scholarly journals Jack GD, Mead EA, Garst JF, Cabrera MC, DeSantis, AM, Slaughter SM, Jervis J, Brooks AI, Potts M, Helm RF. Long term metabolic arrest and recovery of HEK293 spheroids involves NF-κB signaling and sustained JNK activation,Journal of Cellular Physiology (2006) 206(2) 526–536

2006 ◽  
Vol 209 (3) ◽  
pp. 1055-1055
Keyword(s):  
Cellular Physiology ◽  
Metabolic Arrest ◽  
Jnk Activation

Long term metabolic arrest and recovery of HEK293 spheroids involves NF-κB signaling and sustained JNK activation

2006 ◽  
Vol 206 (2) ◽  
pp. 526-536 ◽  
Author(s):  
Graham D. Jack ◽  
E. Andrew Mead ◽  
James F. Garst ◽  
M. Carla Cabrera ◽  
Andrea M. DeSantis ◽  
...  
Keyword(s):  
Metabolic Arrest ◽  
Jnk Activation

scholarly journals Increasing intracellular trehalose is sufficient to confer desiccation tolerance toSaccharomyces cerevisiae

2015 ◽  
Vol 112 (19) ◽  
pp. 6122-6127 ◽  
Author(s):  
Hugo Tapia ◽  
Lindsey Young ◽  
Douglas Fox ◽  
Carolyn R. Bertozzi ◽  
Douglas Koshland
Keyword(s):  
Desiccation Tolerance ◽  
Protein Misfolding ◽  
De Novo ◽  
Metabolic Effects ◽  
The Media ◽  
Metabolic Arrest ◽  
Induced Tolerance ◽  
High Level ◽  
Protein Misfolding And Aggregation

Diverse organisms capable of surviving desiccation, termed anhydrobiotes, include species from bacteria, yeast, plants, and invertebrates. However, most organisms are sensitive to desiccation, likely due to an assortment of different stresses such as protein misfolding and aggregation, hyperosmotic stress, membrane fracturing, and changes in cell volume and shape leading to an overcrowded cytoplasm and metabolic arrest. The exact stress(es) that cause lethality in desiccation-sensitive organisms and how the lethal stresses are mitigated in desiccation-tolerant organisms remain poorly understood. The presence of trehalose in anhydrobiotes has been strongly correlated with desiccation tolerance. In the yeastSaccharomyces cerevisiae, trehalose is essential for survival after long-term desiccation. Here, we establish that the elevation of intracellular trehalose in dividing yeast by its import from the media converts yeast from extreme desiccation sensitivity to a high level of desiccation tolerance. This trehalose-induced tolerance is independent of utilization of trehalose as an energy source, de novo synthesis of other stress effectors, or the metabolic effects of trehalose biosynthetic intermediates, indicating that a chemical property of trehalose is directly responsible for desiccation tolerance. Finally, we demonstrate that elevated intracellular maltose can also make dividing yeast tolerant to short-term desiccation, indicating that other disaccharides have stress effector activity. However, trehalose is much more effective than maltose at conferring tolerance to long-term desiccation. The effectiveness and sufficiency of trehalose as an antagonizer of desiccation-induced damage in yeast emphasizes its potential to confer desiccation tolerance to otherwise sensitive organisms.

Is long-term hypoxia met by the Pasteur effect in roots of wheat seedlings?

1994 ◽  
Vol 102 ◽  
pp. 407-412 ◽  
Author(s):  
G. Albrecht ◽  
E.-M. Wiedenroth
Keyword(s):  
Hypoxia Tolerance ◽  
Soluble Carbohydrates ◽  
Low Oxygen ◽  
Wheat Roots ◽  
Wheat Seedlings ◽  
Pasteur Effect ◽  
Metabolic Arrest ◽  
Oxygen Shortage ◽  
Anaerobic Environment

SynopsisIt has been argued, whether or not the Pasteur effect occurs in plant tissues as a response to long-term hypoxia. To study this question roots of wheat seedlings (Triticum aestivum L. cv. Alcedo) were analysed following acclimation to oxygen shortage by a prior 6-d-cultivation in a nitrogen-flushed nutrient solution. A Pasteur Quotient of approximately one suggested the absence of a significant Pasteur effect. This conclusion was supported by finding an accumulation of soluble carbohydrates.A progressive adaptation of hypoxically pretreated wheat roots was indicated by measurements under low oxygen tension of 2 kPa, when half of the produced carbon dioxide was generated by fermentation (Gas exchange Quotient, GQ≈2.1) with no apparent increase in the glycolytic substrate flux. The remaining oxygen uptake was even higher in hypoxically grown roots than in the aerobically grown control specimens. When whole seedlings were placed in oxygen-free conditions for 2 h, roots of seedlings pretreated hypoxically suffered a 50% loss in the concentration of ATP, while 90% of the ATP was lost in roots transferred from an aerated solution directly into an anaerobic environment. This was interpreted as an improvement in hypoxia tolerance by minimising the fermentation rate (low PQ) but in particular the ATP requirements by metabolic arrest strategies.

scholarly journals Protein-Damaging Stresses Activate c-Jun N-Terminal Kinase via Inhibition of Its Dephosphorylation: a Novel Pathway Controlled by HSP72

1999 ◽  
Vol 19 (4) ◽  
pp. 2547-2555 ◽  
Author(s):  
Anatoli B. Meriin ◽  
Julia A. Yaglom ◽  
Vladimir L. Gabai ◽  
Dick D. Mosser ◽  
Leonard Zon ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Heat Shock ◽  
Uv Irradiation ◽  
Osmotic Shock ◽  
Interleukin 1 ◽  
P38 Kinase ◽  
Cellular Physiology ◽  
Jnk Activation ◽  
And Oxidative Stress ◽  
Stimulation Of

ABSTRACT Various stresses activate the c-Jun N-terminal kinase (JNK), which is involved in the regulation of many aspects of cellular physiology, including apoptosis. Here we demonstrate that in contrast to UV irradiation, heat shock causes little or no stimulation of the JNK-activating kinase SEK1, while knocking out the SEK1gene completely blocks heat-induced JNK activation. Therefore, we tested whether heat shock activates JNK via inhibition of JNK dephosphorylation. The rate of JNK dephosphorylation in unstimulated cells was high, and exposure to UV irradiation, osmotic shock, interleukin-1, or anisomycin did not affect this process. Conversely, exposure of cells to heat shock and other protein-damaging conditions, including ethanol, arsenite, and oxidative stress, strongly reduced the rate of JNK dephosphorylation. Under these conditions, we did not observe any effects on dephosphorylation of the homologous p38 kinase, suggesting that suppression of dephosphorylation is specific to JNK. Together, these data indicate that activation of JNK by protein-damaging treatments is mediated primarily by inhibition of a JNK phosphatase(s). Elevation of cellular levels of the major heat shock protein Hsp72 inhibited a repression of JNK dephosphorylation by these stressful treatments, which explains recent reports of the suppression of JNK activation by Hsp72.

scholarly journals Selective Proteomic Analysis of Antibiotic-Tolerant Cellular Subpopulations in Pseudomonas aeruginosa Biofilms

mBio ◽  
2017 ◽  
Vol 8 (5) ◽  
Author(s):  
Brett M. Babin ◽  
Lydia Atangcho ◽  
Mark B. van Eldijk ◽  
Michael J. Sweredoski ◽  
Annie Moradian ◽  
...  
Keyword(s):  
Proteomic Analysis ◽  
Chemical Biology ◽  
Initial Response ◽  
Adaptive Strategy ◽  
Cell Level ◽  
Cellular Physiology ◽  
Proteomic Response ◽  
Behavioral Heterogeneity ◽  
Pathogenic Biofilms

ABSTRACT Biofilm infections exhibit high tolerance against antibiotic treatment. The study of biofilms is complicated by phenotypic heterogeneity; biofilm subpopulations differ in their metabolic activities and their responses to antibiotics. Here, we describe the use of the bio-orthogonal noncanonical amino acid tagging (BONCAT) method to enable selective proteomic analysis of a Pseudomonas aeruginosa biofilm subpopulation. Through controlled expression of a mutant methionyl-tRNA synthetase, we targeted BONCAT labeling to cells in the regions of biofilm microcolonies that showed increased tolerance to antibiotics. We enriched and identified proteins synthesized by cells in these regions. Compared to the entire biofilm proteome, the labeled subpopulation was characterized by a lower abundance of ribosomal proteins and was enriched in proteins of unknown function. We performed a pulse-labeling experiment to determine the dynamic proteomic response of the tolerant subpopulation to supra-MIC treatment with the fluoroquinolone antibiotic ciprofloxacin. The adaptive response included the upregulation of proteins required for sensing and repairing DNA damage and substantial changes in the expression of enzymes involved in central carbon metabolism. We differentiated the immediate proteomic response, characterized by an increase in flagellar motility, from the long-term adaptive strategy, which included the upregulation of purine synthesis. This targeted, selective analysis of a bacterial subpopulation demonstrates how the study of proteome dynamics can enhance our understanding of biofilm heterogeneity and antibiotic tolerance. IMPORTANCE Bacterial growth is frequently characterized by behavioral heterogeneity at the single-cell level. Heterogeneity is especially evident in the physiology of biofilms, in which distinct cellular subpopulations can respond differently to stresses, including subpopulations of pathogenic biofilms that are more tolerant to antibiotics. Global proteomic analysis affords insights into cellular physiology but cannot identify proteins expressed in a particular subpopulation of interest. Here, we report a chemical biology method to selectively label, enrich, and identify proteins expressed by cells within distinct regions of biofilm microcolonies. We used this approach to study changes in protein synthesis by the subpopulation of antibiotic-tolerant cells throughout a course of treatment. We found substantial differences between the initial response and the long-term adaptive strategy that biofilm cells use to cope with antibiotic stress. The method we describe is readily applicable to investigations of bacterial heterogeneity in diverse contexts. IMPORTANCE Bacterial growth is frequently characterized by behavioral heterogeneity at the single-cell level. Heterogeneity is especially evident in the physiology of biofilms, in which distinct cellular subpopulations can respond differently to stresses, including subpopulations of pathogenic biofilms that are more tolerant to antibiotics. Global proteomic analysis affords insights into cellular physiology but cannot identify proteins expressed in a particular subpopulation of interest. Here, we report a chemical biology method to selectively label, enrich, and identify proteins expressed by cells within distinct regions of biofilm microcolonies. We used this approach to study changes in protein synthesis by the subpopulation of antibiotic-tolerant cells throughout a course of treatment. We found substantial differences between the initial response and the long-term adaptive strategy that biofilm cells use to cope with antibiotic stress. The method we describe is readily applicable to investigations of bacterial heterogeneity in diverse contexts.

scholarly journals Interleukin-4 Synergizes With Raf-1 to Promote Long-Term Proliferation and Activation of c-jun N-terminal Kinase

Blood ◽  
1999 ◽  
Vol 93 (11) ◽  
pp. 3694-3702 ◽  
Author(s):  
Megan K. Levings ◽  
Darrell C. Bessette ◽  
John W. Schrader
Keyword(s):  
Protein Kinase ◽  
Cellular Growth ◽  
Mitogen Activated Protein Kinase ◽  
Interleukin 4 ◽  
Extracellular Signal ◽  
Mitogen Activated Protein ◽  
Jnk Activation ◽  
Erk Activity ◽  
Increased Activity

Abstract This report shows that interleukin-4 (IL-4), which plays a key role in regulating immune responses, fails to support cellular growth. We investigated whether this failure of IL-4 to promote growth was because of its unique inability to activate the Ras/Raf/Erk pathway. Consistent with other reports, expression in Ba/F3, a factor-dependent hematopoietic cell line, of either activated Q61KN-Ras or a hormone-inducible activated Raf-1, resulted in suppression of apoptosis but not in long-term growth. However, in the presence of IL-4, Ba/F3 cells that expressed either Q61KN-Ras or activated Raf-1 grew continuously at a rate comparable with that stimulated by IL-3. Investigation of the biochemical events associated with the stimulation of long-term growth showed that, as expected, the presence of activated Raf-1 resulted in an increased activity of extracellular signal regulated kinase (ERK) mitogen-activated protein kinase (MAPK) but not of c-jun N-terminal kinase/stress-activated protein kinase (JNK). However, surprisingly, if IL-4 was present, cells expressing active Raf-1 exhibited increases in JNK activity. These observations point to a novel mechanism for JNK activation involving synergy between Raf-1 and pathways activated by IL-4 and suggest that in hematopoietic cells proliferation is correlated not only with “mitogen activated” ERK activity, but also with JNK activity.

scholarly journals Interleukin-4 Synergizes With Raf-1 to Promote Long-Term Proliferation and Activation of c-jun N-terminal Kinase

Blood ◽  
1999 ◽  
Vol 93 (11) ◽  
pp. 3694-3702 ◽  
Author(s):  
Megan K. Levings ◽  
Darrell C. Bessette ◽  
John W. Schrader
Keyword(s):  
Protein Kinase ◽  
Cellular Growth ◽  
Mitogen Activated Protein Kinase ◽  
Interleukin 4 ◽  
Extracellular Signal ◽  
Mitogen Activated Protein ◽  
Jnk Activation ◽  
Erk Activity ◽  
Increased Activity

This report shows that interleukin-4 (IL-4), which plays a key role in regulating immune responses, fails to support cellular growth. We investigated whether this failure of IL-4 to promote growth was because of its unique inability to activate the Ras/Raf/Erk pathway. Consistent with other reports, expression in Ba/F3, a factor-dependent hematopoietic cell line, of either activated Q61KN-Ras or a hormone-inducible activated Raf-1, resulted in suppression of apoptosis but not in long-term growth. However, in the presence of IL-4, Ba/F3 cells that expressed either Q61KN-Ras or activated Raf-1 grew continuously at a rate comparable with that stimulated by IL-3. Investigation of the biochemical events associated with the stimulation of long-term growth showed that, as expected, the presence of activated Raf-1 resulted in an increased activity of extracellular signal regulated kinase (ERK) mitogen-activated protein kinase (MAPK) but not of c-jun N-terminal kinase/stress-activated protein kinase (JNK). However, surprisingly, if IL-4 was present, cells expressing active Raf-1 exhibited increases in JNK activity. These observations point to a novel mechanism for JNK activation involving synergy between Raf-1 and pathways activated by IL-4 and suggest that in hematopoietic cells proliferation is correlated not only with “mitogen activated” ERK activity, but also with JNK activity.

Therapy and prevention for mental health: What if mental diseases are mostly not brain disorders?

2019 ◽  
Vol 42 ◽  
Author(s):  
John P. A. Ioannidis
Keyword(s):  
Mental Health ◽  
Mental Disease ◽  
Brain Disorders ◽  
Social Stressors ◽  
Labor Education ◽  
Mental Diseases ◽  
Long Term Follow Up ◽  
Political Decisions

AbstractNeurobiology-based interventions for mental diseases and searches for useful biomarkers of treatment response have largely failed. Clinical trials should assess interventions related to environmental and social stressors, with long-term follow-up; social rather than biological endpoints; personalized outcomes; and suitable cluster, adaptive, and n-of-1 designs. Labor, education, financial, and other social/political decisions should be evaluated for their impacts on mental disease.

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