets multiple mRNAs and proteins implicated in satellite...
Source: AJP: Cell Physiology - February 28, 2017 Category: Cytology Authors: Amirouche, A., Jahnke, V. E., Lunde, J. A., Koulmann, N., Freyssenet, D. G., Jasmin, B. J. Tags: RESEARCH ARTICLE Source Type: research
Canstatin stimulates migration of rat cardiac fibroblasts via secretion of matrix metalloproteinase-2
In conclusion, this study revealed a novel function of canstatin for inducing cell migration of adult rat cardiac fibroblasts at least in part by ERK phosphorylation through MMP-2 secretion, possibly via actin cytoskeletal change. (Source: AJP: Cell Physiology)
Source: AJP: Cell Physiology - February 28, 2017 Category: Cytology Authors: Okada, M., Murata, N., Yamawaki, H. Tags: RESEARCH ARTICLE Source Type: research
Changes in mitochondrial morphology and organization can enhance energy supply from mitochondrial oxidative phosphorylation in diabetic cardiomyopathy
Diabetic cardiomyopathy is accompanied by metabolic and ultrastructural alterations, but the impact of the structural changes on metabolism itself is yet to be determined. Morphometric analysis of mitochondrial shape and spatial organization within transverse sections of cardiomyocytes from control and streptozotocin-induced type I diabetic Sprague-Dawley rats revealed that mitochondria are 20% smaller in size while their spatial density increases by 53% in diabetic cells relative to control myocytes. Diabetic cells formed larger clusters of mitochondria (60% more mitochondria per cluster) and the effective surface-to-volu...
Source: AJP: Cell Physiology - February 7, 2017 Category: Cytology Authors: Jarosz, J., Ghosh, S., Delbridge, L. M. D., Petzer, A., Hickey, A. J. R., Crampin, E. J., Hanssen, E., Rajagopal, V. Tags: RAPID REPORT Source Type: research
Aspirin therapy reduces the ability of platelets to promote colon and pancreatic cancer cell proliferation: Implications for the oncoprotein c-MYC
In conclusion, we show for the first time that inhibition of platelets by aspirin can affect their ability to induce cancer cell proliferation through the modulation of the c-MYC oncoprotein. (Source: AJP: Cell Physiology)
Source: AJP: Cell Physiology - February 7, 2017 Category: Cytology Authors: Mitrugno, A., Sylman, J. L., Ngo, A. T. P., Pang, J., Sears, R. C., Williams, C. D., McCarty, O. J. T. Tags: RESEARCH ARTICLE Source Type: research
The plasma membrane metal-ion transporter ZIP14 contributes to nontransferrin-bound iron uptake by human {beta}-cells
The relationship between iron and β-cell dysfunction has long been recognized as individuals with iron overload display an increased incidence of diabetes. This link is usually attributed to the accumulation of excess iron in β-cells leading to cellular damage and impaired function. Yet, the molecular mechanism(s) by which human β-cells take up iron has not been determined. In the present study, we assessed the contribution of the metal-ion transporters ZRT/IRT-like protein 14 and 8 (ZIP14 and ZIP8) and divalent metal-ion transporter-1 (DMT1) to iron uptake by human β-cells. Iron was provided to the cel...
Source: AJP: Cell Physiology - February 7, 2017 Category: Cytology Authors: Coffey, R., Knutson, M. D. Tags: RESEARCH ARTICLE Source Type: research
Renin-angiotensin-aldosterone system inhibitors improve membrane stability and change gene-expression profiles in dystrophic skeletal muscles
Angiotensin-converting enzyme inhibitors (ACEi) and mineralocorticoid receptor (MR) antagonists are FDA-approved drugs that inhibit the renin-angiotensin-aldosterone system (RAAS) and are used to treat heart failure. Combined treatment with the ACEi lisinopril and the nonspecific MR antagonist spironolactone surprisingly improves skeletal muscle, in addition to heart function and pathology in a Duchenne muscular dystrophy (DMD) mouse model. We recently demonstrated that MR is present in all limb and respiratory muscles and functions as a steroid hormone receptor in differentiated normal human skeletal muscle fibers. The go...
Source: AJP: Cell Physiology - February 7, 2017 Category: Cytology Authors: Chadwick, J. A., Bhattacharya, S., Lowe, J., Weisleder, N., Rafael-Fortney, J. A. Tags: RESEARCH ARTICLE Source Type: research
Threshold levels of extracellular L-arginine that trigger NOS-mediated ROS/RNS production in cardiac ventricular myocytes
In this study we aimed to determine the levels of external L-Arg that trigger ROS/RNS production in cardiac myocytes. To this goal, we used a two-step experimental design in which acutely isolated cardiomyocytes were loaded with the dye coelenterazine that greatly increases its fluorescence quantum yield in the presence of ONOO– and O2–. Cells were then exposed to different concentrations of extracellular L-Arg and changes in fluorescence were followed spectrofluorometrically. It was found that below a threshold value of ~100 µM, decreasing concentrations of L-Arg progressively increased ONOO–/ O2&n...
Source: AJP: Cell Physiology - February 7, 2017 Category: Cytology Authors: Ramachandran, J., Peluffo, R. D. Tags: RESEARCH ARTICLE Source Type: research
Three distinct cell populations express extracellular matrix proteins and increase in number during skeletal muscle fibrosis
Tissue extracellular matrix (ECM) provides structural support and creates unique environments for resident cells (Bateman JF, Boot-Handford RP, Lamandé SR. Nat Rev Genet 10: 173–183, 2009; Kjaer M. Physiol Rev 84: 649–98, 2004). However, the identities of cells responsible for creating specific ECM components have not been determined. In striated muscle, the identity of these cells becomes important in disease when ECM changes result in fibrosis and subsequent increased tissue stiffness and dysfunction. Here we describe a novel approach to isolate and identify cells that maintain the ECM in both healthy ...
Source: AJP: Cell Physiology - February 7, 2017 Category: Cytology Authors: Chapman, M. A., Mukund, K., Subramaniam, S., Brenner, D., Lieber, R. L. Tags: RESEARCH ARTICLE Source Type: research
MicroRNA-125a-5p alleviates the deleterious effects of ox-LDL on multiple functions of human brain microvessel endothelial cells
In conclusion, miR-125a-5p could counteract the effects of ox-LDL on various HBMEC functions via regulating the EGFR/ERK/p38 MAPK and PI3K/Akt/eNOS pathways and cleaved caspase-3, ICAM-1, and VCAM-1 expression. (Source: AJP: Cell Physiology)
Source: AJP: Cell Physiology - February 7, 2017 Category: Cytology Authors: Pan, Q., Liao, X., Liu, H., Wang, Y., Chen, Y., Zhao, B., Lazartigues, E., Yang, Y., Ma, X. Tags: RESEARCH ARTICLE Source Type: research
The Drosophila indirect flight muscle myosin heavy chain isoform is insufficient to transform the jump muscle into a highly stretch-activated muscle type
Stretch activation (SA) is a delayed increase in force that enables high power and efficiency from a cyclically contracting muscle. SA exists in various degrees in almost all muscle types. In Drosophila, the indirect flight muscle (IFM) displays exceptionally high SA force production (FSA), whereas the jump muscle produces only minimal FSA. We previously found that expressing an embryonic (EMB) myosin heavy chain (MHC) isoform in the jump muscle transforms it into a moderately SA muscle type and enables positive cyclical power generation. To investigate whether variation in MHC isoforms is sufficient to produce even higher...
Source: AJP: Cell Physiology - January 31, 2017 Category: Cytology Authors: Zhao, C., Swank, D. M. Tags: RESEARCH ARTICLE Source Type: research
