Journals American Journal of Physiology...

American Journal of Physiology. Cell Physiology
Ann-Sofie Schreurs, Samantha Torres, Tiffany Truong, Eric L Moyer, Akhilesh Kumar, Candice G T Tahimic, Joshua S Alwood, Ruth K Globus
Accumulation of oxidative damage from excess reactive oxygen species (ROS) may contribute to skeletal aging and mediate adverse responses to physiological challenges. Wildtype (WT) and transgenic mice (male, 16 weeks of age) with human catalase targeted to the mitochondria (mCAT) were analyzed for skeletal responses to the remodeling stimuli of combined hindlimb unloading and exposure to ionizing radiation (137Cs , 2 Gy). Treatment for 2wk caused lipid peroxidation in WT bones but not mCAT, showing that transgene expression mitigated oxidative stress...
August 12, 2020: American Journal of Physiology. Cell Physiology
Irene S Tobias, Andrew J Galpin
Human skeletal muscle is a heterogeneous tissue composed of multiple fiber types that express unique contractile and metabolic properties. While analysis of mixed fiber samples predominates and holds value, increasing attention has been directed towards studying proteins segregated by fiber type, a methodological distinction termed "fiber type-specific." Fiber type-specific protein studies have the advantage of uncovering key molecular effects that are often missed in mixed fiber homogenate studies but also require greater time and resource-intensive methods, particularly when applied to human muscle...
August 12, 2020: American Journal of Physiology. Cell Physiology
Kalpaj R Parekh, Janna Nawroth, Albert Pai, Shana M Busch, Christiana N Senger, Amy L Ryan
Summary/Abstract The ability to replace defective cells in an airway with cells that can engraft, integrate and restore a functional epithelium could potentially cure a number of lung diseases. Progress toward the development of strategies to regenerate the adult lung by either in vivo or ex vivo targeting of endogenous stem cells or pluripotent stem cell derivatives, is limited by our fundamental lack of understanding of the mechanisms controlling human lung development, the precise identity and function of human lung stem and progenitor cell types, and the genetic and epigenetic control of human lung fate...
August 12, 2020: American Journal of Physiology. Cell Physiology
Chun K Kim, Toni R Pak
miRNAs are short, noncoding RNAs that are evolutionarily conserved across many different species. miRNA regulation of gene expression, specifically in the context of the mammalian brain, has been well characterized; however, the regulation of miRNA degradation is still the focus of ongoing research. This review will focus on recent findings concerning the cellular mechanisms that govern miRNA degradation with an emphasis on TDMD (target mediated miRNA degradation) and how this phenomenon is uniquely poised to maintain homeostasis in neuronal systems...
August 12, 2020: American Journal of Physiology. Cell Physiology
Natalie C Fredette, Eliyah Malik, Marah L Mukhtar, Eric R Prossnitz, Naohiro Terada
Hypertension (HTN) is a polyfactorial disease that can manifest severe cardiovascular pathologies such as heart failure or stroke. Genome Wide Association Studies (GWAS) of HTN indicate that single nucleotide polymorphisms (SNPs) contribute to increased risk for HTN and resistance to some HTN drug regimens (19, 26, 35, 52). However, cellular mechanistic insights of such SNPs remain largely unknown. Using a HTN patient-derived induced pluripotent stem cell (iPSC) bank and CRISPR/Cas9-mediated gene editing approach, we investigated the effects of a female HTN risk-associated SNP (rs1154431) of the G protein-coupled estrogen receptor (GPER) (5) in vascular endothelial cells...
August 12, 2020: American Journal of Physiology. Cell Physiology
Rongyi Shi, Yiyi Wang, Ya Gao, Xiaoli Xu, Shuyu Mao, Yue Xiao, Shuang Song, Liangyan Wang, Bing Tian, Ye Zhao, Yuejin Hua, Hong Xu
Human flap endonuclease 1 (FEN1) is a structure-specific, multi-functional endonuclease essential for DNA replication and repair. Our previous study showed that in response to DNA damage, FEN1 interacts with the PCNA-like Rad9-Rad1-Hus1 complex instead of PCNA to engage in DNA repair activities, such as stalled DNA replication fork repair, and undergoes SUMOylation by SUMO-1. Here, we report that succinylation of FEN1 was stimulated in response to DNA replication fork-stalling agents, such as UV irradiation, hydroxyurea, camptothecin, and mitomycin C...
August 12, 2020: American Journal of Physiology. Cell Physiology
Masood Sepehrimanesh, Baojin Ding
Generation of neurons from human induced pluripotent stem cells (hiPSCs) overcomes the limited access to human brain samples and greatly facilitates the progress of research in neurological diseases. However, it is still a challenge to generate a particular neuronal subtype with high purity and yield for determining the pathogenesis of diseased neurons using biochemical approaches. Motor neurons (MNs) are a specialized neuronal subtype responsible for governing both autonomic and volitional movement. Dysfunctions in MNs are implicated in a variety of movement diseases, such as amyotrophic lateral sclerosis (ALS)...
August 12, 2020: American Journal of Physiology. Cell Physiology
Peyton E VanWinkle, Felicia Parish, Yvonne J K Edwards, Elizabeth Sztul
The endoplasmic reticulum protein Jagunal (JAGN1) was first identified as a requirement for Drosophila melanogaster oocyte development. Subsequent studies in human patients linked mutations in JAGN1 to Severe Congenital Neutropenia (SCN), as well as a broad range of additional symptoms, suggesting that JAGN1 function is required in many tissues. Moreover, JAGN1 orthologues are found throughout animal and plant phylogeny, suggesting that JAGN1 supports fundamental cellular processes not restricted to egg development or neutrophil function...
August 12, 2020: American Journal of Physiology. Cell Physiology
David C Hughes, Leslie M Baehr, Julia R Driscoll, Sarah A Lynch, David S Waddell, Sue C Bodine
Muscle-specific E3 ubiquitin ligases have been identified in muscle atrophy-inducing conditions. The purpose of the current study was to explore the functional role of Fbxl22, and a newly identified splice variant (Fbxl22-193), in skeletal muscle homeostasis and neurogenic muscle atrophy. In mouse C2 C12 muscle cells, promoter fragments of the Fbxl22 gene were cloned and fused with the secreted alkaline phosphatase reporter gene to assess the transcriptional regulation of Fbxl22. The tibialis anterior muscles of male C57/BL6 mice (12-16 weeks old) were electroporated with expression plasmids containing the cDNA of two Fbxl22 splice variants and tissues collected after 7, 14 and 28 days...
August 12, 2020: 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
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