scholarly journals The RNase Rny1p cleaves tRNAs and promotes cell death during oxidative stress in Saccharomyces cerevisiae

2009 ◽  
Vol 185 (1) ◽  
pp. 43-50 ◽  
Author(s):  
Debrah M. Thompson ◽  
Roy Parker
Keyword(s):  
Oxidative Stress ◽  
Cell Death ◽  
Cell Survival ◽  
Cellular Response ◽  
Cellular Damage ◽  
Transfer Rnas ◽  
Endonucleolytic Cleavage ◽  
Response To Stress ◽  
Rnase T2

The cellular response to stress conditions involves a decision between survival or cell death when damage is severe. A conserved stress response in eukaryotes involves endonucleolytic cleavage of transfer RNAs (tRNAs). The mechanism and significance of such tRNA cleavage is unknown. We show that in yeast, tRNAs are cleaved by the RNase T2 family member Rny1p, which is released from the vacuole into the cytosol during oxidative stress. Rny1p modulates yeast cell survival during oxidative stress independently of its catalytic ability. This suggests that upon release to the cytosol, Rny1p promotes cell death by direct interactions with downstream components. Thus, detection of Rny1p, and possibly its orthologues, in the cytosol may be a conserved mechanism for assessing cellular damage and determining cell survival, analogous to the role of cytochrome c as a marker for mitochondrial damage.

The Cellular Control Enzyme PolyADP Ribosyl Transferase Is Eliminated in Cultured Fanconi Anemia Fibroblasts at Confluency

2003 ◽  
Vol 384 (1) ◽  
pp. 169-174 ◽  
Author(s):  
M.H. Ramirez ◽  
C. Adelfalk ◽  
M. Kontou ◽  
M. Hirsch-Kauffmann ◽  
M. Schweiger
Keyword(s):  
Oxidative Stress ◽  
Cell Death ◽  
Redox Potential ◽  
Cell Survival ◽  
Fanconi Anemia ◽  
Hereditary Disease ◽  
Pathogenic Mechanisms ◽  
Complementation Groups ◽  
Cellular Control

AbstractFanconi anemia (FA) is a hereditary disease of unknown pathogenic mechanisms, although mutations in seven different genes can be causative. Six of these genes have been cloned and sequenced. Only slight homology to the DNA of any other known gene has been found with the exception of FANCG which is identical to XRCC9. The function of these genes, including XRCC9, is presently unknown. Since pADP ribosyl transferase (pADPRT) plays a role in apoptosis, and apoptosis is affected in FA cells, we studied the correlation between pADPRT and FA cells. We reinvestigated the previously reported lack of pADPRT activity in fibroblasts from patients with Fanconi anemia. Here we describe the role of the lower redox potential of FA cells and demonstrate that this is an efficient strategy in the prevention of cell death due to the lack of energy under oxidative stress. This strategy is advantageous for the cells under the nonreplicative condition of confluency in which the risk of mutation is low and the prevention of apoptosis permits cell survival. pADPRT is not diminished to the same extent in all complementation groups of FA. It is prominent in FANCA, FANCG and FANCF cells, indicating that these genes control pADPRT diminution. Our experiments suggest that the pADPRT level is linked with the oxidoreduction reactions seen in FA.

scholarly journals Multiple ribonuclease A family members cleave transfer RNAs in response to stress

2019 ◽  
Author(s):  
Yasutoshi Akiyama ◽  
Shawn Lyons ◽  
Marta M. Fay ◽  
Takaaki Abe ◽  
Paul Anderson ◽  
...  
Keyword(s):  
Cell Survival ◽  
Family Members ◽  
Rnase A ◽  
Transfer Rnas ◽  
Cellular Processes ◽  
Stress Changes ◽  
Response To Stress ◽  
Rnase A Superfamily

ABSTRACTDuring stress, changes in gene expression are critical for cell survival. Stress-induced tRNA cleavage has been implicated in various cellular processes, where tRNA fragments play diverse regulatory roles. Angiogenin (ANG), a member of the RNase A superfamily, induces cleavage of tRNAs resulting in the formation of tRNA-derived stress-induced RNAs (tiRNAs) that contribute to translational reprogramming aiming at cell survival. The role of other stress-induced RNases in tRNA cleavage is poorly understood. Using gene editing and biochemical approaches, we show that other members of the RNase A family are capable of targeting tRNAs in stress-responsive manner. We show that in the absence of ANG, these RNases also promote the production of tiRNAs. Moreover, specific stresses (such as treatment with sodium arsenite) activate cleavage of universal 3’-CCA termini of tRNAs in ANG-independent fashion in living cells. We conclude that multiple RNase A family members are capable of targeting tRNAs in a stress-specific manner in vivo.

scholarly journals The function of autophagy as a fundamental process of preserving cell homeostasis

2021 ◽  
Vol 12 (1) ◽  
pp. 81-89
Author(s):  
Nikolina Elez-Burnjaković ◽  
Lejla Pojskić ◽  
Sanin Haverić ◽  
Ajla Smajlović
Keyword(s):  
Cell Death ◽  
Cell Survival ◽  
Metabolic Stress ◽  
Type I ◽  
Nutrient Deficiencies ◽  
Cancer Cell Death ◽  
Cell Death Pathway ◽  
Response To Stress ◽  
Cytoplasmic Content

Autophagy is a dynamic process, conserved in all eukaryotes. It is responsible for the degradation of cytoplasmic content. Autophagy is crucial in cell survival and cell death. It plays a significant role in the cell response to stress, nutrient deficiencies, embryonic development, tumor suppression, response to pathogens and aging. The process of autophagy is also involved in the pathology of human diseases, such as cancer, diabetes, cardiomyopathy, and neurodegenerative diseases such as Alzheimer's and Parkinson's disease. Autophagy is a mechanism that involves degradation of cells, proteins, damaged organelles and pathogens through the lysosomal mechanisms, thus autophagy supports cell survival during starvation, hypoxia and metabolic stress. However, if extensive and/or excessive, autophagy can promote apoptosis (type I) or function as an alternative cell-death pathway, called autophagic cell death (type II). Autophagy can either promote cancer cell death, or serve as a survival mechanism against apoptosis or necrosis induced by various anticancer treatments. Given the contradictory role of autophagy during tumor initiation and progression, the use of autophagy in therapy depends on the context and must be approached individually

scholarly journals Role of hepcidin in oxidative stress and cell death of cultured mouse renal collecting duct cells: protection against iron and sensitization to cadmium

2021 ◽  
Author(s):  
Stephanie Probst ◽  
Johannes Fels ◽  
Bettina Scharner ◽  
Natascha A. Wolff ◽  
Eleni Roussa ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Cell Death ◽  
Cell Fate ◽  
Catalase Activity ◽  
Metal Ion ◽  
Iron Homeostasis ◽  
Collecting Duct ◽  
Duct Cell ◽  
Plasmid Transfection

AbstractThe liver hormone hepcidin regulates systemic iron homeostasis. Hepcidin is also expressed by the kidney, but exclusively in distal nephron segments. Several studies suggest hepcidin protects against kidney damage involving Fe2+ overload. The nephrotoxic non-essential metal ion Cd2+ can displace Fe2+ from cellular biomolecules, causing oxidative stress and cell death. The role of hepcidin in Fe2+ and Cd2+ toxicity was assessed in mouse renal cortical [mCCD(cl.1)] and inner medullary [mIMCD3] collecting duct cell lines. Cells were exposed to equipotent Cd2+ (0.5–5 μmol/l) and/or Fe2+ (50–100 μmol/l) for 4–24 h. Hepcidin (Hamp1) was transiently silenced by RNAi or overexpressed by plasmid transfection. Hepcidin or catalase expression were evaluated by RT-PCR, qPCR, immunoblotting or immunofluorescence microscopy, and cell fate by MTT, apoptosis and necrosis assays. Reactive oxygen species (ROS) were detected using CellROX™ Green and catalase activity by fluorometry. Hepcidin upregulation protected against Fe2+-induced mIMCD3 cell death by increasing catalase activity and reducing ROS, but exacerbated Cd2+-induced catalase dysfunction, increasing ROS and cell death. Opposite effects were observed with Hamp1 siRNA. Similar to Hamp1 silencing, increased intracellular Fe2+ prevented Cd2+ damage, ROS formation and catalase disruption whereas chelation of intracellular Fe2+ with desferrioxamine augmented Cd2+ damage, corresponding to hepcidin upregulation. Comparable effects were observed in mCCD(cl.1) cells, indicating equivalent functions of renal hepcidin in different collecting duct segments. In conclusion, hepcidin likely binds Fe2+, but not Cd2+. Because Fe2+ and Cd2+ compete for functional binding sites in proteins, hepcidin affects their free metal ion pools and differentially impacts downstream processes and cell fate.

Combination of photodynamic therapy with doxorubicin in osteosarcoma: Cell death and the role of oxidative stress

2016 ◽  
Vol 61 ◽  
pp. S141
Author(s):  
B. Serambeque ◽  
G. Brites ◽  
M. Laranjo ◽  
G. Chohfi de Miguel ◽  
A. Serra ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Cell Death ◽  
Photodynamic Therapy ◽  
Osteosarcoma Cell

Re-Examination of the Exacerbating Effect of Inflammasome Components during Radiation Injury

2021 ◽  
Author(s):  
W. June Brickey ◽  
Michael A. Thompson ◽  
Zhecheng Sheng ◽  
Zhiguo Li ◽  
Kouros Owzar ◽  
...  
Keyword(s):  
Cellular Response ◽  
Radiation Injury ◽  
Therapeutic Benefit ◽  
Acute Radiation ◽  
Cellular Damage ◽  
Inflammatory Factors ◽  
Experimental Conditions ◽  
Acute Radiation Injury ◽  
Radiation Induced

Radiation can be applied for therapeutic benefit against cancer or may result in devastating harm due to accidental or intentional release of nuclear energy. In all cases, radiation exposure causes molecular and cellular damage, resulting in the production of inflammatory factors and danger signals. Several classes of innate immune receptors sense the released damage associated molecules and activate cellular response pathways, including the induction of inflammasome signaling that impacts IL-1β/IL-18 maturation and cell death. A previous report indicated inflammasomes aggravate acute radiation syndrome. In contrast, here we find that inflammasome components do not exacerbate gamma-radiation-induced injury by examining heterozygous and gene-deletion littermate controls in addition to wild-type mice. Absence of some inflammasome genes, such as caspase-1/11 and Nlrp3, enhance susceptibility of treated mice to acute radiation injury, indicating importance of the inflammasome pathway in radioprotection. Surprisingly, we discover that the survival outcome may be sex-dependent as more inflammasome-deficient male mice are susceptible to radiation-induced injury. We discuss parameters that may influence the role of inflammasomes as radioprotective or radioexacerbating factors in recovery from radiation injury including the use of littermate controls, the sex of the animals, differences in microbiota within the colonies and other experimental conditions. Under the conditions tested, inflammasome components do not exacerbate radiation injury, but rather provide protective benefit.

scholarly journals Effects of Caloric Restriction on Cardiac Oxidative Stress and Mitochondrial Bioenergetics: Potential Role of Cardiac Sirtuins

2013 ◽  
Vol 2013 ◽  
pp. 1-11 ◽  
Author(s):  
Ken Shinmura
Keyword(s):  
Oxidative Stress ◽  
Free Radical ◽  
Oxidative Damage ◽  
Caloric Restriction ◽  
Functional Decline ◽  
Cellular Damage ◽  
Free Radical Theory ◽  
Radical Theory ◽  
Stress Theory

The biology of aging has not been fully clarified, but the free radical theory of aging is one of the strongest aging theories proposed to date. The free radical theory has been expanded to the oxidative stress theory, in which mitochondria play a central role in the development of the aging process because of their critical roles in bioenergetics, oxidant production, and regulation of cell death. A decline in cardiac mitochondrial function associated with the accumulation of oxidative damage might be responsible, at least in part, for the decline in cardiac performance with age. In contrast, lifelong caloric restriction can attenuate functional decline with age, delay the onset of morbidity, and extend lifespan in various species. The effect of caloric restriction appears to be related to a reduction in cellular damage induced by reactive oxygen species. There is increasing evidence that sirtuins play an essential role in the reduction of mitochondrial oxidative stress during caloric restriction. We speculate that cardiac sirtuins attenuate the accumulation of oxidative damage associated with age by modifying specific mitochondrial proteins posttranscriptionally. Therefore, the distinct role of each sirtuin in the heart subjected to caloric restriction should be clarified to translate sirtuin biology into clinical practice.

scholarly journals Assessment of the Impact of Post-Thaw Stress Pathway Modulation on Cell Recovery following Cryopreservation in a Hematopoietic Progenitor Cell Model

Cells ◽  
2022 ◽  
Vol 11 (2) ◽  
pp. 278
Author(s):  
John M. Baust ◽  
Kristi K. Snyder ◽  
Robert G. Van Buskirk ◽  
John G. Baust
Keyword(s):  
Oxidative Stress ◽  
Cell Death ◽  
Cell Survival ◽  
Critical Role ◽  
Hematopoietic Progenitor Cell ◽  
Scale Production ◽  
Cell Recovery ◽  
Hematopoietic Progenitor ◽  
Discovery Science ◽  
The Impact

The development and use of complex cell-based products in clinical and discovery science continues to grow at an unprecedented pace. To this end, cryopreservation plays a critical role, serving as an enabling process, providing on-demand access to biological material, facilitating large scale production, storage, and distribution of living materials. Despite serving a critical role and substantial improvements over the last several decades, cryopreservation often remains a bottleneck impacting numerous areas including cell therapy, tissue engineering, and tissue banking. Studies have illustrated the impact and benefit of controlling cryopreservation-induced delayed-onset cell death (CIDOCD) through various “front end” strategies, such as specialized media, new cryoprotective agents, and molecular control during cryopreservation. While proving highly successful, a substantial level of cell death and loss of cell function remains associated with cryopreservation. Recently, we focused on developing technologies (RevitalICE™) designed to reduce the impact of CIDOCD through buffering the cell stress response during the post-thaw recovery phase in an effort to improve the recovery of previously cryopreserved samples. In this study, we investigated the impact of modulating apoptotic caspase activation, oxidative stress, unfolded protein response, and free radical damage in the initial 24 h post-thaw on overall cell survival. Human hematopoietic progenitor cells in vitro cryopreserved in both traditional extracellular-type and intracellular-type cryopreservation freeze media were utilized as a model cell system to assess impact on survival. Our findings demonstrated that through the modulation of several of these pathways, improvements in cell recovery were obtained, regardless of the freeze media and dimethyl sulfoxide concentration utilized. Specifically, through the use of oxidative stress inhibitors, an average increase of 20% in overall viability was observed. Furthermore, the results demonstrated that by using the post-thaw recovery reagent on samples cryopreserved in intracellular-type media (Unisol™), improvements in overall cell survival approaching 80% of non-frozen controls were attained. While improvements in overall survival were obtained, an assessment on the impact of specific cell subpopulations and functionality remains to be completed. While work remains, these results represent an important step forward in the development of improved cryopreservation processes for use in discovery science, and commercial and clinical settings.

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