Blockade of epithelial Na+ channels by triamterenes — Underlying mechanisms and molecular basis

1996 ◽  
Vol 432 (5) ◽  
pp. 760-766 ◽  
Author(s):  
A. E. Busch ◽  
H. Suessbrich ◽  
K. Kunzelmann ◽  
A. Hipper ◽  
R. Greger ◽  
...  
Keyword(s):  
Molecular Basis ◽  
Na Channels ◽  
Epithelial Na Channels ◽  
Underlying Mechanisms

scholarly journals Structural and Functional Remodeling of Mitochondria in Cardiac Diseases

2021 ◽  
Vol 22 (8) ◽  
pp. 4167
Author(s):  
Xiaonan Sun ◽  
Jalen Alford ◽  
Hongyu Qiu
Keyword(s):  
Regulatory Network ◽  
Molecular Basis ◽  
Therapeutic Potential ◽  
Research Direction ◽  
Future Research ◽  
Cardiac Diseases ◽  
Functional Remodeling ◽  
Underlying Mechanisms ◽  
Mitochondrial Remodeling ◽  
Normal Cellular Function

Mitochondria undergo structural and functional remodeling to meet the cell demand in response to the intracellular and extracellular stimulations, playing an essential role in maintaining normal cellular function. Merging evidence demonstrated that dysregulation of mitochondrial remodeling is a fundamental driving force of complex human diseases, highlighting its crucial pathophysiological roles and therapeutic potential. In this review, we outlined the progress of the molecular basis of mitochondrial structural and functional remodeling and their regulatory network. In particular, we summarized the latest evidence of the fundamental association of impaired mitochondrial remodeling in developing diverse cardiac diseases and the underlying mechanisms. We also explored the therapeutic potential related to mitochondrial remodeling and future research direction. This updated information would improve our knowledge of mitochondrial biology and cardiac diseases’ pathogenesis, which would inspire new potential strategies for treating these diseases by targeting mitochondria remodeling.

scholarly journals From Capsids to Complexes: Expanding the Role of TRIM5α in the Restriction of Divergent RNA Viruses and Elements

Viruses ◽  
2021 ◽  
Vol 13 (3) ◽  
pp. 446
Author(s):  
Kevin M. Rose ◽  
Stephanie J. Spada ◽  
Rebecca Broeckel ◽  
Kristin L. McNally ◽  
Vanessa M. Hirsch ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Molecular Basis ◽  
Human Population ◽  
Rna Viruses ◽  
Arms Race ◽  
Innate Immune ◽  
Immunodeficiency Virus ◽  
Underlying Mechanisms ◽  
Hiv 1

An evolutionary arms race has been ongoing between retroviruses and their primate hosts for millions of years. Within the last century, a zoonotic transmission introduced the Human Immunodeficiency Virus (HIV-1), a retrovirus, to the human population that has claimed the lives of millions of individuals and is still infecting over a million people every year. To counteract retroviruses such as this, primates including humans have evolved an innate immune sensor for the retroviral capsid lattice known as TRIM5α. Although the molecular basis for its ability to restrict retroviruses is debated, it is currently accepted that TRIM5α forms higher-order assemblies around the incoming retroviral capsid that are not only disruptive for the virus lifecycle, but also trigger the activation of an antiviral state. More recently, it was discovered that TRIM5α restriction is broader than previously thought because it restricts not only the human retroelement LINE-1, but also the tick-borne flaviviruses, an emergent group of RNA viruses that have vastly different strategies for replication compared to retroviruses. This review focuses on the underlying mechanisms of TRIM5α-mediated restriction of retroelements and flaviviruses and how they differ from the more widely known ability of TRIM5α to restrict retroviruses.

Mechanisms and sequelae of increased alveolar fluid clearance in hyperoxic rats

1997 ◽  
Vol 272 (3) ◽  
pp. L407-L412 ◽  
Author(s):  
G. Yue ◽  
S. Matalon
Keyword(s):  
Alveolar Epithelial Cells ◽  
Na Channels ◽  
Alveolar Fluid Clearance ◽  
Na Transport ◽  
Alveolar Epithelial ◽  
Lung Fluid ◽  
Isotonic Fluid ◽  
Epithelial Na Channels ◽  
Alveolar Edema

We instilled 4 ml isotonic fluid containing trace amounts of fluorescently labeled dextran (molecular mass 150 kDa) in the lungs of rats exposed to either 85% O(2) for 7 days or to 85% O(2) for 7 days and 100% O(2) for 3 days. We withdrew the fluid every hour for a 3-h period and calculated alveolar fluid clearance (AFC) from changes in dextran concentration. Postinstillation (3 h), AFC values in the control and the two hyperoxic groups were 51 +/- 1, 63 +/- 2, and 62 +/- 3 (SE), respectively (%instilled volume; n > or = 5; P < 0.05). Addition of either 1 mM amiloride or N-ethyl-N-isopropyl amiloride (EIPA) in the instillate decreased the AFC values in all groups 3 h later to approximately 30% of instilled volume. Instillation of phenamil, an irreversible blocker of epithelial Na+ channels into the lungs of rats exposed to 85% O(2) for 7 days and 100% O(2) for 2 days, resulted in a significant increase of their extravascular lung fluid volumes 24 h later. These results demonstrate the existence of EIPA-inhibitable Na+ channels in alveolar epithelial cells in vivo and indicate that an increase in Na+ transport plays an important role in limiting the amount of alveolar edema in O(2)-damaged lungs.

scholarly journals The Molecular Basis and Therapeutic Potential of Let-7 MicroRNAs against Colorectal Cancer

2018 ◽  
Vol 2018 ◽  
pp. 1-7 ◽  
Author(s):  
Rei Mizuno ◽  
Kenji Kawada ◽  
Yoshiharu Sakai
Keyword(s):  
Colorectal Cancer ◽  
Molecular Basis ◽  
Posttranscriptional Regulation ◽  
Therapeutic Agent ◽  
Therapeutic Potential ◽  
Noncoding Rnas ◽  
Intestinal Tumorigenesis ◽  
C Elegans ◽  
Microrna Family ◽  
Underlying Mechanisms

Although a number of studies have revealed the underlying mechanisms which regulate the development of colorectal cancer (CRC), we have not completely overcome this disease yet. Accumulating evidence has shown that the posttranscriptional regulation by the noncoding RNAs such as microRNAs plays an important role in the development or progression of CRC. Among a number of microRNAs, the let-7 microRNA family that was first discovered in C. elegans and conserved from worms to humans has been linked with the development of many types of cancers including CRC. The expression level of let-7 microRNAs is temporally low during the normal developmental processes, while elevated in the differentiated tissues. The let-7 microRNAs regulate the cell proliferation, cell cycle, apoptosis, metabolism, and stemness. In CRC, expressions of let-7 microRNAs have been reported to be reduced, and so let-7 microRNAs are considered to be a tumor suppressor. In this review, we discuss the mechanisms regulating the let-7 microRNA expression and the downstream targets of let-7 in the context of intestinal tumorigenesis. The application of let-7 mimics is also highlighted as a novel therapeutic agent.

scholarly journals Side Chain Orientation of Residues Lining the Selectivity Filter of Epithelial Na+Channels

2004 ◽  
Vol 280 (9) ◽  
pp. 8513-8522 ◽  
Author(s):  
Shaohu Sheng ◽  
Clint J. Perry ◽  
Ossama B. Kashlan ◽  
Thomas R. Kleyman
Keyword(s):  
Selectivity Filter ◽  
Side Chain ◽  
Na Channels ◽  
Chain Orientation ◽  
Epithelial Na Channels ◽  
Side Chain Orientation

scholarly journals Roles of the C Termini of α-, β-, and γ-Subunits of Epithelial Na+Channels (ENaC) in Regulating ENaC and Mediating Its Inhibition by Cytosolic Na+

2001 ◽  
Vol 276 (17) ◽  
pp. 13744-13749 ◽  
Author(s):  
Anuwat Dinudom ◽  
Kieran F. Harvey ◽  
Permsak Komwatana ◽  
Corina N. Jolliffe ◽  
John A. Young ◽  
...  
Keyword(s):  
Na Channels ◽  
Epithelial Na Channels

scholarly journals Na restriction activates epithelial Na channels in rat kidney through two mechanisms and decreases distal Na+ delivery

2018 ◽  
Vol 596 (16) ◽  
pp. 3585-3602 ◽  
Author(s):  
Gustavo Frindt ◽  
Lei Yang ◽  
Krister Bamberg ◽  
Lawrence G. Palmer
Keyword(s):  
Rat Kidney ◽  
Na Channels ◽  
Epithelial Na Channels

scholarly journals Molecular mechanisms of telomere biology disorders

2020 ◽  
pp. jbc.REV120.014017
Author(s):  
Sherilyn Grill ◽  
Jayakrishnan Nandakumar
Keyword(s):  
Molecular Basis ◽  
Molecular Mechanisms ◽  
Wide Spectrum ◽  
Significant Proportion ◽  
Dyskeratosis Congenita ◽  
Telomere Maintenance ◽  
Genetic Mutations ◽  
Hematopoietic Stem ◽  
Telomere Biology ◽  
Underlying Mechanisms

Genetic mutations that affect telomerase function or telomere maintenance result in a variety of diseases collectively called telomeropathies. This wide spectrum of disorders, which include dyskeratosis congenita (DC), pulmonary fibrosis (PF) and aplastic anemia (AA), is characterized by severely short telomeres, often resulting in hematopoietic stem cell failure in the most severe cases. Recent work has focused on understanding the molecular basis of these diseases. Mutations in the catalytic TERT and TR subunits of telomerase compromise activity, while others, such as those found in the telomeric protein TPP1, reduce the recruitment of telomerase to the telomere. Mutant telomerase-associated proteins TCAB1 and dyskerin, and the telomerase RNA maturation component PARN, affect the maturation and stability of telomerase. In contrast, disease-associated mutations in either CTC1 or RTEL1 are more broadly associated with telomere replication defects. Yet even with the recent surge in studies decoding the mechanisms underlying these diseases, a significant proportion of DC mutations remain uncharacterized or poorly understood. Here we review the current understanding of the molecular basis of telomeropathies and highlight experimental data that illustrate how genetic mutations drive telomere shortening and dysfunction in these patients. This review connects insights from both clinical and molecular studies to create a comprehensive view of the underlying mechanisms that drive these diseases. Through this, we emphasize recent advances in therapeutics and pin-point disease-associated variants that remain poorly defined in their mechanism of action. Finally, we suggest future avenues of research that will deepen our understanding of telomere biology and telomere-related disease.

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