scholarly journals CaMKII oxidation is a performance/disease trade-off in vertebrate evolution

2019 ◽  
Author(s):  
Qinchuan Wang ◽  
Erick O. Hernández-Ochoa ◽  
Meera C. Viswanathan ◽  
Ian D. Blum ◽  
Jonathan M. Granger ◽  
...  
Keyword(s):  
Comparative Genomic ◽  
Behavioural Ecology ◽  
Oxygen Species ◽  
Trade Off ◽  
Stem Lineage ◽  
Intracellular Ca ◽  
Health And Disease ◽  
Evolutionary Success ◽  
Improved Performance ◽  
Camkii Activation

Reactive oxygen species (ROS) contribute to health and disease. CaMKII is a widely expressed enzyme whose activation by oxidation of regulatory domain methionines (ox-CaMKII) contributes to cardiovascular disease, asthma, and cancer. Here we integrate comparative genomic and experimental data to show that CaMKII activation by ROS arose more than half-a-billion years ago on the vertebrate stem lineage where it constituted a bridge between ROS and increased intracellular Ca2+ release, exercise responsive gene transcription, and improved performance in skeletal muscle. These enhancements to fight-or-flight physiology were likely key in facilitating a well-evidenced shift in the behavioural ecology of our immediate chordate ancestors, and, in turn, the evolutionary success of vertebrates. Still, the ox-CaMKII innovation for augmenting performance must be considered a critical evolutionary trade-off, as it rendered us more susceptible to common and often fatal diseases linked to excessive ROS.

scholarly journals CaMKII oxidation is a critical performance/disease trade-off acquired at the dawn of vertebrate evolution

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Qinchuan Wang ◽  
Erick O. Hernández-Ochoa ◽  
Meera C. Viswanathan ◽  
Ian D. Blum ◽  
Danh C. Do ◽  
...  
Keyword(s):  
Genetically Engineered ◽  
Antagonistic Pleiotropy ◽  
Genetic Traits ◽  
Trade Off ◽  
Enhanced Sensitivity ◽  
Genetically Engineered Mice ◽  
Stem Lineage ◽  
Intracellular Ca ◽  
Evolutionary Success ◽  
Positive Traits

AbstractAntagonistic pleiotropy is a foundational theory that predicts aging-related diseases are the result of evolved genetic traits conferring advantages early in life. Here we examine CaMKII, a pluripotent signaling molecule that contributes to common aging-related diseases, and find that its activation by reactive oxygen species (ROS) was acquired more than half-a-billion years ago along the vertebrate stem lineage. Functional experiments using genetically engineered mice and flies reveal ancestral vertebrates were poised to benefit from the union of ROS and CaMKII, which conferred physiological advantage by allowing ROS to increase intracellular Ca2+ and activate transcriptional programs important for exercise and immunity. Enhanced sensitivity to the adverse effects of ROS in diseases and aging is thus a trade-off for positive traits that facilitated the early and continued evolutionary success of vertebrates.

scholarly journals Reactive Oxygen Species: Beyond Their Reactive Behavior

2021 ◽  
Vol 46 (1) ◽  
pp. 77-87
Author(s):  
Arnaud Tauffenberger ◽  
Pierre J. Magistretti
Keyword(s):  
Reactive Oxygen Species ◽  
Second Messengers ◽  
Critical Role ◽  
Complex Function ◽  
Reactive Oxygen ◽  
High Reactivity ◽  
Oxygen Species ◽  
Health And Disease ◽  
Cellular Dysfunction ◽  
The Brain

AbstractCellular homeostasis plays a critical role in how an organism will develop and age. Disruption of this fragile equilibrium is often associated with health degradation and ultimately, death. Reactive oxygen species (ROS) have been closely associated with health decline and neurological disorders, such as Alzheimer’s disease or Parkinson’s disease. ROS were first identified as by-products of the cellular activity, mainly mitochondrial respiration, and their high reactivity is linked to a disruption of macromolecules such as proteins, lipids and DNA. More recent research suggests more complex function of ROS, reaching far beyond the cellular dysfunction. ROS are active actors in most of the signaling cascades involved in cell development, proliferation and survival, constituting important second messengers. In the brain, their impact on neurons and astrocytes has been associated with synaptic plasticity and neuron survival. This review provides an overview of ROS function in cell signaling in the context of aging and degeneration in the brain and guarding the fragile balance between health and disease.

scholarly journals Cardiac small-conductance calcium-activated potassium channels in health and disease

2021 ◽  
Vol 473 (3) ◽  
pp. 477-489 ◽  
Author(s):  
Xiao-Dong Zhang ◽  
Phung N. Thai ◽  
Deborah K. Lieu ◽  
Nipavan Chiamvimonvat
Keyword(s):  
Ventricular Myocytes ◽  
Pulmonary Veins ◽  
Differential Sensitivity ◽  
Sk Channels ◽  
Sk Channel ◽  
Ventricular Cells ◽  
Intracellular Ca ◽  
Life Threatening ◽  
Health And Disease ◽  
Small Conductance

AbstractSmall-conductance Ca2+-activated K+ (SK, KCa2) channels are encoded by KCNN genes, including KCNN1, 2, and 3. The channels play critical roles in the regulation of cardiac excitability and are gated solely by beat-to-beat changes in intracellular Ca2+. The family of SK channels consists of three members with differential sensitivity to apamin. All three isoforms are expressed in human hearts. Studies over the past two decades have provided evidence to substantiate the pivotal roles of SK channels, not only in healthy heart but also with diseases including atrial fibrillation (AF), ventricular arrhythmia, and heart failure (HF). SK channels are prominently expressed in atrial myocytes and pacemaking cells, compared to ventricular cells. However, the channels are significantly upregulated in ventricular myocytes in HF and pulmonary veins in AF models. Interests in cardiac SK channels are further fueled by recent studies suggesting the possible roles of SK channels in human AF. Therefore, SK channel may represent a novel therapeutic target for atrial arrhythmias. Furthermore, SK channel function is significantly altered by human calmodulin (CaM) mutations, linked to life-threatening arrhythmia syndromes. The current review will summarize recent progress in our understanding of cardiac SK channels and the roles of SK channels in the heart in health and disease.

scholarly journals Comparative genomic and transcriptomic analyses of transposable elements in polychaetous annelids highlight LTR retrotransposon diversity and evolution

Mobile DNA ◽  
2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Jonathan Filée ◽  
Sarah Farhat ◽  
Dominique Higuet ◽  
Laure Teysset ◽  
Dominique Marie ◽  
...  
Keyword(s):  
Transposable Elements ◽  
High Throughput Sequencing ◽  
Comparative Genomic ◽  
Ltr Retrotransposon ◽  
Genomic Evolution ◽  
Genome Wide ◽  
Genomic Analyses ◽  
Different Types ◽  
Evolutionary Success ◽  
Low Coverage

Abstract Background With the expansion of high throughput sequencing, we now have access to a larger number of genome-wide studies analyzing the Transposable elements (TEs) composition in a wide variety of organisms. However, genomic analyses often remain too limited in number and diversity of species investigated to study in depth the dynamics and evolutionary success of the different types of TEs among metazoans. Therefore, we chose to investigate the use of transcriptomes to describe the diversity of TEs in phylogenetically related species by conducting the first comparative analysis of TEs in two groups of polychaetes and evaluate the diversity of TEs that might impact genomic evolution as a result of their mobility. Results We present a detailed analysis of TEs distribution in transcriptomes extracted from 15 polychaetes depending on the number of reads used during assembly, and also compare these results with additional TE scans on associated low-coverage genomes. We then characterized the clades defined by 1021 LTR-retrotransposon families identified in 26 species. Clade richness was highly dependent on the considered superfamily. Copia elements appear rare and are equally distributed in only three clades, GalEa, Hydra and CoMol. Among the eight BEL/Pao clades identified in annelids, two small clades within the Sailor lineage are new for science. We characterized 17 Gypsy clades of which only 4 are new; the C-clade largely dominates with a quarter of the families. Finally, all species also expressed for the majority two distinct transcripts encoding PIWI proteins, known to be involved in control of TEs mobilities. Conclusions This study shows that the use of transcriptomes assembled from 40 million reads was sufficient to access to the diversity and proportion of the transposable elements compared to those obtained by low coverage sequencing. Among LTR-retrotransposons Gypsy elements were unequivocally dominant but results suggest that the number of Gypsy clades, although high, may be more limited than previously thought in metazoans. For BEL/Pao elements, the organization of clades within the Sailor lineage appears more difficult to establish clearly. The Copia elements remain rare and result from the evolutionary consistent success of the same three clades.

Subversion of host cell signalling by the protozoan parasiteLeishmania

Parasitology ◽  
2005 ◽  
Vol 130 (S1) ◽  
pp. S27-S35 ◽  
Author(s):  
D. J. GREGORY ◽  
M. OLIVIER
Keyword(s):  
Nitric Oxide ◽  
Reactive Oxygen Species ◽  
Cell Signalling ◽  
Protein Tyrosine Phosphatases ◽  
Innate Immune ◽  
Signalling Pathways ◽  
Oxygen Species ◽  
Obligate Intracellular ◽  
Intracellular Parasites ◽  
Intracellular Ca

The protozoaLeishmaniaspp. are obligate intracellular parasites that inhabit the macrophages of their host. Since macrophages are specialized for the identification and destruction of invading pathogens, both directly and by triggering an innate immune response,Leishmaniahave evolved a number of mechanisms for suppressing some critical macrophage activities. In this review, we discuss how various species ofLeishmaniadistort the host macrophage's own signalling pathways to repress the expression of various cytokines and microbicidal molecules (nitric oxide and reactive oxygen species), and antigen presentation. In particular, we describe how MAP Kinase and JAK/STAT cascades are repressed, and intracellular Ca2+and the activities of protein tyrosine phosphatases, in particular SHP-1, are elevated.

scholarly journals Developmental plasticity of cardiac anoxia-tolerance in juvenile common snapping turtles ( Chelydra serpentina )

2019 ◽  
Vol 286 (1905) ◽  
pp. 20191072 ◽  
Author(s):  
Ilan M. Ruhr ◽  
Heather McCourty ◽  
Afaf Bajjig ◽  
Dane A. Crossley ◽  
Holly A. Shiels ◽  
...  
Keyword(s):  
Developmental Plasticity ◽  
Hypoxia Tolerance ◽  
Anoxia Tolerance ◽  
Ros Production ◽  
Oxygen Species ◽  
Early Exposure ◽  
Cellular Mechanisms ◽  
Isolated Cardiomyocytes ◽  
Intracellular Ca ◽  
The Common

For some species of ectothermic vertebrates, early exposure to hypoxia during embryonic development improves hypoxia-tolerance later in life. However, the cellular mechanisms underlying this phenomenon are largely unknown. Given that hypoxic survival is critically dependent on the maintenance of cardiac function, we tested the hypothesis that developmental hypoxia alters cardiomyocyte physiology in a manner that protects the heart from hypoxic stress. To test this hypothesis, we studied the common snapping turtle, which routinely experiences chronic developmental hypoxia and exploits hypoxic environments in adulthood. We isolated cardiomyocytes from juvenile turtles that embryonically developed in either normoxia (21% O 2 ) or hypoxia (10% O 2 ), and subjected them to simulated anoxia and reoxygenation, while simultaneously measuring intracellular Ca 2+ , pH and reactive oxygen species (ROS) production. Our results suggest developmental hypoxia improves cardiomyocyte anoxia-tolerance of juvenile turtles, which is supported by enhanced myofilament Ca 2+ -sensitivity and a superior ability to suppress ROS production. Maintenance of low ROS levels during anoxia might limit oxidative damage and a greater sensitivity to Ca 2+ could provide a mechanism to maintain contractile force. Our study suggests developmental hypoxia has long-lasting effects on turtle cardiomyocyte function, which might prime their physiology for exploiting hypoxic environments.

scholarly journals The inhibition of chloride intracellular channel 1 enhances Ca2+ and reactive oxygen species signaling in A549 human lung cancer cells

2019 ◽  
Vol 51 (7) ◽  
Author(s):  
Jae-Rin Lee ◽  
Jong-Yoon Lee ◽  
Hyun-Ji Kim ◽  
Myong-Joon Hahn ◽  
Jong-Sun Kang ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Reactive Oxygen Species ◽  
Cancer Cells ◽  
Human Lung ◽  
A549 Cells ◽  
Human Lung Cancer ◽  
Oxygen Species ◽  
Human Lung Cancer Cells ◽  
Intracellular Ca ◽  
Intracellular Channel

AbstractChloride intracellular channel 1 (CLIC1) is a promising therapeutic target in cancer due to its intrinsic characteristics; it is overexpressed in specific tumor types and its localization changes from cytosolic to surface membrane depending on activities and cell cycle progression. Ca2+ and reactive oxygen species (ROS) are critical signaling molecules that modulate diverse cellular functions, including cell death. In this study, we investigated the function of CLIC1 in Ca2+ and ROS signaling in A549 human lung cancer cells. Depletion of CLIC1 via shRNAs in A549 cells increased DNA double-strand breaks both under control conditions and under treatment with the putative anticancer agent chelerythrine, accompanied by a concomitant increase in the p-JNK level. CLIC1 knockdown greatly increased basal ROS levels, an effect prevented by BAPTA-AM, an intracellular calcium chelator. Intracellular Ca2+ measurements clearly showed that CLIC1 knockdown significantly increased chelerythrine-induced Ca2+ signaling as well as the basal Ca2+ level in A549 cells compared to these levels in control cells. Suppression of extracellular Ca2+ restored the basal Ca2+ level in CLIC1-knockdown A549 cells relative to that in control cells, implying that CLIC1 regulates [Ca2+]i through Ca2+ entry across the plasma membrane. Consistent with this finding, the L-type Ca2+ channel (LTCC) blocker nifedipine reduced the basal Ca2+ level in CLIC1 knockdown cells to that in control cells. Taken together, our results demonstrate that CLIC1 knockdown induces an increase in the intracellular Ca2+ level via LTCC, which then triggers excessive ROS production and consequent JNK activation. Thus, CLIC1 is a key regulator of Ca2+ signaling in the control of cancer cell survival.

Effects of Perceptual and Conceptual Processing on Memory for Words and Voice: Different Patterns for Young and Old

1996 ◽  
Vol 49 (3) ◽  
pp. 780-796 ◽  
Author(s):  
Moshe Naveh-Benjamin ◽  
Fergus I. M. Craik
Keyword(s):  
Age Groups ◽  
Memory Task ◽  
Recognition Task ◽  
Perceptual Processing ◽  
Trade Off ◽  
Conceptual Processing ◽  
Older Subjects ◽  
Improved Performance ◽  
The Voice ◽  
Two Age Groups

In two experiments younger and older adults listened to a list of words presented auditorily by two speakers. The subjects processed each word either perceptually (voice judgements) or conceptually (pleasantness judgements), and were then given memory tasks for the words and the presenting voice. In the word-recognition task the two age groups benefited equally from conceptual as opposed to perceptual processing. In the voice memory task, however, conceptual processing improved performance relative to perceptual processing in the younger subjects (significantly so in Experiment 1), but conceptual processing was associated with decreased performance in the older group (significantly so in Experiment 2). These results suggest that whereas older subjects exhibit a trade-off in memory for item and attribute information, younger subjects exhibit a pattern of support, in which conceptual processing benefits memory for both items and their attributes.

scholarly journals The Subcellular Localization of the Receptor for Platelet-Activating Factor in Neutrophils Affects Signaling and Activation Characteristics

2013 ◽  
Vol 2013 ◽  
pp. 1-11 ◽  
Author(s):  
Emil Andréasson ◽  
Karin Önnheim ◽  
Huamei Forsman
Keyword(s):  
Reactive Oxygen Species ◽  
Plasma Membrane ◽  
Subcellular Localization ◽  
Platelet Activating Factor ◽  
Subcellular Fractionation ◽  
Oxygen Species ◽  
High Affinity ◽  
Formyl Peptide ◽  
Intracellular Ca ◽  
Vesicle Secretion

The localization in neutrophils, of the receptor for platelet-activating factor (PAFR), has been determined using subcellular fractionation and a receptor mobilization protocol. We show that the PAFR is expressed primarily in the plasma membrane. Although activation of neutrophils by PAF induces responses typical also of agonists that bind the formyl peptide receptors (FPR), known to be stored in mobilizable organelles, some quantitative as well as qualitative differences were observed when neutrophils were activated through these receptors. PAF is equipotent to fMLF (high affinity agonist for FPR1) to cleave off L-selectin and to induce granule/vesicle secretion but is more potent than fMLF to induce a rise in intracellular Ca2+. Similar to fMLF, PAF induced also a robust release of reactive oxygen species, but with higher EC50value and was less sensitive to a PI3K inhibitor compared to the fMLF response. Despite the lack of a granule localized storage pool of receptors, the PAF-induced superoxide production could be primed; receptor mobilization was, thus, not required for priming of the PAF response. The desensitized PAFR could not be reactivated, suggesting that distinct signaling pathways are utilized for termination of the responses triggered through FPR1 and PAFR.

Sign in / Sign up

Export Citation Format

Share Document