scholarly journals Cellular Stress and Molecular Responses in Bladder Ischemia

2021 ◽  
Vol 22 (21) ◽  
pp. 11862
Author(s):  
Jing-Hua Yang ◽  
Han-Pil Choi ◽  
Wanting Niu ◽  
Kazem M. Azadzoi
Keyword(s):  
Stress Response ◽  
Growth Factor ◽  
Detrusor Overactivity ◽  
Stress Responses ◽  
Cellular Stress ◽  
Detrusor Underactivity ◽  
Molecular Responses ◽  
Cellular Energy ◽  
Stress Sensors ◽  
Bladder Ischemia

The concept of bladder ischemia as a contributing factor to detrusor overactivity and lower urinary tract symptoms (LUTS) is evolving. Bladder ischemia as a consequence of pelvic arterial atherosclerosis was first documented in experimental models and later in elderly patients with LUTS. It was shown that early-stage moderate ischemia produces detrusor overactivity, while prolonged severe ischemia provokes changes consistent with detrusor underactivity. Recent studies imply a central role of cellular energy sensors, cellular stress sensors, and stress response molecules in bladder responses to ischemia. The cellular energy sensor adenosine monophosphate-activated protein kinase was shown to play a role in detrusor overactivity and neurodegeneration in bladder ischemia. The cellular stress sensors apoptosis signal-regulating kinase 1 and caspase-3 along with heat shock proteins were characterized as important contributing factors to smooth muscle structural modifications and apoptotic responses in bladder ischemia. Downstream pathways seem to involve hypoxia-inducible factor, transforming growth factor beta, vascular endothelial growth factor, and nerve growth factor. Molecular responses to bladder ischemia were associated with differential protein expression, the accumulation of non-coded amino acids, and post-translational modifications of contractile proteins and stress response molecules. Further insight into cellular stress responses in bladder ischemia may provide novel diagnostic and therapeutic targets against LUTS.

scholarly journals Flavonoids: Potential Candidates for the Treatment of Neurodegenerative Disorders

Biomedicines ◽  
2021 ◽  
Vol 9 (2) ◽  
pp. 99
Author(s):  
Shweta Devi ◽  
Vijay Kumar ◽  
Sandeep Kumar Singh ◽  
Ashish Kant Dubey ◽  
Jong-Joo Kim
Keyword(s):  
Stress Response ◽  
Stress Responses ◽  
Neurodegenerative Disorders ◽  
Cell Damage ◽  
Cellular Stress ◽  
Clinical Manifestations ◽  
Cellular Stress Response ◽  
Dramatic Rise ◽  
Cellular Stress Responses

Neurodegenerative disorders, such as Parkinson’s disease (PD), Alzheimer’s disease (AD), Amyotrophic lateral sclerosis (ALS), and Huntington’s disease (HD), are the most concerning disorders due to the lack of effective therapy and dramatic rise in affected cases. Although these disorders have diverse clinical manifestations, they all share a common cellular stress response. These cellular stress responses including neuroinflammation, oxidative stress, proteotoxicity, and endoplasmic reticulum (ER)-stress, which combats with stress conditions. Environmental stress/toxicity weakened the cellular stress response which results in cell damage. Small molecules, such as flavonoids, could reduce cellular stress and have gained much attention in recent years. Evidence has shown the potential use of flavonoids in several ways, such as antioxidants, anti-inflammatory, and anti-apoptotic, yet their mechanism is still elusive. This review provides an insight into the potential role of flavonoids against cellular stress response that prevent the pathogenesis of neurodegenerative disorders.

scholarly journals Stressors and Stress Responses in Cystic Fibrosis

2018 ◽  
Vol 5 (1) ◽  
pp. 11-29 ◽  
Author(s):  
Zsuzsa Bebok ◽  
Lianwu Fu
Keyword(s):  
Cystic Fibrosis ◽  
Stress Response ◽  
Stress Responses ◽  
Genetic Disorder ◽  
Cellular Stress ◽  
Cellular Stress Response ◽  
Bicarbonate Transport ◽  
Persistent Infections ◽  
Human Disorders ◽  
The Unfolded Protein Response

Abstract Cystic fibrosis (CF) is a life-shortening, genetic disorder caused by mutations in the cystic fibrosis transmembrane conductance regulator gene (CFTR). The primary cause of CF is reduced CFTR-mediated chloride and bicarbonate transport, due to mutations in CFTR. However, inflammation and persistent infections influence clinical outcome. Cellular stress response pathways, such as the unfolded protein response (UPR) and the integrated stress response (ISR), referred to here as cellular stress response pathways (SRPs), contribute to the pathology of human disorders. Multiple studies have indicated activation of SRPs in CF tissues. We review our present understanding of how SRPs are activated in CF and their contribution to pathology. We conclude that reduced CFTR function in CF organs establishes a tissue environment in which internal or external insults activate SRPs. SRPs contribute to CF pathogenesis by reducing CFTR expression, enhancing inflammation with consequent tissue remodeling. Understanding the contribution of SRPs to CF pathogenesis is crucial even in the era of CFTR “modulators” that are designed to potentiate, correct or amplify CFTR function, since there is an urgent need for supportive treatments. Importantly, CF patients with established pathology could benefit from the targeted use of drugs that modulate SRPs to reduce the symptoms.

scholarly journals Effect of Combined Stressors on C. elegans Lifespan

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. 667-667
Author(s):  
Bradford Hull ◽  
George Sutphin
Keyword(s):  
Heavy Metal ◽  
Stress Response ◽  
Stress Responses ◽  
Cellular Response ◽  
Multiple Stressors ◽  
Cellular Stress ◽  
Cellular Stress Response ◽  
C Elegans ◽  
Arsenic Copper ◽  
The Impact

Abstract Cellular stress is a fundamental component of age-associated disease. Cells experience many forms of stress (oxidative, heavy metal, etc.), and as we age the burden of stress and resulting damage increases while our cells’ ability to deal with the consequences becomes diminished due to dysregulation of cellular stress response pathways. By understanding how cells respond to stress we aim to slow age-associated deterioration and develop treatment targets for age-associated disease. The majority of past work has focused on understanding responses to individual stressors. In contrast, how pathology and stress responses differ in the presence of multiple stressors is relatively unknown; we investigate that here. We cultured worms on agar plates with different combinations of arsenic, copper, and DTT (which create oxidative/proteotoxic, heavy metal, and endoplasmic reticulum (ER) stress, respectively) at doses that result in 20% lifespan reduction individually and measured the effect on lifespan. We found that arsenic/copper and arsenic/DTT combinations created additive lifespan reductions while the copper/DTT combination created an antagonistic lifespan reduction when compared to controls (p<0.05). This antagonistic toxicity suggests an interaction either between the mechanisms of toxicity or the cellular response to copper and DTT. We are now evaluating the impact of copper and DTT individually and in combination on unfolded protein and heavy metal response pathways to understand the underlying mechanism of the interaction. Additionally, we are continuing to screen stressors to identify combinations that cause non-additive (synergistic or antagonistic) toxicity to build a comprehensive model of the genetic stress response network in C. elegans.

scholarly journals Evidence of the Cellular Senescence Stress Response in Mitotically Active Brain Cells—Implications for Cancer and Neurodegeneration

Life ◽  
2021 ◽  
Vol 11 (2) ◽  
pp. 153
Author(s):  
Gregory J. Gillispie ◽  
Eric Sah ◽  
Sudarshan Krishnamurthy ◽  
Mohamed Y. Ahmidouch ◽  
Bin Zhang ◽  
...  
Keyword(s):  
Stress Response ◽  
Neurodegenerative Diseases ◽  
Cell Fate ◽  
Cellular Senescence ◽  
Stress Responses ◽  
Cellular Stress ◽  
Surrounding Tissue ◽  
Brain Cells ◽  
Cell Fate Decisions ◽  
The Brain

Cellular stress responses influence cell fate decisions. Apoptosis and proliferation represent opposing reactions to cellular stress or damage and may influence distinct health outcomes. Clinical and epidemiological studies consistently report inverse comorbidities between age-associated neurodegenerative diseases and cancer. This review discusses how one particular stress response, cellular senescence, may contribute to this inverse correlation. In mitotically competent cells, senescence is favorable over uncontrolled proliferation, i.e., cancer. However, senescent cells notoriously secrete deleterious molecules that drive disease, dysfunction and degeneration in surrounding tissue. In recent years, senescent cells have emerged as unexpected mediators of neurodegenerative diseases. The present review uses pre-defined criteria to evaluate evidence of cellular senescence in mitotically competent brain cells, highlights the discovery of novel molecular regulators and discusses how this single cell fate decision impacts cancer and degeneration in the brain. We also underscore methodological considerations required to appropriately evaluate the cellular senescence stress response in the brain.

scholarly journals FOXO3a from the Nucleus to the Mitochondria: A Round Trip in Cellular Stress Response

Cells ◽  
2019 ◽  
Vol 8 (9) ◽  
pp. 1110 ◽  
Author(s):  
Candida Fasano ◽  
Vittoria Disciglio ◽  
Stefania Bertora ◽  
Martina Lepore Signorile ◽  
Cristiano Simone
Keyword(s):  
Stress Response ◽  
Protein Kinase ◽  
Stress Responses ◽  
Target Genes ◽  
Cellular Stress ◽  
Genotoxic Stress ◽  
Cellular Stress Response ◽  
Mitogen Activated Protein Kinase ◽  
Mitochondrial Functions ◽  
Stressed Cells

Cellular stress response is a universal mechanism that ensures the survival or negative selection of cells in challenging conditions. The transcription factor Forkhead box protein O3 (FOXO3a) is a core regulator of cellular homeostasis, stress response, and longevity since it can modulate a variety of stress responses upon nutrient shortage, oxidative stress, hypoxia, heat shock, and DNA damage. FOXO3a activity is regulated by post-translational modifications that drive its shuttling between different cellular compartments, thereby determining its inactivation (cytoplasm) or activation (nucleus and mitochondria). Depending on the stress stimulus and subcellular context, activated FOXO3a can induce specific sets of nuclear genes, including cell cycle inhibitors, pro-apoptotic genes, reactive oxygen species (ROS) scavengers, autophagy effectors, gluconeogenic enzymes, and others. On the other hand, upon glucose restriction, 5′-AMP-activated protein kinase (AMPK) and mitogen activated protein kinase kinase (MEK)/extracellular signal-regulated kinase (ERK) -dependent FOXO3a mitochondrial translocation allows the transcription of oxidative phosphorylation (OXPHOS) genes, restoring cellular ATP levels, while in cancer cells, mitochondrial FOXO3a mediates survival upon genotoxic stress induced by chemotherapy. Interestingly, these target genes and their related pathways are diverse and sometimes antagonistic, suggesting that FOXO3a is an adaptable player in the dynamic homeostasis of normal and stressed cells. In this review, we describe the multiple roles of FOXO3a in cellular stress response, with a focus on both its nuclear and mitochondrial functions.

scholarly journals The mammalian decidual cell evolved from a cellular stress response

2018 ◽  
Author(s):  
Eric M. Erkenbrack ◽  
Jamie D. Maziarz ◽  
Oliver W. Griffith ◽  
Cong Liang ◽  
Arun R. Chavan ◽  
...  
Keyword(s):  
Stress Response ◽  
Stress Responses ◽  
Molecular Mechanisms ◽  
Cellular Stress ◽  
Cell Types ◽  
Monodelphis Domestica ◽  
Cellular Stress Response ◽  
General Mechanism ◽  
Decidual Cell ◽  
Cell Type

AbstractAmong animal species, cell types vary greatly in terms of number and kind. The broad range of number of cell types among species suggests that cell type origination is a significant source of evolutionary novelty. The molecular mechanisms giving rise to novel cell types, however, are poorly understood. Here we show that a novel cell type of eutherian mammals, the decidual stromal cell (DSC), evolved by rewiring an ancestral cellular stress response. We isolated the precursor cell type of DSCs, endometrial stromal fibroblasts (ESFs), from the opossum Monodelphis domestica. We show that, in opossum ESF, the majority of decidual core regulatory genes respond to decidualizing signals, but do not regulate decidual effector genes. Rather, in opossum ESF, decidual transcription factors function in apoptotic and oxidative stress response. We propose that the rewiring of cellular stress responses could be a general mechanism for the evolution of novel cell types.

Inhibition of Nonsense Mediated RNA Decay in Hypoxic Cells; Implications for Thalassemia.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 1781-1781
Author(s):  
Lawrence B. Gardner
Keyword(s):  
Stress Response ◽  
Stress Responses ◽  
Cellular Response ◽  
Globin Gene ◽  
Cellular Stress ◽  
Regulation Of Gene Expression ◽  
Cellular Stress Response ◽  
Rna Decay ◽  
Processing Bodies ◽  
Nonsense Mediated Rna Decay

Abstract Several common β globin gene mutations found in thalassemia are thought to promote rapid degradation of the aberrant mRNA through a specific mechanism termed nonsense mediated RNA decay (NMD). NMD, elicited through mutations leading to premature termination codons, is thought to be responsible not only for the degradation of the β globin PTC 39 mutation, responsible for >90% of thalassemia in Sardinia, but also for the degradation of 30% of all known human mutations and up to 10% of the genome. However, because NMD has been thought of as a constitutive and not a regulated pathway, the potential role of NMD in the dynamic regulation of gene expression has not been well explored. We have determined that NMD is inhibited in hypoxic cells. This hypoxic inhibition of NMD significantly prolongs the half-life of multiple mRNAs degraded by NMD, including the β globin PTC 39 mutation. We have also identified several additional mRNAs whose stabilities are significantly (>2 fold) 1. Increased when Rent1, an RNA helicase necessary for NMD is silenced 2. Decreased when Rent1 is over-expressed and 3. Increased in hypoxic cells when NMD is inhibited. These include the mRNAs that are integral for the cellular response to multiple stresses found in thalassemia, including hypoxic stress. Indeed, we observed that the cellular stress response is augmented when NMD is inhibited. The central component for many cellular stress responses is the phosphorylation of a translation factor, eIF2α. We and others have demonstrated that eIF2α is phosphorylated in hypoxic cells via the kinase PERK. Phosphorylation of eIF2α leads to the suppression of protein synthesis and the translational and transcriptional up-regulation of stress response genes. We hypothesized that phosphorylation of eIF2α was also responsible for the hypoxic inhibition of NMD. Indeed, when we used cells generated from mice in which wild-type eIF2α has been replaced by an eIF2α that cannot be phosphorylated, we found that hypoxic inhibition of NMD did not occur, demonstrating that is eIF2α phosphorylation is necessary for hypoxic inhibition of NMD. Degradation of NMD targets occurs in cytoplasmic processing bodies, which contain many of the enzymes necessary for mRNA catabolism. We noted that a distinct type of mRNA containing body, termed stress bodies, which do not have the capacity for RNA decay, are induced in hypoxic cells. This formation is dependent on PERK phosphorylation of eIF2α. While there are several potential mechanism by which hypoxic phosphorylation of eIF2α could inhibit NMD, our preliminary data suggests a model in which NMD targets are sequestered in cytoplasmic stress granules in hypoxic cells, thus excluding them from cytoplasmic processing bodies. Thus our studies reveal a novel form of gene regulation in hypoxic cells, regulation of NMD via phosphorylation of eIF2α. This finding has potential significance in many disease states, but particularly in thalassemia, where many of the stresses which phosphorylate eIF2α occur, and where the stress response and regulation of mutated β globin mRNAs may be particularly important.

Sign in / Sign up

Export Citation Format

Share Document