Ethanol: Novel Actions on Nerve Cell Physiology Explain Impaired Functions

Physiology ◽  
1998 ◽  
Vol 13 (4) ◽  
pp. 164-170 ◽  
Author(s):  
Esa R. Korpi ◽  
Riikka Mäkelä ◽  
Mikko Uusi-Oukari
Keyword(s):  
Nerve Cell ◽  
Cell Membranes ◽  
Cell Physiology ◽  
Inhibitory Neurotransmitters ◽  
Receptor Proteins ◽  
Physiological Processes ◽  
Firm Basis

Molecular biological tools have revealed receptor proteins for excitatory and inhibitory neurotransmitters on cell membranes as targets of ethanol action. Behavioral and pharmacogenetic assays using rodent lines have supported this neurotransmitter theory of ethanol action and given a firm basis for future identification of the relevant genes and the central physiological processes vulnerable to ethanol.

Localization and quantification of endoplasmic reticulum Ca(2+)-ATPase isoform transcripts

1995 ◽  
Vol 269 (3) ◽  
pp. C775-C784 ◽  
Author(s):  
K. D. Wu ◽  
W. S. Lee ◽  
J. Wey ◽  
D. Bungard ◽  
J. Lytton
Keyword(s):  
Endoplasmic Reticulum ◽  
Critical Role ◽  
Qualitative Assessment ◽  
Cell Physiology ◽  
Striated Muscles ◽  
Physiological Processes ◽  
Alternatively Spliced ◽  
Spleen Lymphocytes ◽  
Fast Twitch ◽  
In Cells

The Ca(2+)-adenosinetriphosphatase pump of the sarcoplasmic or endoplasmic reticulum (SERCA) plays a critical role in Ca2+ signaling and homeostasis in all cells and is encoded by a family of homologous and alternatively spliced genes. To understand more clearly the role the different isoforms play in cell physiology, we have undertaken a quantitative and qualitative assessment of the tissue distribution of transcripts encoding each SERCA isoform. SERCA1 expression is restricted to fast-twitch striated muscles, SERCA2a to cardiac and slow-twitch striated muscles, whereas SERCA2b is ubiquitously expressed. SERCA3 is expressed most abundantly in large and small intestine, thymus, and cerebellum and at lower levels in spleen, lymph node, and lung. In situ hybridization analyses revealed SERCA3 transcripts in cells of the intestinal crypt, the thymic cortex, and Purkinje cells in cerebellum. In addition, SERCA3 was expressed abundantly in isolated rat spleen lymphocytes, in various murine lymphoid cell lines, and in primary cultured microvascular endothelial cells. This analysis demonstrates that SERCA3 is expressed selectively in cells in which Ca2+ signaling plays a critical and sensitive role in regulating physiological processes.

Disturbed Ion Gradients in Brain Anoxia

Physiology ◽  
1987 ◽  
Vol 2 (2) ◽  
pp. 54-57 ◽  
Author(s):  
AJ Hansen
Keyword(s):  
Blood Flow ◽  
Sodium Chloride ◽  
Synaptic Transmission ◽  
Nerve Cell ◽  
Nerve Conduction ◽  
Brain Function ◽  
Cell Membranes ◽  
Interstitial Fluid ◽  
Potassium Conductance ◽  
Ion Gradients

Anoxia profundly affects brain function. If the blood flow is interrupted for a few minutes, the interstitial fluid shows a dramatic increase of potassium and lowering of sodium, chloride, and calcium concentrations, which lead to arrest of nerve conduction and synaptic transmission. These changes, however, cannot explain that consciousness is lost within seconds. This may be caused by activation of potassium conductance in nerve cell membranes.

A proposed noise mechanism in nerve cell membranes

1974 ◽  
Vol 45 (2) ◽  
pp. 405-409 ◽  
Author(s):  
Ingemar Lundström ◽  
Douglas McQueen
Keyword(s):  
Nerve Cell ◽  
Cell Membranes

Bicarbonate transport in cell physiology and disease

2008 ◽  
Vol 417 (2) ◽  
pp. 423-439 ◽  
Author(s):  
Emmanuelle Cordat ◽  
Joseph R. Casey
Keyword(s):  
Waste Product ◽  
Transport Proteins ◽  
Whole Body ◽  
Bicarbonate Transport ◽  
Cell Physiology ◽  
Ph Buffering ◽  
Physiological Processes ◽  
Organ Systems ◽  
Wide Range ◽  
The Family

The family of mammalian bicarbonate transport proteins are involved in a wide-range of physiological processes. The importance of bicarbonate transport follows from the biochemistry of HCO3− itself. Bicarbonate is the waste product of mitochondrial respiration. HCO3− undergoes pH-dependent conversion into CO2 and in doing so converts from a membrane impermeant anion into a gas that can diffuse across membranes. The CO2–HCO3− equilibrium forms the most important pH buffering system of our bodies. Bicarbonate transport proteins facilitate the movement of membrane-impermeant HCO3− across membranes to accelerate disposal of waste CO2, control cellular and whole-body pH, and to regulate fluid movement and acid/base secretion. Defects of bicarbonate transport proteins manifest in diseases of most organ systems. Fourteen gene products facilitate mammalian bicarbonate transport, whose physiology and pathophysiology is discussed in the present review.

scholarly journals Evolved, Selective Erasers of Distinct Lysine Acylations

2019 ◽  
Author(s):  
Martin Spinck ◽  
Maria Ecke ◽  
Raphael Gasper ◽  
Heinz Neumann
Keyword(s):  
Conformational Changes ◽  
Metabolic Diseases ◽  
Great Part ◽  
Cellular Level ◽  
Cell Physiology ◽  
Post Translational Modification ◽  
Physiological Processes ◽  
Lysine Residues ◽  
Small Set ◽  
Lysine Deacetylases

AbstractLysine acetylation, including related lysine modifications such as butyrylation and crotonylation, is a widespread post-translational modification with important roles in many important physiological processes. However, uncovering the regulatory mechanisms that govern the reverse process, deacylation, has been challenging to address, in great part because the small set of lysine deacetylases (KDACs) that remove the modifications are promiscuous in their substrate and acylation-type preference. This lack of selectivity hinders a broader understanding of how deacylation is regulated at the cellular level and how it is correlated with lysine deacylation-related diseases. To facilitate the dissection of KDACs with respect to substrate specificity and modification type, it would be beneficial to re-engineer KDACs to be selective towards a given substrate and/or modification. To dissect the differential contributions of various acylations to cell physiology, we developed a novel directed evolution approach to create selective KDAC variants that are up to 400-fold selective towards butyryl- over crotonyl-lysine substrates. Structural analyses of this non-promiscuous KDAC revealed unprecedented insights regarding the conformational changes mediating the gain in specificity. As a second case study to illustrate the power of this approach, we re-engineer the human SirT1 to increase its selectivity towards acetylated versus crotonylated substrates. These new enzymes, as well as the generic approach that we report here, will greatly facilitate the dissection of the differential roles of lysine acylation in cell physiology.Significance StatementAcetylation of lysine residues features numerous roles in diverse physiological processes and correlates with the manifestation of metabolic diseases, cancer and ageing. The already huge diversity of the acetylome is multiplied by variations in the types of acylation. This complexity is in stark contrast to the small set of lysine deacetylases (KDACs) present in human cells, anticipating a pronounced substrate promiscuity.We device a strategy to tackle this disarray by creating KDAC variants with increased selectivity towards particular types of lysine acylations using a novel selection system. The variants facilitate the dissection of the differential contributions of particular acylations to gene expression, development and disease. Our structural analyses shed light on the mechanism of substrate discrimination by Sirtuin-type KDACs.

scholarly journals The Tumor Suppressor Roles of MYBBP1A, a Major Contributor to Metabolism Plasticity and Stemness

Cancers ◽  
2020 ◽  
Vol 12 (1) ◽  
pp. 254 ◽  
Author(s):  
Blanca Felipe-Abrio ◽  
Amancio Carnero
Keyword(s):  
Cell Cycle ◽  
Stem Cell ◽  
Tumor Suppressor ◽  
Selective Advantage ◽  
Renal Tumors ◽  
Stem Cell Population ◽  
Tumor Stem Cell ◽  
Cell Physiology ◽  
Major Contributor ◽  
Physiological Processes

The MYB binding protein 1A (MYBBP1A, also known as p160) acts as a co-repressor of multiple transcription factors involved in many physiological processes. Therefore, MYBBP1A acts as a tumor suppressor in multiple aspects related to cell physiology, most of them very relevant for tumorigenesis. We explored the different roles of MYBBP1A in different aspects of cancer, such as mitosis, cellular senescence, epigenetic regulation, cell cycle, metabolism plasticity and stemness. We especially reviewed the relationships between MYBBP1A, the inhibitory role it plays by binding and inactivating c-MYB and its regulation of PGC-1α, leading to an increase in the stemness and the tumor stem cell population. In addition, MYBBP1A causes the activation of PGC-1α directly and indirectly through c-MYB, inducing the metabolic change from glycolysis to oxidative phosphorylation (OXPHOS). Therefore, the combination of these two effects caused by the decreased expression of MYBBP1A provides a selective advantage to tumor cells. Interestingly, this only occurs in cells lacking pVHL. Finally, the loss of MYBBP1A occurs in 8%–9% of renal tumors. tumors, and this subpopulation could be studied as a possible target of therapies using inhibitors of mitochondrial respiration.

scholarly journals Alternative Splicing by NOVA Factors: From Gene Expression to Cell Physiology and Pathology

2020 ◽  
Vol 21 (11) ◽  
pp. 3941 ◽  
Author(s):  
Jacopo Meldolesi
Keyword(s):  
Alternative Splicing ◽  
Migration And Invasion ◽  
Cell Physiology ◽  
Axon Pathfinding ◽  
Surface Receptors ◽  
Cell Functions ◽  
Physiological Processes ◽  
Voltage Gated Channels ◽  
And Function ◽  
Near Future

NOVA1 and NOVA2, the two members of the NOVA family of alternative splicing factors, bind YCAY clusters of pre-mRNAs and assemble spliceosomes to induce the maintenance/removal of introns and exons, thus governing the development of mRNAs. Members of other splicing families operate analogously. Activity of NOVAs accounts for up to 700 alternative splicing events per cell, taking place both in the nucleus (co-transcription of mRNAs) and in the cytoplasm. Brain neurons express high levels of NOVAs, with NOVA1 predominant in cerebellum and spinal cord, NOVA2 in the cortex. Among brain physiological processes NOVAs play critical roles in axon pathfinding and spreading, structure and function of synapses, as well as the regulation of surface receptors and voltage-gated channels. In pathology, NOVAs contribute to neurodegenerative diseases and epilepsy. In vessel endothelial cells, NOVA2 is essential for angiogenesis, while in adipocytes, NOVA1 contributes to regulation of thermogenesis and obesity. In many cancers NOVA1 and also NOVA2, by interacting with specific miRNAs and by additional mechanisms, activate oncogenic roles promoting cell proliferation, colony formation, migration, and invasion. In conclusion, NOVAs regulate cell functions of physiological and pathological nature. Single cell identification and distinction, and new therapies addressed to NOVA targets might be developed in the near future.

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