Journals American Journal of Physiology...

American Journal of Physiology. Cell Physiology
Sophie I Hamstra, Kennedy C Whitley, Ryan W Baranowski, Nigel Kurgan, Jessica L Braun, Holt N Messner, Val A Fajardo
Cardiac contractile function is largely mediated by the regulation of Ca2+ cycling throughout the lifespan. The sarco(endo)plasmic reticulum Ca2+ ATPase (SERCA) pump is paramount to cardiac Ca2+ regulation, and it is well established that SERCA dysfunction pathologically contributes to cardiomyopathy and heart failure. Phospholamban (PLN) is a well-known inhibitor of the SERCA pump and its regulation of SERCA2a - the predominant cardiac SERCA isoform - contributes significantly to proper cardiac function. Glycogen synthase kinase 3 (GSK3) is a serine/threonine kinase involved in several metabolic pathways and we and others have shown that it regulates SERCA function...
August 5, 2020: American Journal of Physiology. Cell Physiology
Songtao Shi, Hongli Li
Interstitial lung disease (ILD) comprises of a group of diffuse parenchymal lung disorders that are strongly associated with substantial morbidity and mortality. Previous studies have highlighted the therapeutic significance of microRNAs (miRNAs) in the treatment of ILD. Thus, this study aims to investigate the mechanism by which miR-140 affects ILD through the regulation of osteoglycin (OGN)-Wnt signaling pathway. Gene expression microarray analysis was performed to screen ILD-related differentially expressed genes and miRNAs that regulated OGN...
August 5, 2020: American Journal of Physiology. Cell Physiology
An-Ci Siao, Yen-Yue Lin, Li-Jane Shih, Yi-Wei Tsuei, Chih-Pin Chuu, Yow-Chii Kuo, Yung-Hsi Kao
Endothelin (ET)-1 regulates adipogenesis and the endocrine activity of fat cells. However, relatively little is known about the ET-1 signaling pathway in preadipocyte growth. We used 3T3-L1 preadipocytes to investigate the signaling pathways involved in ET-1 modulation of preadipocyte proliferation. As indicated by an increased number of cells and greater incorporation of BrdU, the stimulation of preadipocyte growth by ET-1 depends on concentration and timing. The concentration of ET-1 that increased preadipocyte number by 50-70% was approximately 100 nM for approximately 24-48 h of treatment...
August 5, 2020: American Journal of Physiology. Cell Physiology
Bei Chen, Hongen Xu, Yanfang Mi, Wei Jiang, Dan Guo, Jinhui Zhang, Yulin Zhao, Wenxue Tang
Mutations in Connexin 30 (Cx30) are known to cause severe congenital hearing impairment; however, the mechanism by which Cx30 mediates homeostasis of endocochlear gap junctions is unclear. We used a gene deletion mouse model to explore the mechanisms of Cx30 in preventing hearing loss. Our results suggest that despite severe loss of the auditory brain response and endocochlear potential at postnatal day 18, Cx30-/- mice only show sporadic loss of the outer hair cells. This inconsistency in the time course and severity of hearing and hair cell losses in Cx30-/- mice might be explained in part by an increase in reactive oxygen species generation beginning at postnatal day 10...
August 5, 2020: American Journal of Physiology. Cell Physiology
Emma Teal, Martha Dua-Awereh, Sabrina T Hirshorn, Yana Zavros
Spasmolytic polypeptide/TFF2-expressing metaplasia is a mucous-secreting reparative lineage that emerges at the ulcer margin after in response to gastric injury. Under conditions of chronic inflammation with parietal cell loss, SPEM has been found to emerge and evolve into neoplasia. Cluster-of-differentiation gene 44 (CD44) is known to coordinate normal and metaplastic epithelial cell proliferation. In particular, CD44 variant isoform 9 (CD44v9) associates with the cysteine-glutamate transporter xCT, stabilizes the protein and provides defense against reactive oxygen species (ROS)...
August 5, 2020: American Journal of Physiology. Cell Physiology
Xu Cao, Manoocher Soleimani, Bret A Hughes
Anion channels in the retinal pigment epithelium (RPE) play an essential role in the transport of Cl- between the outer retina and the choroidal blood to regulate the ionic composition and volume of the subretinal fluid that surrounds the photoreceptor outer segments. Recently, we reported that the anion conductance of the mouse RPE basolateral membrane is highly selective for the biologically-active anion thiocyanate (SCN- ), a property that does not correspond with any of the Cl- channels that have been found to be expressed in the RPE to date...
July 29, 2020: American Journal of Physiology. Cell Physiology
Dong-Dong Gao, Long-Long Wang, Jia-Wen Xu, Zhuo-Er Qiu, Yun-Xin Zhu, Yi-Lin Zhang, Wen-Liang Zhou
The neurohypophyseal hormone oxytocin (OT) plays critical roles in lactation and parturition, whilst its function in male reproduction system is largely unknown. This study aims to investigate the effect of OT on regulating transepithelial ion transport in rat cauda epididymal epithelium. Using RT-PCR, western blot and immunohistochemical analysis, we found that OT receptor (OTR) was expressed and localized at the basal membrane of rat cauda epididymal epithelium. The short-circuit current (ISC ) measurement showed that basolateral application of OT to the primary cultured rat cauda epididymal epithelial cells elicited an increase in ISC , which was abrogated by pretreating the epithelial cells with CFTRinh -172, a blocker of cystic fibrosis transmembrane conductance regulator (CFTR)...
July 29, 2020: American Journal of Physiology. Cell Physiology
Emma J O'Connell, Chloe-Anne Martinez, Yichuan G Liang, Peter A Cistulli, Kristina M Cook
Humans have internal circadian clocks that ensure important physiological functions occur at specific times of the day. These molecular clocks are regulated at the genomic level and exist in most cells of the body. Multiple circadian resetting cues have been identified, including light, temperature and food. Recently, oxygen has been identified as a resetting cue and emerging science indicates that this occurs through interactions at the cellular level between the circadian transcription-translation feedback loop and the hypoxia inducible pathway (HIF; subject of the 2019 Nobel Prize in Physiology or Medicine)...
July 29, 2020: American Journal of Physiology. Cell Physiology
Sidney Abou Sawan, Michael Mazzulla, Daniel R Moore, Nathan Hodson
Skeletal muscle is a highly plastic tissue capable of remodeling in response to a range of physiological stimuli including nutrients and exercise. Historically, the lysosome has been considered an essentially catabolic organelle contributing to autophagy, phagocytosis, and exo/endocytosis in skeletal muscle. However, recent evidence has emerged of several anabolic roles for the lysosome including the requirement for autophagy in skeletal muscle mass maintenance, the discovery of the lysosome as an intracellular signaling hub for mTORC1 activation, and the importance of TFEB/lysosomal biogenesis-related signaling in the regulation of mTORC1-mediated protein synthesis...
July 29, 2020: American Journal of Physiology. Cell Physiology
Jong Hoon Choi, Lorena Loarca, Jose M De Hoyos-Vega, Neda Dadgar, Kevin Loutherback, Vijay H Shah, Gulnaz Stybayeva, Alexander Revzin
A number of cell culture approaches have been described for maintenance of primary hepatocytes. Forming hepatocytes into 3D spheroids is one well accepted method for extending epithelial phenotype of these cells. Our lab has previously observed enhanced function of 2D (monolayer) hepatocyte cultures in microfluidic devices due to increased production of several hepato-inductive growth factors, including hepatocyte growth factor (HGF). In the present study we wanted to test a hypothesis that placing hepatocytes spheroids (3D) into microfluidic devices will also result in enhanced phenotype and function...
July 22, 2020: American Journal of Physiology. Cell Physiology
Hygor N Araujo, Tanes I Lima, Dimitrius Santiago P S F Guimarães, Andre G Oliveira, Bianca C Favero-Santos, Renato C S Branco, Rafaela Mariano da Silva Araújo, Alvaro F B Dantas, Alex Castro, Mara Patrícia T Chacon-Mikahill, Elaine Minatel, Murilo V Geraldo, Everardo Magalhães Carneiro, Alice C Rodrigues, Vihang A Narkar, Leonardo R Silveira
Lin28a/miRNA let-7b-5p pathway has emerged as a key regulators of energy homeostasis in the skeletal muscle. However, the mechanism through which this pathway is regulated in the skeletal muscle has remained unclear. We have found that eight weeks of aerobic training (Tr) markedly decreased let-7b-5p expression in murine skeletal muscle, whereas high-fat diet (Hfd) decreased it's expression. Conversely, Lin28a expression, a well-known inhibitor of let-7b-5p, was induced by Tr and decreased by Hfd. Similarly, in human muscle biopsies, Tr increased LIN28 expression and decreased let-7b-5p expression...
July 22, 2020: American Journal of Physiology. Cell Physiology
Prasenjit Mitra
Severe acute respiratory syndrome coronavirus (SARS-CoV), an enveloped virus with a positive-sense single-stranded RNA genome facilitates the host cell entry through intricate interactions with proteins and lipids of the cell membrane. The detailed molecular mechanism involves binding to the host cell receptor and fusion at the plasma membrane or after being trafficked to late endosomes under favorable environmental conditions. A crucial event in the process is the proteolytic cleavage of the viral spike protein by the host's endogenous proteases that releases the fusion peptide enabling fusion with the host cellular membrane system...
July 20, 2020: American Journal of Physiology. Cell Physiology
Kirk L Hamilton
No abstract text is available yet for this article.
July 15, 2020: American Journal of Physiology. Cell Physiology
Tani Leigh, Rosario G Scalia, Michael V Autieri
The inflammatory response is a complex, tightly regulated process activated by tissue wounding, foreign body invasion, and sterile inflammation. Over the decades, great progress has been made to advance our understanding of this process. One often overlooked aspect of inflammation is its sequel; resolution. We know that dysregulated resolution often results in numerous chronic degenerative diseases such as arthritis, cancer, and asthma. However, identification of components and mechanisms of resolving pathways lag behind those of pro-inflammatory processes, yet represent overlooked therapeutic opportunities...
July 15, 2020: American Journal of Physiology. Cell Physiology
Alan A Hopkins, Rory Murphy, Mustapha Irnaten, Deborah M Wallace, Barry Quill, Colm 'Brien
The primary biomechanical driver of pathological glaucomatous cupping remains unknown. Finite element modelling indicates that stress and strain play key roles. Primarily a review article we utilise known biomechanical data and currently unpublished results from our lab to propose a 3 stage, tissue stiffness-based model to explain glaucomatous cupping occurring at variable levels of translaminar pressure (TLP). In stage 1, a short-term increase in TLP gradient induces a transient increase in LC strain. Beyond a critical level of strain, the tissue stiffness rises steeply provoking cellular responses via integrin mediated mechanotransduction...
July 15, 2020: American Journal of Physiology. Cell Physiology
Liqun Sun, Meihua Sun, Ke Ma, Jiangtao Liu
Necrotizing enterocolitis (NEC) is an acute intestinal condition accounting for severe mortality and morbidity in preterm infants. This study aimed to identify the possible roles of let-7d-5p in neonatal rats with NEC. The differentially expressed genes (DEGs) related to NEC were initially screened in silico. After establishment of NEC rat models, the measurement of the expression of let-7d-5p, galectin-3 (LGALS3), toll-like receptor 4 (TLR4) and nuclear factor kappa B (NF-κB) as well as proinflammatory cytokines (TNF-α, IL-1b and IL-6) was conducted...
July 15, 2020: American Journal of Physiology. Cell Physiology
János G Filep, Amiram Ariel
Neutrophils are polymorphonuclear leukocytes that play a central role in host defense against infection and tissue injury. They are rapidly recruited to the inflamed site and execute a variety of functions to clear invading pathogens and damaged cells. However, many of their defense mechanisms are capable of inflicting collateral tissue damage. Neutrophil-driven inflammation is a unifying mechanism underlying many common diseases. Efficient removal of neutrophils from inflammatory loci is critical for timely resolution of inflammation and return to homeostasis...
July 15, 2020: American Journal of Physiology. Cell Physiology
Douglas W Van Pelt, Ivan J Vechetti, Marcus M Lawrence, Kathryn L Van Pelt, Parth Patel, Benjamin F Miller, Timothy A Butterfield, Esther E Dupont-Versteegden
Small non-coding microRNAs (miRNAs) are important regulators of skeletal muscle size and circulating miRNAs within extracellular vesicles (EVs) may contribute to atrophy and its associated systemic effects. The purpose of this study was to understand how muscle atrophy and regrowth alters in vivo serum EV miRNA content. We also associated changes in serum EV miRNA with protein synthesis, protein degradation and miRNA within muscle, kidney and liver. We subjected adult (10 mo.) F334/BN rats to 3 conditions: weight-bearing (WB), hindlimb suspension (HS) for 7 days to induce muscle atrophy, and HS for 7 days followed by 7 days of reloading (HSR)...
July 8, 2020: American Journal of Physiology. Cell Physiology
Chang Song, Qiang Yue, Auriel Moseley, Otor Al-Khalili, Brandi M Wynne, Heping Ma, Lihua Wang, Douglas C Eaton
ENaC gating is regulated by phosphatidylinositol 4,5-bisphosphate (PIP2 ). The PIP2 -dependent regulation of ENaC is mediated by the myristoylated alanine-rich protein kinase C substrate-like protein-1 (MLP-1). MLP-1 binds to PIP2 at the plasma membrane. We examined MLP-1 regulation of ENaC in DCT-15 cells. MLP-1 consists of a positively charged effector domain that sequesters PIP2 and contains serines that are a PKC targets and controls MLP-1 membrane association; a myristoylation domain promoting membrane association, and a multiple homology 2 domain of unknown function...
July 8, 2020: American Journal of Physiology. Cell Physiology
Chiara Scognamiglio, Alessandro Soloperto, Giancarlo Ruocco, Gianluca Cidonio
Bioprinting aims to direct the spatial arrangement in three dimensions of cells, biomaterials and growth factors. The biofabrication of clinically relevant constructs for the repair or modelling of either diseased or damaged tissues is rapidly advancing, resulting in the ability to 3D print biomimetic platforms which imitate a large number of tissues in the human body. Primary tissue-specific cells are typically isolated from patients and used for the fabrication of 3D models for drug screening or tissue repair purposes...
July 8, 2020: American Journal of Physiology. Cell Physiology
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