Biphasic Induction of HO-1 in Macrophages Treated with Lipopolysaccharide: Role of HO-1 Induction in Cell Survival from Oxidative Stress

In the present work, the role of the carboxyl group of o-dihydroxybenzoic acids (pyrocatechuic, 2,3-diOH-BA and protocatechuic, 3,4-diOH-BA) on the protection against induced oxidative stress in Saccharomyces cerevisiae was examined. Catechol (3,4-diOH-B) was included for comparison. Cell survival, antioxidant enzyme activities, and TBARS level were used to evaluate the efficiency upon the stress induced by H2O2 or cumene hydroperoxide. Theoretical calculation of atomic charge values, dipole moment, and a set of indices relevant to the redox properties of the compounds was also carried out in the liquid phase (water). Irrespective of the oxidant used, 2,3-diOH-BA required by far the lowest concentration (3–5 μM) to facilitate cell survival. The two acids did not activate catalase but reduced superoxide dismutase activity (3,4-diOH-BA>2,3-diOH-BA). TBARS assay showed an antioxidant effect only when H2O2 was used; equal activity for the two acids and inferior to that of 3,4-diOH B. Overall, theoretical and experimental findings suggest that the 2,3-diOH-BA high activity should be governed by metal chelation. In the case of 3,4-diOH BA, radical scavenging increases, and chelation capacity decreases. The lack of carboxyl moiety (3,4-diOH B) adds to radical scavenging, interaction with lipophilic free radicals, and antioxidant enzymes. The present study adds to our knowledge of the antioxidant mechanism of dietary phenols in biological systems.

Download Full-text

Celastrol and Melatonin Modify SIRT1, SIRT6 and SIRT7 Gene Expression and Improve the Response of Human Granulosa-Lutein Cells to Oxidative Stress

Antioxidants ◽

10.3390/antiox10121871 ◽

2021 ◽

Vol 10 (12) ◽

pp. 1871

Author(s):

Rita Martín-Ramírez ◽

Rebeca González-Fernández ◽

Jairo Hernández ◽

Pablo Martín-Vasallo ◽

Angela Palumbo ◽

...

Keyword(s):

Oxidative Stress ◽

Gene Expression ◽

Free Radical ◽

Cell Survival ◽

Direct Effect ◽

Free Radical Scavenger ◽

Radical Scavenger ◽

Protective Agent ◽

Physiological Processes

An excess of oxidative stress (OS) may affect several physiological processes fundamental to reproduction. SIRT1, SIRT6 and SIRT7 are involved in protection stress systems caused by OS, and they can be activated by antioxidants such as celastrol or melatonin. In this study, we evaluate SIRT1, SIRT6 and SIRT7 gene expression in cultured human granulosa-lutein (hGL) cells in response to OS inductors (glucose or peroxynitrite) and/or antioxidants. Our results show that celastrol and melatonin improve cell survival in the presence and absence of OS inductors. In addition, melatonin induced SIRT1, SIRT6 and SIRT7 gene expression while celastrol only induced SIRT7 gene expression. This response was not altered by the addition of OS inductors. Our previous data for cultured hGL cells showed a dual role of celastrol as a free radical scavenger and as a protective agent by regulating gene expression. This study shows a direct effect of celastrol on SIRT7 gene expression. Melatonin may protect from OS in a receptor-mediated manner rather than as a scavenger. In conclusion, our results show increased hGL cells survival with melatonin or celastrol treatment under OS conditions, probably through the regulation of nuclear sirtuins’ gene expression.

Download Full-text

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

The Journal of Cell Biology ◽

10.1083/jcb.200811119 ◽

2009 ◽

Vol 185 (1) ◽

pp. 43-50 ◽

Cited By ~ 183

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.

Download Full-text

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

Biological Chemistry ◽

10.1515/bc.2003.018 ◽

2003 ◽

Vol 384 (1) ◽

pp. 169-174 ◽

Cited By ~ 3

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.

Download Full-text

Escherichia coli genes involved in cell survival during dormancy: Role of oxidative stress

Biochemical and Biophysical Research Communications ◽

10.1016/0006-291x(92)91338-q ◽

1992 ◽

Vol 188 (3) ◽

pp. 1054-1059 ◽

Cited By ~ 30

Author(s):

Abraham Eisenstark ◽

Cathy Miller ◽

Joyce Jones ◽

Sara Leven

Keyword(s):

Oxidative Stress ◽

Escherichia Coli ◽

Cell Survival

Download Full-text

Integrated Stress Response Couples Mitochondrial Protein Translation with Oxidative Stress Control

Circulation ◽

10.1161/circulationaha.120.053125 ◽

2021 ◽

Author(s):

Guangyu Zhang ◽

Xiaoding Wang ◽

Chao Li ◽

Qinfeng Li ◽

Yu A. An ◽

...

Keyword(s):

Oxidative Stress ◽

Myocardial Infarction ◽

Coronary Artery ◽

Stress Response ◽

Cell Survival ◽

Mitochondrial Protein ◽

Cardiac Cell ◽

Mitochondrial Complex

Background: The integrated stress response (ISR) is an evolutionarily conserved process to cope with intracellular and extracellular disturbances. Myocardial infarction is a leading cause of death worldwide. Coronary artery reperfusion is the most effective means to mitigate cardiac damage of myocardial infarction, which however causes additional reperfusion injury. This study aimed to investigate the role of the ISR in myocardial ischemia/reperfusion (I/R). Methods: Cardiac-specific gain- and loss-of-function approaches for the ISR were employed in vivo . Myocardial I/R was achieved by the ligation of the cardiac left anterior descending artery for 45 minutes, followed by reperfusion for different times. Cardiac function was assessed by echocardiography. Additionally, cultured H9c2 cells, primary rat cardiomyocytes, and mouse embryonic fibroblasts were used to dissect underlying molecular mechanisms. Moreover, tandem mass tag (TMT) labeling and mass spectrometry was conducted to identify protein targets of the ISR. Pharmacological means were tested to manipulate the ISR for therapeutic exploration. Results: We show that the PERK/eIF2α axis of the ISR is strongly induced by I/R in cardiomyocytes in vitro and in vivo . We further reveal a physiological role of PERK/eIF2α signaling by showing that acute activation of PERK in the heart confers robust cardioprotection against reperfusion injury. In contrast, cardiac-specific deletion of PERK aggravates cardiac responses to reperfusion. Mechanistically, the ISR directly targets mitochondrial complexes via translational suppression. We identify NDUFAF2, an assembly factor of mitochondrial complex I, as a selective target of PERK. Overexpression of PERK suppresses the protein expression of NDUFAF2 while PERK inhibition causes an increase of NDUFAF2. Silencing of NDUFAF2 significantly rescues cardiac cell survival from PERK knockdown under I/R. Further, we show that activation of PERK/eIF2α signaling reduces mitochondrial complex-derived reactive oxygen species and improves cardiac cell survival in response to I/R. Moreover, pharmacological stimulation of the ISR protects the heart against reperfusion damage, even after the restoration of occluded coronary artery, highlighting a clinical relevance for myocardial infarction treatment. Conclusions: These studies suggest that the ISR improves cell survival and mitigate reperfusion damage by selectively suppressing mitochondrial protein synthesis and reducing oxidative stress in the heart.

Download Full-text

Role of Beclin-1-Mediated Autophagy in the Survival of Pediatric Leukemia Cells

Cellular Physiology and Biochemistry ◽

10.1159/000447882 ◽

2016 ◽

Vol 39 (5) ◽

pp. 1827-1836 ◽

Cited By ~ 12

Author(s):

Xiaoli Wu ◽

Xuefeng Feng ◽

Xiaoqing Zhao ◽

Futian Ma ◽

Na Liu ◽

...

Keyword(s):

Oxidative Stress ◽

Cell Survival ◽

Marrow Cell ◽

Beclin 1 ◽

Luciferase Reporter ◽

Pediatric Leukemia ◽

Protein Levels ◽

High Level

Background/Aims: Acute and chronic leukemia are severe malignant cancers worldwide, and can occur in pediatric patients. Since bone marrow cell transplantation is seriously limited by the availability of the immune-paired donor sources, the therapy for pediatric leukemia (PL) remains challenging. Autophagy is essential for the regulation of cell survival in the harsh environment. However, the role of autophagy in the survival of PL cells under the oxidative stress, e.g. chemotherapy, remain ill-defined. In the current study, we addressed these questions. Methods: We analyzed the effects of oxidative stress on the cell viability of PL cells in vitro, using a CCK-8 assay. We analyzed the effects of oxidative stress on the apoptosis and autophagy of PL cells. We analyzed the levels of Beclin-1 and microRNA-93 (miR-93) in PL cells. Prediction of binding between miR-93 and 3'-UTR of Beclin-1 mRNA was performed by a bioinformatics algorithm and confirmed by a dual luciferase reporter assay. The relationship between levels of miR-93 and patients' survival was analyzed in PL patients. Results: We found that oxidative stress dose-dependently increased autophagy in PL cells. While low-level oxidative stress did not increase apoptosis, high-level oxidative stress increased apoptosis, seemingly from failure of autophagy-mediated cell survival. High-level oxidative stress appeared to suppress the protein levels of an autophagy protein Beclin-1 in PL cells, possibly through induction of miR-93, which inhibited the translation of Beclin-1 mRNA via 3'-UTR binding. Conclusion: Beclin-1-mediated autophagy plays a key role in the survival of PL cells against oxidative stress. Induction of miR-93 may increase the sensitivity of PL cells to oxidative stress during chemotherapy to improve therapeutic outcome.

Download Full-text