scholarly journals Tissue-specific modulation of gene expression in response to lowered insulin signalling in Drosophila

eLife ◽  
2021 ◽  
Vol 10 ◽  
Author(s):  
Luke Stephen Tain ◽  
Robert Sehlke ◽  
Ralf Leslie Meilenbrock ◽  
Thomas Leech ◽  
Jonathan Paulitz ◽  
...  
Keyword(s):  
Dna Damage ◽  
Fat Body ◽  
Insulin Signalling ◽  
Health Improvement ◽  
Proteomic Profiling ◽  
Protein Subunit ◽  
Altered Expression ◽  
Tissue Specific ◽  
Age Related ◽  
Specific Regulation

Reduced activity of the insulin/IGF signalling network increases health during ageing in multiple species. Diverse and tissue-specific mechanisms drive the health improvement. Here, we performed tissue-specific transcriptional and proteomic profiling of long-lived Drosophila dilp2-3,5 mutants, and identified tissue-specific regulation of >3600 transcripts and >3700 proteins. Most expression changes were regulated post-transcriptionally in the fat body, and only in mutants infected with the endosymbiotic bacteria, Wolbachia pipientis, which increases their lifespan. Bioinformatic analysis identified reduced co-translational ER targeting of secreted and membrane-associated proteins and increased DNA damage/repair response proteins. Accordingly, age-related DNA damage and genome instability were lower in fat body of the mutant, and overexpression of a minichromosome maintenance protein subunit extended lifespan. Proteins involved in carbohydrate metabolism showed altered expression in the mutant intestine, and gut-specific overexpression of a lysosomal mannosidase increased autophagy, gut homeostasis, and lifespan. These processes are candidates for combatting ageing-related decline in other organisms.

scholarly journals Tissue-specific transcriptional patterns underlie seasonal phenotypes in honey bees (Apis mellifera)

2021 ◽  
Author(s):  
Sean Bresnahan ◽  
Mehmet Döke ◽  
Tugrul Giray ◽  
Christina Grozinger
Keyword(s):  
Apis Mellifera ◽  
Honey Bees ◽  
Flight Muscle ◽  
Fat Body ◽  
Expression Patterns ◽  
Flight Activity ◽  
Insect Species ◽  
Tissue Specific ◽  
Transcriptional Profiles ◽  
Specific Regulation

Faced with adverse conditions, such as winter in temperate regions or hot and dry conditions in tropical regions, many insect species enter a state of diapause, a period of dormancy associated with a reduction or arrest of physical activity, development, and reproduction. Changes in common physiological pathways underlie diapause phenotypes in different insect species. However, most transcriptomic studies of diapause have not simultaneously evaluated and compared expression patterns in different tissues. Honey bees (Apis mellifera) represent a unique model system to study the mechanisms underpinning diapause. In winter, honey bees exhibit a classic diapause phenotype, with reduced metabolic activity, increased physiological nutritional resources, and altered hormonal profiles. However, winter bees actively heat their colony by vibrating their wing muscles; thus, this tissue is not quiescent. Here, we evaluated the transcriptional profiles of flight muscle tissue and fat body tissue (involved in nutrient storage, metabolism and immune function) of winter bees. We also evaluated two behavioral phenotypes of summer bees: nurses, which exhibit high nutritional stores and low flight activity, and foragers, which exhibit low nutritional stores and high flight activity. We found winter bees and nurses have similar fat body transcriptional profiles compared to foragers, whereas winter bees and foragers have similar flight muscle transcriptional profiles compared to nurses. Additionally, differentially expressed genes were enriched in diapause-related GO terms. Thus, honey bees exhibit tissue-specific transcriptional profiles associated with diapause, laying the groundwork for future studies evaluating the mechanisms, evolution, and consequences of this tissue-specific regulation.

scholarly journals Perturbed DNA methylation by sustained overexpression of Gadd45b induces chromatin disorganization, DNA strand breaks and dopaminergic neuron death in mice

2020 ◽  
Author(s):  
Camille Ravel-Godreuil ◽  
Olivia Massiani-Beaudoin ◽  
Philippe Mailly ◽  
Alain Prochiantz ◽  
Rajiv L. Joshi ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Dna Damage ◽  
Parkinson Disease ◽  
Dopaminergic Neuron ◽  
Dna Demethylation ◽  
Neuron Death ◽  
Neuron Degeneration ◽  
Altered Expression ◽  
Active Dna Demethylation ◽  
Age Related

AbstractHeterochromatin disorganization is a key hallmark of aging and DNA methylation state is currently the main molecular predictor of chronological age. The most frequent neurodegenerative diseases like Parkinson disease and Alzheimer’s disease are age-related but how the aging process and chromatin alterations are linked to neurodegeneration is unknown. Here, we investigated the consequences of viral overexpression of Gadd45b, a multifactorial protein involved in active DNA demethylation, in the midbrain of wild-type mice. Gadd45b overexpression induces global and stable changes in DNA methylation, particularly on gene bodies of genes related to neuronal functions. DNA methylation changes were accompanied by perturbed H3K9me3-marked heterochromatin and increased DNA damage. Prolonged Gadd45b expression resulted in dopaminergic neuron degeneration accompanied by altered expression of candidate genes related to heterochromatin maintenance, DNA methylation or Parkinson disease. Gadd45b overexpression rendered midbrain dopaminergic neurons more vulnerable to acute oxidative stress. Heterochromatin disorganization and DNA demethylation resulted in derepression of mostly young LINE-1 transposable elements, a potential source of DNA damage, prior to Gadd45b-induced neurodegeneration. Our data implicate that alterations in DNA methylation and heterochromatin organization, LINE-1 derepression and DNA damage can represent important contributors in the pathogenic mechanisms of dopaminergic neuron degeneration with potential implications for Parkinson disease.

scholarly journals DNA Damage-Induced Inflammatory Microenvironment and Adult Stem Cell Response

2021 ◽  
Vol 9 ◽  
Author(s):  
Davide Cinat ◽  
Robert P. Coppes ◽  
Lara Barazzuol
Keyword(s):  
Stem Cells ◽  
Dna Damage ◽  
Stem Cell ◽  
Adult Stem Cells ◽  
Genotoxic Stress ◽  
Inflammatory Factors ◽  
Functional Requirements ◽  
Tissue Specific ◽  
Inflammatory Microenvironment ◽  
Age Related

Adult stem cells ensure tissue homeostasis and regeneration after injury. Due to their longevity and functional requirements, throughout their life stem cells are subject to a significant amount of DNA damage. Genotoxic stress has recently been shown to trigger a cascade of cell- and non-cell autonomous inflammatory signaling pathways, leading to the release of pro-inflammatory factors and an increase in the amount of infiltrating immune cells. In this review, we discuss recent evidence of how DNA damage by affecting the microenvironment of stem cells present in adult tissues and neoplasms can affect their maintenance and long-term function. We first focus on the importance of self-DNA sensing in immunity activation, inflammation and secretion of pro-inflammatory factors mediated by activation of the cGAS-STING pathway, the ZBP1 pathogen sensor, the AIM2 and NLRP3 inflammasomes. Alongside cytosolic DNA, the emerging roles of cytosolic double-stranded RNA and mitochondrial DNA are discussed. The DNA damage response can also initiate mechanisms to limit division of damaged stem/progenitor cells by inducing a permanent state of cell cycle arrest, known as senescence. Persistent DNA damage triggers senescent cells to secrete senescence-associated secretory phenotype (SASP) factors, which can act as strong immune modulators. Altogether these DNA damage-mediated immunomodulatory responses have been shown to affect the homeostasis of tissue-specific stem cells leading to degenerative conditions. Conversely, the release of specific cytokines can also positively impact tissue-specific stem cell plasticity and regeneration in addition to enhancing the activity of cancer stem cells thereby driving tumor progression. Further mechanistic understanding of the DNA damage-induced immunomodulatory response on the stem cell microenvironment might shed light on age-related diseases and cancer, and potentially inform novel treatment strategies.

scholarly journals Tissue-specific transcriptional patterns underlie seasonal phenotypes in honey bees (Apis mellifera)

2021 ◽  
Author(s):  
Sean Bresnahan ◽  
Mehmet Döke ◽  
Tugrul Giray ◽  
Christina Grozinger
Keyword(s):  
Apis Mellifera ◽  
Honey Bees ◽  
Flight Muscle ◽  
Fat Body ◽  
Expression Patterns ◽  
Flight Activity ◽  
Insect Species ◽  
Tissue Specific ◽  
Transcriptional Profiles ◽  
Specific Regulation

Faced with adverse conditions, such as winter in temperate regions or hot and dry conditions in tropical regions, many insect species enter a state of diapause, a period of dormancy associated with a reduction or arrest of physical activity, development, and reproduction. Changes in common physiological pathways underlie diapause phenotypes in different insect species. However, most transcriptomic studies of diapause have not simultaneously evaluated and compared expression patterns in different tissues. Honey bees (Apis mellifera) represent a unique model system to study the mechanisms underpinning diapause. In winter, honey bees exhibit a classic diapause phenotype, with reduced metabolic activity, increased physiological nutritional resources, and altered hormonal profiles. However, winter bees actively heat their colony by vibrating their wing muscles; thus, this tissue is not quiescent. Here, we evaluated the transcriptional profiles of flight muscle tissue and fat body tissue (involved in nutrient storage, metabolism and immune function) of winter bees. We also evaluated two behavioral phenotypes of summer bees: nurses, which exhibit high nutritional stores and low flight activity, and foragers, which exhibit low nutritional stores and high flight activity. We found winter bees and nurses have similar fat body transcriptional profiles compared to foragers, whereas winter bees and foragers have similar flight muscle transcriptional profiles compared to nurses. Additionally, differentially expressed genes were enriched in diapause-related GO terms. Thus, honey bees exhibit tissue-specific transcriptional profiles associated with diapause, laying the groundwork for future studies evaluating the mechanisms, evolution, and consequences of this tissue-specific regulation.

Oxidative Stress, Ocular Disease and Diabetes Retinopathy

2019 ◽  
Vol 24 (40) ◽  
pp. 4726-4741 ◽  
Author(s):  
Orathai Tangvarasittichai ◽  
Surapon Tangvarasittichai
Keyword(s):  
Oxidative Stress ◽  
Dna Damage ◽  
Cell Death ◽  
Protein Modification ◽  
Morphological Changes ◽  
Corneal Dystrophy ◽  
Age Related Macular Degeneration ◽  
Ocular Diseases ◽  
Retinal Light Damage ◽  
Age Related

Background: Oxidative stress is caused by free radicals or oxidant productions, including lipid peroxidation, protein modification, DNA damage and apoptosis or cell death and results in cellular degeneration and neurodegeneration from damage to macromolecules. Results: Accumulation of the DNA damage (8HOdG) products and the end products of LPO (including aldehyde, diene, triene conjugates and Schiff’s bases) were noted in the research studies. Significantly higher levels of these products in comparison with the controls were observed. Oxidative stress induced changes to ocular cells and tissues. Typical changes include ECM accumulation, cell dysfunction, cell death, advanced senescence, disarrangement or rearrangement of the cytoskeleton and released inflammatory cytokines. It is involved in ocular diseases, including keratoconus, Fuchs endothelial corneal dystrophy, and granular corneal dystrophy type 2, cataract, age-related macular degeneration, primary open-angle glaucoma, retinal light damage, and retinopathy of prematurity. These ocular diseases are the cause of irreversible blindness worldwide. Conclusions: Oxidative stress, inflammation and autophagy are implicated in biochemical and morphological changes in these ocular tissues. The development of therapy is a major target for the management care of these ocular diseases.

scholarly journals Tissue-specific regulation of the alpha-myosin heavy chain gene promoter in transgenic mice.

1991 ◽  
Vol 266 (36) ◽  
pp. 24613-24620
Author(s):  
A. Subramaniam ◽  
W.K. Jones ◽  
J. Gulick ◽  
S. Wert ◽  
J. Neumann ◽  
...  
Keyword(s):  
Transgenic Mice ◽  
Myosin Heavy Chain ◽  
Heavy Chain ◽  
Gene Promoter ◽  
Chain Gene ◽  
Heavy Chain Gene ◽  
Myosin Heavy Chain Gene ◽  
Tissue Specific ◽  
Specific Regulation

scholarly journals Evidence for existence of tissue-specific regulation of the mammalian pyruvate dehydrogenase complex

1998 ◽  
Vol 329 (1) ◽  
pp. 191-196 ◽  
Author(s):  
Melissa M. BOWKER-KINLEY ◽  
I. Wilhelmina DAVIS ◽  
Pengfei WU ◽  
A. Robert HARRIS ◽  
M. Kirill POPOV
Keyword(s):  
Tissue Distribution ◽  
Pyruvate Dehydrogenase ◽  
Pyruvate Dehydrogenase Complex ◽  
Pyruvate Dehydrogenase Kinase ◽  
Synthetic Analogue ◽  
Complex Activity ◽  
Acetyl Coa ◽  
Tissue Specific ◽  
Specific Regulation ◽  
Dehydrogenase Complex

Tissue distribution and kinetic parameters for the four isoenzymes of pyruvate dehydrogenase kinase (PDK1, PDK2, PDK3 and PDK4) identified thus far in mammals were analysed. It appeared that expression of these isoenzymes occurs in a tissue-specific manner. The mRNA for isoenzyme PDK1 was found almost exclusively in rat heart. The mRNA for PDK3 was most abundantly expressed in rat testis. The message for PDK2 was present in all tissues tested but the level was low in spleen and lung. The mRNA for PDK4 was predominantly expressed in skeletal muscle and heart. The specific activities of the isoenzymes varied 25-fold, from 50 nmol/min per mg for PDK2 to 1250 nmol/min per mg for PDK3. Apparent Ki values of the isoenzymes for the synthetic analogue of pyruvate, dichloroacetate, varied 40-fold, from 0.2 mM for PDK2 to 8 mM for PDK3. The isoenzymes were also different with respect to their ability to respond to NADH and NADH plus acetyl-CoA. NADH alone stimulated the activities of PDK1 and PDK2 by 20 and 30% respectively. NADH plus acetyl-CoA activated these isoenzymes nearly 200 and 300%. Under comparable conditions, isoenzyme PDK3 was almost completely unresponsive to NADH, and NADH plus acetyl-CoA caused inhibition rather than activation. Isoenzyme PDK4 was activated almost 2-fold by NADH, but NADH plus acetyl-CoA did not activate above the level seen with NADH alone. These results provide the first evidence that the unique tissue distribution and kinetic characteristics of the isoenzymes of PDK are among the major factors responsible for tissue-specific regulation of the pyruvate dehydrogenase complex activity.

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