Journals American Journal of Physiology...

American Journal of Physiology. Cell Physiology
Yong Huang, Ke Ning, Wen-Wen Li, Ge Lin, Cui-Lan Hou, Ming-Jie Wang, Yi-Chun Zhu
Endogenous hydrogen sulfide (H2 S) affects cholesterol homeostasis and liver X receptor α (LXRα) expression. However, whether low density lipoprotein (LDL) receptor (LDLR), a key player in cholesterol homeostasis, is regulated by exogenous H2 S through LXRα signaling has not been determined. We investigated the effects of sodium hydrosulfide (NaHS, H2 S donor) on LDLR expression in the presence or absence of LXR agonists, T0901317 or GW3965 in HepG2 cells. We found that H2 S strongly accumulated LDLR precursor in the presence of T0901317...
September 16, 2020: American Journal of Physiology. Cell Physiology
Yuki Tamura, Karina Kouzaki, Takaya Kotani, Koichi Nakazato
The contraction of myotubes using electrical pulse stimulation is a research tool used to mimic muscle contractile activity and exercise in rodents and humans. Most protocols employed in previous work used low-frequency twitch contractions. However, high-frequency tetanus contractions that are more physiologically relevant to muscle contractions in vivo are poorly characterized. In this report, the similarities and differences in acute responses and chronic adaptations with different contractile modes using twitches (2 Hz, continuous, 3 h) and tetanus (66 Hz, on: 5 s/off: 5 s, 3 h) were investigated...
September 16, 2020: American Journal of Physiology. Cell Physiology
Varadarajan Sudhahar, Mustafa Nazir Okur, John P O'Bryan, Richard D Minshall, David Fulton, Masuko Ushio-Fukai, Tohru Fukai
Caveolin-1 (Cav-1) is a scaffolding protein and a major component of caveolae/lipid rafts. Previous reports have shown that endothelial dysfunction in Cav-1 deficient (Cav-1-/- ) mice is mediated by elevated oxidative stress through eNOS uncoupling and increased NADPH oxidase. Oxidant stress is the net balance of oxidant generation and scavenging and the role of Cav-1 as a regulator of antioxidant enzymes in vascular tissue is poorly understood. Extracellular SOD (SOD3) is a copper (Cu) containing enzyme that is secreted from vascular smooth muscle cells/fibroblasts and subsequently binds to the endothelial cells surface where it scavenges extracellular O2 - and preserves endothelial function...
September 16, 2020: American Journal of Physiology. Cell Physiology
Ning Wang, Xue-Feng Shi, Shakil A Khan, Benjamin Wang, Gregg L Semenza, Nanduri R Prabhakar, Jayasri Nanduri
The role of hypoxia-inducible factor (HIF)-1 in pancreatic β-cell response to intermittent hypoxia (IH) was examined. Studies were performed on adult wild type (WT), HIF-1α heterozygous (HET) as well as β-cell specific HIF-1-/- mice and mouse insulinoma (MIN6) cells exposed to IH patterned after blood O2 profiles during obstructive sleep apnea (OSA). WT mice treated with IH showed insulin resistance, and pancreatic β-cell dysfunction manifested as augmented basal insulin secretion, and impaired glucose stimulated insulin secretion (GSIS) and these effects were absent in HIF-1α HET mice...
September 16, 2020: American Journal of Physiology. Cell Physiology
Laura Carminati, Giulia Taraboletti
Thrombospondins (TSPs) are a family of five multimeric matricellular proteins. Through a wide range of interactions, TSPs play pleiotropic roles in embryogenesis and in tissue remodeling in adult physiology as well as in pathological conditions, including cancer development and metastasis. TSPs are active in bone remodeling, the process of bone resorption (osteolysis) and deposition (osteogenesis) that maintains bone homeostasis. TSPs are particularly involved in aberrant bone remodeling, including osteolytic and osteoblastic skeletal cancer metastasis, frequent in advanced cancers such as breast and prostate carcinoma...
September 16, 2020: American Journal of Physiology. Cell Physiology
Shiyuan Huang, Xiaona Wang, Jiale Yu, Yu Tian, Chenkai Yang, Yang Chen, Hua Chen, Hongshan Ge
Myoblast differentiation is a crucial process for myogenesis. Mitochondria function as an energy-providing machine that is critical to this process, and mitochondrial dysfunction can prevent myoblasts from fusing into myotubes. However, the molecular mechanisms underlying the dynamic regulation of mitochondrial networks remain poorly understood. In the present study, we found that the PTEN induced kinase 1(PINK1) /Parkin (an E3 ubiquitin-protein ligase) pathway is activated at the early stage of myoblast differentiation...
September 16, 2020: American Journal of Physiology. Cell Physiology
Alexandra M Kraft, Howard R Petty
Some patients treated for ductal carcinoma in situ (DCIS) of the breast will experience cancer recurrences, whereas other patients will not. Unfortunately, current techniques cannot identify which pre-invasive lesions will lead to recurrent cancer. Because the mechanism of cancer recurrence is unknown, it is difficult to design a test that detects its activity. We propose that certain pentose phosphate pathway enzymes, glutathione synthesis enzymes, and RhoA cluster at the epithelial cell periphery during cancer recurrences...
September 9, 2020: American Journal of Physiology. Cell Physiology
Qian Chen, Yuru Liu
Alveoli are the gas-exchanging units of the lung and alveolar barrier is often a key battleground that encounters pathogens, allergens, and other insults from the environment. This is seen in the current COVID-19 pandemic, as alveolar epithelium is one of the major targets of SARS-COV-2, the virus that causes COVID-19. Thus, it is essential to understand the mechanisms to maintain the integrity of alveoli epithelium. Alveolar type II (AT2) cells behave as tissue stem cells that repair alveoli epithelium in steady-state replacement and after injury...
September 9, 2020: American Journal of Physiology. Cell Physiology
Andrea J De Micheli, Jacob B Swanson, Nathaniel P Disser, Leandro M Martinez, Nicholas R Walker, David J Oliver, Benjamin D Cosgrove, Christopher L Mendias
Tendon is a dense connective tissue that stores and transmits forces between muscles and bones. Cellular heterogeneity is increasingly recognized as an important factor in the biological basis of tissue homeostasis and disease, yet little is known about the diversity of cell types that populate tendon. To address this, we determined the heterogeneity of cell populations within mouse Achilles tendons using single-cell RNA sequencing. In assembling a transcriptomic atlas of Achilles tendons, we identified 11 distinct types of cells, including 3 previously undescribed populations of tendon fibroblasts...
September 2, 2020: American Journal of Physiology. Cell Physiology
Florian A Britto, Karine Dumas, Sophie Giorgetti-Peraldi, Vincent Ollendorff, Francois B Favier
The Akt/mTOR signaling pathway governs macromolecules synthesis, cell growth and metabolism in response to nutrients and growth factors. REDD1 is a conserved and ubiquitous protein, which is transiently induced in response to multiple stimuli. Acting like an endogenous inhibitor of the Akt/mTOR signaling pathway, REDD1 protein has been shown to regulate cell growth, mitochondrial function, oxidative stress and apoptosis. Recent studies also indicate that timely REDD1 expression limits Akt/mTOR-dependent synthesis processes to spare energy during metabolic stresses, avoiding energy collapse and detrimental consequences...
September 2, 2020: American Journal of Physiology. Cell Physiology
Kyle I Mentkowski, Lindsey M Euscher, Akshar Patel, B Rita Alevriadou, Jennifer K Lang
Monocytes are critical mediators of the inflammatory response following myocardial infarction (MI) and ischemia-reperfusion injury. They are involved in both initiation and resolution of inflammation and play an integral role in cardiac repair. The antagonistic nature of their function is dependent on their subset heterogeneity and biphasic response following injury. New advancements in single-cell transcriptomics and mass cytometry have allowed us to identify smaller, transcriptionally distinct clusters which may have functional relevance in disease and homeostasis...
September 2, 2020: American Journal of Physiology. Cell Physiology
Heath G Gasier, Jacob Dohl, Hagir B Suliman, Claude A Piantadosi, Tianzheng Yu
Nutrient excess increases skeletal muscle oxidant production and mitochondrial fragmentation that may result in impaired mitochondrial function, a hallmark of skeletal muscle insulin resistance. This led us to explore whether an endogenous gas molecule, carbon monoxide (CO), which is thought to prevent weight gain and metabolic dysfunction in mice consuming high-fat diets, alters mitochondrial morphology and respiration in C2C12 myoblasts exposed to high-glucose (15.6 mM) and high-fat (250 µM BSA-palmitate) (HGHF)...
August 26, 2020: American Journal of Physiology. Cell Physiology
Suli Zhang, Marcelo G Kazanietz, Mariana Cooke
Tunneling nanotubes (TNTs) emerged as important specialized actin-rich membrane protrusions for cell-to-cell communication. These structures allow the intercellular exchange of material, such as ions, soluble proteins, receptors, vesicles and organelles, therefore exerting critical roles in normal cell function. Indeed, TNTs participate in a number of physiological processes, including embryogenesis, immune response and osteoclastogenesis. TNTs have been also shown to contribute to the transmission of retroviruses (e...
August 26, 2020: American Journal of Physiology. Cell Physiology
Kyoko Imanaka-Yoshida, Isao Tawara, Toshimichi Yoshida
Tenascin-C (TNC) is a large extracellular matrix glycoprotein classified as a matricellular protein that is generally up-regulated at high levels during physiological and pathological tissue remodelingand is involved in important biological signaling pathways.In the heart, TNC is transiently expressed at several important steps during embryonic development and is sparsely detected in normal adult heart, but is re-expressedin a spatiotemporally restricted manner under pathological conditions associated with inflammation, such as myocardial infarction, hypertensive cardiac fibrosis, myocarditis, dilated cardiomyopathy, and Kawasaki disease...
August 26, 2020: American Journal of Physiology. Cell Physiology
Brandon E McFarlin, Yuhan Chen, Taylor S Priver, Donna L Ralph, Adriana Mercado, Gerardo Gamba, Meena S Madhur, Alicia A McDonough
Extracellular fluid (ECF) [K+ ] is maintained by adaptations of kidney and skeletal muscle, responses heretofore studied separately. We aimed to determine how these organ systems work in concert to preserve ECF [K+ ] in male C57BL/6J mice fed a K+ deficient diet (0K) versus 1% K+ diet (1K) for 10 days (n=5-6/group). During 0K feeding, plasma [K+ ] fell from 4.5 to 2 mM; hindlimb muscle (gastrocnemius and soleus) lost 28 mM K+ (from 115 ± 2 to 87 ± 2 mM) and gained 27 mM Na+ (from 27 ± 0.4 to 54 ± 2 mM)...
August 26, 2020: American Journal of Physiology. Cell Physiology
Fang Zhang, Shuo Chen, Ji-Yue Wen, Zhi-Wu Chen
3-mercaptopyruvate sulfurtransferase (3-MST) is the major source of hydrogen sulfide (H2 S) production in the brain and participates in many physiological and pathological processes. The present study was designed to investigate the role of 3-MST-derived H2 S (3-MST/H2 S) on oxygen-glucose deprivation/reoxygenation (OGD/R) injury in cerebrovascular endothelial cells (ECs). Using cerebrovascular specimens from patients with acute massive cerebral infarction (MCI), we found abnormal morphology of the endothelium and mitochondria, as well as decreases in H2 S and 3-MST levels...
August 19, 2020: 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
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