scholarly journals Understanding Key Mechanisms of Exercise-Induced Cardiac Protection to Mitigate Disease: Current Knowledge and Emerging Concepts

2018 ◽  
Vol 98 (1) ◽  
pp. 419-475 ◽  
Author(s):  
Bianca C. Bernardo ◽  
Jenny Y. Y. Ooi ◽  
Kate L. Weeks ◽  
Natalie L. Patterson ◽  
Julie R. McMullen
Keyword(s):  
Stress Responses ◽  
Molecular Mechanisms ◽  
Cardiac Myocyte ◽  
Current Knowledge ◽  
Depth Profiling ◽  
Ubiquitin Proteasome System ◽  
Cardiac Cells ◽  
Cell Organelle ◽  
Cardiac Protection ◽  
Exercise Induced

The benefits of exercise on the heart are well recognized, and clinical studies have demonstrated that exercise is an intervention that can improve cardiac function in heart failure patients. This has led to significant research into understanding the key mechanisms responsible for exercise-induced cardiac protection. Here, we summarize molecular mechanisms that regulate exercise-induced cardiac myocyte growth and proliferation. We discuss in detail the effects of exercise on other cardiac cells, organelles, and systems that have received less or little attention and require further investigation. This includes cardiac excitation and contraction, mitochondrial adaptations, cellular stress responses to promote survival (heat shock response, ubiquitin-proteasome system, autophagy-lysosomal system, endoplasmic reticulum unfolded protein response, DNA damage response), extracellular matrix, inflammatory response, and organ-to-organ crosstalk. We summarize therapeutic strategies targeting known regulators of exercise-induced protection and the challenges translating findings from bench to bedside. We conclude that technological advancements that allow for in-depth profiling of the genome, transcriptome, proteome and metabolome, combined with animal and human studies, provide new opportunities for comprehensively defining the signaling and regulatory aspects of cell/organelle functions that underpin the protective properties of exercise. This is likely to lead to the identification of novel biomarkers and therapeutic targets for heart disease.

scholarly journals Endoplasmic reticulum and the microRNA environment in the cardiovascular system

2019 ◽  
Vol 97 (6) ◽  
pp. 515-527 ◽  
Author(s):  
Jody Groenendyk ◽  
Xiao Fan ◽  
Zhenling Peng ◽  
Lukasz Kurgan ◽  
Marek Michalak
Keyword(s):  
Endoplasmic Reticulum ◽  
Cardiovascular System ◽  
Stress Responses ◽  
Cardiac Myocyte ◽  
Cellular Stress ◽  
Cardiac Cells ◽  
Stress Coping ◽  
Coping Responses ◽  
The Unfolded Protein Response ◽  
The Impact

Stress responses are important to human physiology and pathology, and the inability to adapt to cellular stress leads to cell death. To mitigate cellular stress and re-establish homeostasis, cells, including those in the cardiovascular system, activate stress coping response mechanisms. The endoplasmic reticulum, a component of the cellular reticular network in cardiac cells, mobilizes so-called endoplasmic reticulum stress coping responses, such as the unfolded protein response. MicroRNAs play an important part in the maintenance of cellular and tissue homeostasis, perform a central role in the biology of the cardiac myocyte, and are involved in pathological cardiac function and remodeling. In this paper, we review a link between endoplasmic reticulum homeostasis and microRNA with an emphasis on the impact on stress responses in the cardiovascular system.

scholarly journals Roles and Mechanisms of Deubiquitinases (DUBs) in Breast Cancer Progression and Targeted Drug Discovery

Life ◽  
2021 ◽  
Vol 11 (9) ◽  
pp. 965
Author(s):  
Sixuan Li ◽  
Hongquan Zhang ◽  
Xiaofan Wei
Keyword(s):  
Breast Cancer ◽  
Cancer Progression ◽  
Drug Targets ◽  
Molecular Mechanisms ◽  
Current Knowledge ◽  
Tumor Development ◽  
Ubiquitin Proteasome System ◽  
Prognostic Indicators ◽  
Breast Cancer Patients ◽  
Oncogenic Signaling

Deubiquitinase (DUB) is an essential component in the ubiquitin—proteasome system (UPS) by removing ubiquitin chains from substrates, thus modulating the expression, activity, and localization of many proteins that contribute to tumor development and progression. DUBs have emerged as promising prognostic indicators and drug targets. DUBs have shown significant roles in regulating breast cancer growth, metastasis, resistance to current therapies, and several canonical oncogenic signaling pathways. In addition, specific DUB inhibitors have been identified and are expected to benefit breast cancer patients in the future. Here, we review current knowledge about the effects and molecular mechanisms of DUBs in breast cancer, providing novel insight into treatments of breast cancer-targeting DUBs.

Significance of silicon uptake, transport, and deposition in plants

2020 ◽  
Vol 71 (21) ◽  
pp. 6703-6718 ◽  
Author(s):  
Rushil Mandlik ◽  
Vandana Thakral ◽  
Gaurav Raturi ◽  
Suhas Shinde ◽  
Miroslav Nikolić ◽  
...  
Keyword(s):  
Stress Responses ◽  
Molecular Mechanisms ◽  
Developmental Stages ◽  
Current Knowledge ◽  
Cell Types ◽  
Detailed Knowledge ◽  
Beneficial Effects ◽  
Physiological Processes ◽  
Silicon Uptake ◽  
Different Tissues

Abstract Numerous studies have shown the beneficial effects of silicon (Si) for plant growth, particularly under stress conditions, and hence a detailed understanding of the mechanisms of its uptake, subsequent transport, and accumulation in different tissues is important. Here, we provide a thorough review of our current knowledge of how plants benefit from Si supplementation. The molecular mechanisms involved in Si transport are discussed and we highlight gaps in our knowledge, particularly with regards to xylem unloading and transport into heavily silicified cells. Silicification of tissues such as sclerenchyma, fibers, storage tissues, the epidermis, and vascular tissues are described. Silicon deposition in different cell types, tissues, and intercellular spaces that affect morphological and physiological properties associated with enhanced plant resilience under various biotic and abiotic stresses are addressed in detail. Most Si-derived benefits are the result of interference in physiological processes, modulation of stress responses, and biochemical interactions. A better understanding of the versatile roles of Si in plants requires more detailed knowledge of the specific mechanisms involved in its deposition in different tissues, at different developmental stages, and under different environmental conditions.

scholarly journals Coding of Non-coding RNA: Insights Into the Regulatory Functions of Pri-MicroRNA-Encoded Peptides in Plants

2021 ◽  
Vol 12 ◽  
Author(s):  
Yi Ren ◽  
Yue Song ◽  
Lipeng Zhang ◽  
Dinghan Guo ◽  
Juan He ◽  
...  
Keyword(s):  
Stress Responses ◽  
Messenger Rna ◽  
Molecular Mechanisms ◽  
Current Knowledge ◽  
Regulatory Peptides ◽  
Open Reading Frames ◽  
Circular Rnas ◽  
Signal Molecules ◽  
Long Distance ◽  
Functional Peptides

Peptides composed of a short chain of amino acids can play significant roles in plant growth, development, and stress responses. Most of these functional peptides are derived by either processing precursor proteins or direct translation of small open reading frames present in the genome and sometimes located in the untranslated region sequence of a messenger RNA. Generally, canonical peptides serve as local signal molecules mediating short- or long-distance intercellular communication. Also, they are commonly used as ligands perceived by an associated receptor, triggering cellular signaling transduction. In recent years, increasing pieces of evidence from studies in both plants and animals have revealed that peptides are also encoded by RNAs currently defined as non-coding RNAs (ncRNAs), including long ncRNAs, circular RNAs, and primary microRNAs. Primary microRNAs (miRNAs) have been reported to encode regulatory peptides in Arabidopsis, grapevine, soybean, and Medicago, called miRNA-encoded peptides (miPEPs). Remarkably, overexpression or exogenous applications of miPEPs specifically increase the expression level of their corresponding miRNAs by enhancing the transcription of the MIRNA (MIR) genes. Here, we first outline the current knowledge regarding the coding of putative ncRNAs. Notably, we review in detail the limited studies available regarding the translation of miPEPs and their relevant regulatory mechanisms. Furthermore, we discuss the potential cellular and molecular mechanisms in which miPEPs might be involved in plants and raise problems that needed to be solved.

scholarly journals Hypoxic and Thermal Stress: Many Ways Leading to the NOS/NO System in the Fish Heart

Antioxidants ◽  
2021 ◽  
Vol 10 (9) ◽  
pp. 1401
Author(s):  
Mariacristina Filice ◽  
Sandra Imbrogno ◽  
Alfonsina Gattuso ◽  
Maria Carmela Cerra
Keyword(s):  
Nitric Oxide ◽  
Stress Tolerance ◽  
Molecular Mechanisms ◽  
Environmental Changes ◽  
Current Knowledge ◽  
Blood Perfusion ◽  
Cardiac Cells ◽  
Adaptive Responses ◽  
Fish Heart ◽  
Temperature Regimes

Teleost fish are often regarded with interest for the remarkable ability of several species to tolerate even dramatic stresses, either internal or external, as in the case of fluctuations in O2 availability and temperature regimes. These events are naturally experienced by many fish species under different time scales, but they are now exacerbated by growing environmental changes. This further challenges the intrinsic ability of animals to cope with stress. The heart is crucial for the stress response, since a proper modulation of the cardiac function allows blood perfusion to the whole organism, particularly to respiratory organs and the brain. In cardiac cells, key signalling pathways are activated for maintaining molecular equilibrium, thus improving stress tolerance. In fish, the nitric oxide synthase (NOS)/nitric oxide (NO) system is fundamental for modulating the basal cardiac performance and is involved in the control of many adaptive responses to stress, including those related to variations in O2 and thermal regimes. In this review, we aim to illustrate, by integrating the classic and novel literature, the current knowledge on the NOS/NO system as a crucial component of the cardiac molecular mechanisms that sustain stress tolerance and adaptation, thus providing some species, such as tolerant cyprinids, with a high resistance to stress.

scholarly journals Degradation-Independent Inhibition of APOBEC3G by the HIV-1 Vif Protein

Viruses ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 617
Author(s):  
Benjamin Stupfler ◽  
Cédric Verriez ◽  
Sarah Gallois-Montbrun ◽  
Roland Marquet ◽  
Jean-Christophe Paillart
Keyword(s):  
Molecular Mechanisms ◽  
Viral Infections ◽  
Current Knowledge ◽  
Ubiquitin Proteasome System ◽  
Restriction Factors ◽  
Ubiquitin Ligase Complex ◽  
Ubiquitin Proteasome ◽  
Viral Infectivity Factor ◽  
Vif Protein ◽  
Hiv 1

The ubiquitin–proteasome system plays an important role in the cell under normal physiological conditions but also during viral infections. Indeed, many auxiliary proteins from the (HIV-1) divert this system to its own advantage, notably to induce the degradation of cellular restriction factors. For instance, the HIV-1 viral infectivity factor (Vif) has been shown to specifically counteract several cellular deaminases belonging to the apolipoprotein B mRNA-editing enzyme catalytic polypeptide-like (APOBEC3 or A3) family (A3A to A3H) by recruiting an E3-ubiquitin ligase complex and inducing their polyubiquitination and degradation through the proteasome. Although this pathway has been extensively characterized so far, Vif has also been shown to impede A3s through degradation-independent processes, but research on this matter remains limited. In this review, we describe our current knowledge regarding the degradation-independent inhibition of A3s, and A3G in particular, by the HIV-1 Vif protein, the molecular mechanisms involved, and highlight important properties of this small viral protein.

Mesophyll conductance: the leaf corridors for photosynthesis

2020 ◽  
Vol 48 (2) ◽  
pp. 429-439 ◽  
Author(s):  
Jorge Gago ◽  
Danilo M. Daloso ◽  
Marc Carriquí ◽  
Miquel Nadal ◽  
Melanie Morales ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Current Knowledge ◽  
Main Role ◽  
Mesophyll Conductance ◽  
Future Studies ◽  
Cell Structures ◽  
Leaf Tissues ◽  
Change Framework ◽  
Chloroplast Stroma

Besides stomata, the photosynthetic CO2 pathway also involves the transport of CO2 from the sub-stomatal air spaces inside to the carboxylation sites in the chloroplast stroma, where Rubisco is located. This pathway is far to be a simple and direct way, formed by series of consecutive barriers that the CO2 should cross to be finally assimilated in photosynthesis, known as the mesophyll conductance (gm). Therefore, the gm reflects the pathway through different air, water and biophysical barriers within the leaf tissues and cell structures. Currently, it is known that gm can impose the same level of limitation (or even higher depending of the conditions) to photosynthesis than the wider known stomata or biochemistry. In this mini-review, we are focused on each of the gm determinants to summarize the current knowledge on the mechanisms driving gm from anatomical to metabolic and biochemical perspectives. Special attention deserve the latest studies demonstrating the importance of the molecular mechanisms driving anatomical traits as cell wall and the chloroplast surface exposed to the mesophyll airspaces (Sc/S) that significantly constrain gm. However, even considering these recent discoveries, still is poorly understood the mechanisms about signaling pathways linking the environment a/biotic stressors with gm responses. Thus, considering the main role of gm as a major driver of the CO2 availability at the carboxylation sites, future studies into these aspects will help us to understand photosynthesis responses in a global change framework.

Alcohol Consumption and Risk of Uterine Fibroids

2020 ◽  
Vol 20 (4) ◽  
pp. 247-258 ◽  
Author(s):  
Hajra Takala ◽  
Qiwei Yang ◽  
Ahmed M. Abd El Razek ◽  
Mohamed Ali ◽  
Ayman Al-Hendy
Keyword(s):  
Alcohol Consumption ◽  
Animal Studies ◽  
Molecular Mechanisms ◽  
Legal Status ◽  
Current Knowledge ◽  
Uterine Fibroids ◽  
Future Directions ◽  
Working Adults ◽  
The Us ◽  
Alcohol Related Problems

Lifestyle factors, such as alcohol intake, have placed a substantial burden on public health. Alcohol consumption is increasing globally due to several factors including easy accessibility of this addictive substance besides its legal status and social acceptability. In the US, alcohol is the third leading preventable cause of death (after tobacco, poor diet and physical inactivity) with an estimated 88,000 people dying from alcohol-related causes annually, representing 1 in 10 deaths among working adults. Furthermore, the economic burden of excess drinking costs the US around $249 billion ($191.1 billion related to binge drinking). Although men likely drink more than women do, women are at much higher risk for alcohol-related problems. Alcohol use is also considered to be one of the most common non-communicable diseases, which affects reproductive health. This review article summarizes the current knowledge about alcohol-related pathogenesis of uterine fibroids (UFs) and highlights the molecular mechanisms that contribute to the development of UFs in response to alcohol consumption. Additionally, the effect of alcohol on the levels of various factors that are involved in UFs pathogenesis, such as steroid hormones, growth factors and cytokines, are summarized in this review. Animal studies of deleterious alcohol effect and future directions are discussed as well.

scholarly journals Molecular Mechanisms of Insulin Resistance in Polycystic Ovary Syndrome: Unraveling the Conundrum in Skeletal Muscle?

2019 ◽  
Vol 104 (11) ◽  
pp. 5372-5381 ◽  
Author(s):  
Nigel K Stepto ◽  
Alba Moreno-Asso ◽  
Luke C McIlvenna ◽  
Kirsty A Walters ◽  
Raymond J Rodgers
Keyword(s):  
Insulin Resistance ◽  
Skeletal Muscle ◽  
Polycystic Ovary Syndrome ◽  
Molecular Mechanisms ◽  
Current Knowledge ◽  
Polycystic Ovary ◽  
Evidence Synthesis ◽  
Basic Research ◽  
Future Research ◽  
Ovary Syndrome

Abstract Context Polycystic ovary syndrome (PCOS) is a common endocrine condition affecting 8% to 13% of women across the lifespan. PCOS affects reproductive, metabolic, and mental health, generating a considerable health burden. Advances in treatment of women with PCOS has been hampered by evolving diagnostic criteria and poor recognition by clinicians. This has resulted in limited clinical and basic research. In this study, we provide insights into the current and future research on the metabolic features of PCOS, specifically as they relate to PCOS-specific insulin resistance (IR), that may affect the most metabolically active tissue, skeletal muscle. Current Knowledge PCOS is a highly heritable condition, yet it is phenotypically heterogeneous in both reproductive and metabolic features. Human studies thus far have not identified molecular mechanisms of PCOS-specific IR in skeletal muscle. However, recent research has provided new insights that implicate energy-sensing pathways regulated via epigenomic and resultant transcriptomic changes. Animal models, while in existence, have been underused in exploring molecular mechanisms of IR in PCOS and specifically in skeletal muscle. Future Directions Based on the latest evidence synthesis and technologies, researchers exploring molecular mechanisms of IR in PCOS, specifically in muscle, will likely need to generate new hypothesis to be tested in human and animal studies. Conclusion Investigations to elucidate the molecular mechanisms driving IR in PCOS are in their early stages, yet remarkable advances have been made in skeletal muscle. Overall, investigations have thus far created more questions than answers, which provide new opportunities to study complex endocrine conditions.

scholarly journals Immune Actions on the Peripheral Nervous System in Pain

2021 ◽  
Vol 22 (3) ◽  
pp. 1448
Author(s):  
Jessica Aijia Liu ◽  
Jing Yu ◽  
Chi Wai Cheung
Keyword(s):  
Chronic Pain ◽  
Nervous System ◽  
Peripheral Nervous System ◽  
Immune Cells ◽  
Molecular Mechanisms ◽  
Process Integration ◽  
Current Knowledge ◽  
Therapeutic Strategies ◽  
Lipid Mediators ◽  
Cellular Changes

Pain can be induced by tissue injuries, diseases and infections. The interactions between the peripheral nervous system (PNS) and immune system are primary actions in pain sensitizations. In response to stimuli, nociceptors release various mediators from their terminals that potently activate and recruit immune cells, whereas infiltrated immune cells further promote sensitization of nociceptors and the transition from acute to chronic pain by producing cytokines, chemokines, lipid mediators and growth factors. Immune cells not only play roles in pain production but also contribute to PNS repair and pain resolution by secreting anti-inflammatory or analgesic effectors. Here, we discuss the distinct roles of four major types of immune cells (monocyte/macrophage, neutrophil, mast cell, and T cell) acting on the PNS during pain process. Integration of this current knowledge will enhance our understanding of cellular changes and molecular mechanisms underlying pain pathogenies, providing insights for developing new therapeutic strategies.

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