scholarly journals Exploring the mitochondrial response to oxidative DNA damage in octocorals

2017 ◽  
Author(s):  
Gaurav G Shimpi ◽  
Sergio Vargas ◽  
Gert Wörheide
Keyword(s):  
Climate Change ◽  
Oxidative Stress ◽  
Copy Number ◽  
Low Ph ◽  
Host Cells ◽  
Climate Change Scenarios ◽  
Gene Repertoire ◽  
Mtdna Copy Number ◽  
Mtdna Damage ◽  
Ph Stress

Mitochondrial response to oxidative stress is intricately related to cellular homeostasis due to the high susceptibility of the mitochondrial genome to oxidative damage. Octocoral mitogenomes possess a unique DNA repair gene, mtMutS, potentially capable of counteracting the effects of oxidative stress induced mtDNA damage. Despite this unique feature, the response of octocoral mitochondria to increased oxidative stress remains unexplored. Here we explore the response of the octocoral Sinularia cf. cruciata to elevated temperature and low-pH stress and its ability to reverse acute oxidative mtDNA damage caused by exogenous agents like hydrogen peroxide (H2O2). The differential transcriptional response to these climate change-related stresses was recorded for two mtDNA-encoded genes and three stress biomarkers. Only HSP70 was significantly upregulated during thermal stress whereas significant reduction in the expression levels of HSP70, GPX, and COI was observed along with an increased number of mtMutS transcripts during low-pH stress. Damage to mtDNA was evident, accompanied by changes in mtDNA copy number. Damage caused by H2O2 toxicity was reversed within 5 hours and initial mtDNA copy number apparently influenced damage reversal. Our results indicate that different stress-specific resilience strategies are used by this octocoral species and its mitochondria to reverse oxidative stress and associated mtDNA damage. These experiments provide the first account on the response of octocoral mitochondria with its unique gene repertoire among animals to different stressors and highlight its potential role in conferring resilience to the host cells during different climate change scenarios.

scholarly journals Exploring the mitochondrial response to oxidative DNA damage in octocorals

2017 ◽  
Author(s):  
Gaurav G Shimpi ◽  
Sergio Vargas ◽  
Gert Wörheide
Keyword(s):  
Climate Change ◽  
Oxidative Stress ◽  
Copy Number ◽  
Low Ph ◽  
Host Cells ◽  
Climate Change Scenarios ◽  
Gene Repertoire ◽  
Mtdna Copy Number ◽  
Mtdna Damage ◽  
Ph Stress

Mitochondrial response to oxidative stress is intricately related to cellular homeostasis due to the high susceptibility of the mitochondrial genome to oxidative damage. Octocoral mitogenomes possess a unique DNA repair gene, mtMutS, potentially capable of counteracting the effects of oxidative stress induced mtDNA damage. Despite this unique feature, the response of octocoral mitochondria to increased oxidative stress remains unexplored. Here we explore the response of the octocoral Sinularia cf. cruciata to elevated temperature and low-pH stress and its ability to reverse acute oxidative mtDNA damage caused by exogenous agents like hydrogen peroxide (H2O2). The differential transcriptional response to these climate change-related stresses was recorded for two mtDNA-encoded genes and three stress biomarkers. Only HSP70 was significantly upregulated during thermal stress whereas significant reduction in the expression levels of HSP70, GPX, and COI was observed along with an increased number of mtMutS transcripts during low-pH stress. Damage to mtDNA was evident, accompanied by changes in mtDNA copy number. Damage caused by H2O2 toxicity was reversed within 5 hours and initial mtDNA copy number apparently influenced damage reversal. Our results indicate that different stress-specific resilience strategies are used by this octocoral species and its mitochondria to reverse oxidative stress and associated mtDNA damage. These experiments provide the first account on the response of octocoral mitochondria with its unique gene repertoire among animals to different stressors and highlight its potential role in conferring resilience to the host cells during different climate change scenarios.

scholarly journals Twinkle overexpression prevents cardiac rupture after myocardial infarction by alleviating impaired mitochondrial biogenesis

2016 ◽  
Vol 311 (3) ◽  
pp. H509-H519 ◽  
Author(s):  
Takahiro Inoue ◽  
Masataka Ikeda ◽  
Tomomi Ide ◽  
Takeo Fujino ◽  
Yuka Matsuo ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Myocardial Infarction ◽  
Mitochondrial Biogenesis ◽  
Copy Number ◽  
Cardiac Rupture ◽  
Mtdna Copy Number ◽  
Border Area ◽  
Frame Duplication ◽  
And Oxidative Stress

Cardiac rupture is a fatal complication after myocardial infarction (MI). However, the detailed mechanism underlying cardiac rupture after MI remains to be fully elucidated. In this study, we investigated the role of mitochondrial DNA (mtDNA) and mitochondria in the pathophysiology of cardiac rupture by analyzing Twinkle helicase overexpression mice (TW mice). Twinkle overexpression increased mtDNA copy number approximately twofold and ameliorated ischemic cardiomyopathy at day 28 after MI. Notably, Twinkle overexpression markedly prevented cardiac rupture and improved post-MI survival, accompanied by the suppression of MMP-2 and MMP-9 in the MI border area at day 5 after MI when cardiac rupture frequently occurs. Additionally, these cardioprotective effects of Twinkle overexpression were abolished in transgenic mice overexpressing mutant Twinkle with an in-frame duplication of amino acids 353–365, which resulted in no increases in mtDNA copy number. Furthermore, although apoptosis and oxidative stress were induced and mitochondria were damaged in the border area, these injuries were improved in TW mice. Further analysis revealed that mitochondrial biogenesis, including mtDNA copy number, transcription, and translation, was severely impaired in the border area at day 5. In contrast, Twinkle overexpression maintained mtDNA copy number and restored the impaired transcription and translation of mtDNA in the border area. These results demonstrated that Twinkle overexpression alleviated impaired mitochondrial biogenesis in the border area through maintained mtDNA copy number and thereby prevented cardiac rupture accompanied by the reduction of apoptosis and oxidative stress, and suppression of MMP activity.

scholarly journals Overexpression of TFAM or Twinkle Increases mtDNA Copy Number and Facilitates Cardioprotection Associated with Limited Mitochondrial Oxidative Stress

PLoS ONE ◽  
2015 ◽  
Vol 10 (3) ◽  
pp. e0119687 ◽  
Author(s):  
Masataka Ikeda ◽  
Tomomi Ide ◽  
Takeo Fujino ◽  
Shinobu Arai ◽  
Keita Saku ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Copy Number ◽  
Mtdna Copy Number ◽  
Mitochondrial Oxidative Stress

scholarly journals Climate change affects the parasitism rate and impairs the regulation of genes related to oxidative stress and ionoregulation of Colossoma macropomum

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Jaqueline Custodio da Costa ◽  
Samara Silva de Souza ◽  
Jonatas da Silva Castro ◽  
Renan Diego Amanajás ◽  
Adalberto Luis Val
Keyword(s):  
Climate Change ◽  
Oxidative Stress ◽  
Gene Expression ◽  
Climate Scenario ◽  
Climate Change Scenarios ◽  
Important Species ◽  
Colossoma Macropomum ◽  
Extreme Climate ◽  
Physiological Processes ◽  
Host Parasite

AbstractGlobal climate change represents a critical threat to the environment since it influences organismic interactions, such as the host-parasite systems, mainly in ectotherms including fishes. Rising temperature and CO2 are predicted to affect this interaction other and critical physiological processes in fish. Herein, we investigated the effects of different periods of exposure to climate change scenarios and to two degrees of parasitism by monogeneans in the host-parasite interaction, as well as the antioxidant and ionoregulatory responses of tambaqui (Colossoma macropomum), an important species in South American fishing and aquaculture. We hypothesized that temperature and CO2 changes in combination with parasite infection would interfere with the host’s physiological processes that are related to oxidative stress and ionoregulation. We experimentally exposed C. macropomum to low and high levels of parasitism in the current and extreme climate scenarios (4.5 °C and 900 ppm CO2 above current levels) for periods of seven and thirty days and we use as analyzed factors; the exposure time, the climate scenario and parasitism level in a 2 × 2 × 2 factorial through a three-way ANOVA as being fish the experimental unit (n = 8). An analysis of gill enzymatic and gene expression profile was performed to assess physiological (SOD, GPx and Na+/K+-ATPase enzymes) and molecular (Nrf2, SOD1, HIF-1α and NKA α1a genes) responses. A clear difference in the parasitism levels of individuals exposed to the extreme climate scenario was observed with a rapid and aggressive increase that was higher after 7 days of exposure though showed a decrease after 30 days. The combination of exposure to the extreme climate change scenario and parasitism caused oxidative stress and osmoregulatory disturbance, which was observed through the analysis of gene expression (Nrf2, SOD1, HIF-1α and NKA α1a) and antioxidant and ionoregulatory enzymes (SOD, GPx and Na+/K+-ATPase) on the host, possibly linked to inflammatory processes caused by the high degree of parasitism. In the coming years, these conditions may result in losses of performance for this species, and as such will represent ecological damage and economical losses, and result in a possible vulnerability in relation to food security.

scholarly journals Mitochondrial mutagenesis in BCR-ABL1-expressing cells sensitive and resistant to imatinib.

2016 ◽  
Vol 63 (2) ◽  
Author(s):  
Janusz Blasiak ◽  
Grazyna Hoser ◽  
Jolanta Bialkowska-Warzecha ◽  
Elzbieta Pawlowska ◽  
Tomasz Skorski
Keyword(s):  
Oxidative Stress ◽  
Cell Lines ◽  
Copy Number ◽  
Myeloid Leukemia ◽  
Genotoxic Stress ◽  
Inhibitory Effects ◽  
Apoptotic Pathway ◽  
Imatinib Resistance ◽  
Mtdna Damage ◽  
Cml Model

Imatinib revolutionized the treatment of chronic myeloid leukemia (CML) with the expression of the BCR-ABL1 tyrosine kinase, but imatinib resistance is an emerging problem. Imatinib can hinder the inhibitory effects of BCR-ABL1 on mitochondrial apoptotic pathway, so mitochondrial mutagenesis can be important for its action. To explore the mechanisms of imatinib resistance we created a mouse-derived CML model cells consisting of parental 32D cells (P) and cells transfected with the BCR-ABL1 gene (S cells) or its variants with the Y253H or T315I mutations (253 and 315 cells, respectively), conferring resistance to imatinib. A fraction of the S cells was cultured in increasing concentrations of imatinib, acquiring resistance to this drug (AR cells). The 253, 315 and AR cells, in contrast to S cells, displayed resistance to imatinib. We observed that the T315I cells displayed greater extent of H2O2-induced mtDNA damage than their imatinib-sensitive counterparts. No difference in the sensitivity to UV radiation was observed among all the cell lines. A decrease in the extent of H2O2-induced mtDNA damage was observed during a 120-min repair incubation in all cell lines, but it was significant only in imatinib-sensitive and T315I cells. No difference in the copy number of mtDNA and frequency of the 3,867-bp deletion was observed and genotoxic stress induced by H2O2 or UV did not change this relationship. In conclusion, some aspects of mtDNA mutagenesis, including sensitivity to oxidative stress and DNA repair can contribute to imatinib resistance in BCR-ABL1-expressing cells.

scholarly journals Increase of mitochondria and mitochondrial DNA in response to oxidative stress in human cells

2000 ◽  
Vol 348 (2) ◽  
pp. 425-432 ◽  
Author(s):  
Hsin-Chen LEE ◽  
Pen-Hui YIN ◽  
Ching-You LU ◽  
Chin-Wen CHI ◽  
Yau-Huei WEI
Keyword(s):  
Oxidative Stress ◽  
Cell Cycle ◽  
Mitochondrial Dna ◽  
Copy Number ◽  
Human Cells ◽  
Dependent Manner ◽  
Mtdna Copy Number ◽  
Human Lung Fibroblast ◽  
Mitochondrial Mass ◽  
Enhanced Production

Mitochondrial respiratory function is impaired in the target tissues of patients with mitochondrial diseases and declines with age in various human tissues. It is generally accepted that respiratory-chain defects result in enhanced production of reactive oxygen species and free radicals in mitochondria. Recently, we have demonstrated that the copy number of mitochondrial DNA (mtDNA) is increased in the lung tissues of elderly human subjects. The mtDNA copy number was suggested to be increased by a feedback mechanism that compensates for defects in mitochondria harbouring mutated mtDNA and a defective respiratory system. However, the detailed mechanism remains unclear. In this study, we treated a human lung fibroblast cell line, MRC-5, with H2O2 at concentrations of 90-360 μM. After the treatment for 24-72 h, we found that cells were arrested at G0 and G1 phases but that mitochondrial mass and mtDNA content were significantly increased in a concentration- and time-dependent manner. Moreover, the oxidative stress induced by buthionine sulphoximine was also found to cause an increase in mitochondrial mass of the treated cells. Increased uptake of a vital mitochondrial dye Rhodamine 123 and enhanced tetrazolium [MTT, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide] reduction revealed that the mitochondria increased by H2O2 treatment were functional. In addition, the increase in the mitochondrial mass was also observed in cell-cycle-arrested cells induced by mimosine, lovastatin and genistein. Taken together, these findings suggest that the increase in mitochondrial mass and mtDNA content are the early molecular events of human cells in response to endogenous or exogenous oxidative stress through cell-cycle arrest.

scholarly journals Dihydromyricetin Improves Endothelial Dysfunction in Diabetic Mice via Oxidative Stress Inhibition in a SIRT3-Dependent Manner

2020 ◽  
Vol 21 (18) ◽  
pp. 6699
Author(s):  
Yu-Yun Hua ◽  
Yue Zhang ◽  
Wei-Wei Gong ◽  
Yue Ding ◽  
Jie-Ru Shen ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Endothelial Dysfunction ◽  
Thoracic Aorta ◽  
Copy Number ◽  
Hba1c Level ◽  
Dependent Manner ◽  
Ros Production ◽  
Diabetic Mice ◽  
Mtdna Copy Number ◽  
Endothelium Dependent Relaxation

Dihydromyricetin (DHY), a flavonoid component isolated from Ampelopsis grossedentata, exerts versatile pharmacological activities. However, the possible effects of DHY on diabetic vascular endothelial dysfunction have not yet been fully elucidated. In the present study, male C57BL/6 mice, wild type (WT) 129S1/SvImJ mice and sirtuin 3 (SIRT3) knockout (SIRT3-/-) mice were injected with streptozotocin (STZ, 60 mg/kg/day) for 5 consecutive days. Two weeks later, DHY were given at the doses of 250 mg/kg by gavage once daily for 12 weeks. Fasting blood glucose (FBG) and glycosylated hemoglobin (HbA1c) level, endothelium-dependent relaxation of thoracic aorta, reactive oxygen species (ROS) production, SIRT3, and superoxide dismutase 2 (SOD2) protein expressions, as well as mitochondrial Deoxyribonucleic Acid (mtDNA) copy number, in thoracic aorta were detected. Our study found that DHY treatment decreased FBG and HbA1c level, improved endothelium-dependent relaxation of thoracic aorta, inhibited oxidative stress and ROS production, and enhanced SIRT3 and SOD2 protein expression, as well as mtDNA copy number, in thoracic aorta of diabetic mice. However, above protective effects of DHY were unavailable in SIRT3-/- mice. The study suggested DHY improved endothelial dysfunction in diabetic mice via oxidative stress inhibition in a SIRT3-dependent manner.

scholarly journals The effects of some imidazopyrazine derivatives on telomerase inhibition, mtdna damage and mtdna copy number

2017 ◽  
Vol 55 (3) ◽  
pp. 31
Author(s):  
Ayşe Gül Mutlu ◽  
Abdulkerim Bilginer ◽  
Ismail Kayağil ◽  
Hülya Yıldız ◽  
Ülkü Bayhan ◽  
...  
Keyword(s):  
Copy Number ◽  
Mtdna Copy Number ◽  
Telomerase Inhibition ◽  
Mtdna Damage

Abstract 476: Mitochondrial DNA Preservation Preserves Cardiac Function Following Sudden Cardiac Arrest

2020 ◽  
Vol 127 (Suppl_1) ◽  
Author(s):  
Cody A Rutledge ◽  
Kevin Redding ◽  
Cameron Dezfulian ◽  
Brett A Kaufman
Keyword(s):  
Mitochondrial Dna ◽  
Cardiac Arrest ◽  
Cardiac Function ◽  
Copy Number ◽  
Sudden Cardiac Arrest ◽  
Spontaneous Circulation ◽  
Mitochondrial Morphology ◽  
Mtdna Copy Number ◽  
Mtdna Damage ◽  
And Function

Background: Sudden cardiac arrest (SCA) affects over 350,000 Americans yearly with greater than 70% mortality. Survivors frequently develop cardiomyopathy after SCA. Cardiac reperfusion causes mitochondrial ROS production, which is known to damage mitochondrial DNA (mtDNA), but the physiologic consequences of mtDNA damage are unclear. We investigated the role of mtDNA damage by altering the expression of TFAM, a nuclear-encoded transcription factor that protects mtDNA from ROS, in a mouse model of SCA. Methods: WT and transgenic mice featuring cardiac-specific TFAM overexpression (TFAM-OE) and under-expression (TFAM Flox) underwent either 8 min of SCA or sham surgery followed by cardiopulmonary resuscitation. Survivors were assessed by echocardiography at 1-day, 1-week, and 4-weeks. Tissues were collected for assessment of mtDNA copy number and damage and assessment of mitochondrial morphology, protein expression, and function. Results: WT, TFAM-OE, and TFAM Flox mice had no significant changes to baseline body weight or ejection fraction (EF). There were no changes in time to return of spontaneous circulation or body temperature between groups. 1 day after SCA, WT mice have reduced EF (38.49±3.76%) compared to sham WT mice (59.73±1.42). EF is protected in TFAM-OE mice (51.11±2.95%) and exacerbated in TFAM-UE mice (29.36±5.40%). TFAM-OE have significantly higher survival at 4 weeks (80%, 8 of 10) when compared to WT mice (38%, 5 of 13), but there is no change in TFAM-Flox mice (43%, 3 of 7). TFAM OE mice have higher mtDNA copy number and lower mtDNA damage when compared to WT mice. Conclusions: TFAM OE protects cardiac function 1-day after SCA and improves 4-week survival. This is likely driven by TFAM-mediated protection of mtDNA. TFAM-Flox mice have lower EF at one day but no change to survival. This work suggests a role for mtDNA damage as a mechanism and potential therapeutic target of cardiomyopathy after SCA.

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