scholarly journals SIRT3 Is a Stress-Responsive Deacetylase in Cardiomyocytes That Protects Cells from Stress-Mediated Cell Death by Deacetylation of Ku70

2008 ◽  
Vol 28 (20) ◽  
pp. 6384-6401 ◽  
Author(s):  
Nagalingam R. Sundaresan ◽  
Sadhana A. Samant ◽  
Vinodkumar B. Pillai ◽  
Senthilkumar B. Rajamohan ◽  
Mahesh P. Gupta
Keyword(s):  
Oxidative Stress ◽  
Cell Death ◽  
Gene Regulation ◽  
Essential Role ◽  
Short Form ◽  
Biological Functions ◽  
Proapoptotic Protein ◽  
Long Form ◽  
And Oxidative Stress

ABSTRACT There are seven SIRT isoforms in mammals, with diverse biological functions including gene regulation, metabolism, and apoptosis. Among them, SIRT3 is the only sirtuin whose increased expression has been shown to correlate with an extended life span in humans. In this study, we examined the role of SIRT3 in murine cardiomyocytes. We found that SIRT3 is a stress-responsive deacetylase and that its increased expression protects myocytes from genotoxic and oxidative stress-mediated cell death. We show that, like human SIRT3, mouse SIRT3 is expressed in two forms, a ∼44-kDa long form and a ∼28-kDa short form. Whereas the long form is localized in the mitochondria, nucleus, and cytoplasm, the short form is localized exclusively in the mitochondria of cardiomyocytes. During stress, SIRT3 levels are increased not only in mitochondria but also in the nuclei of cardiomyocytes. We also identified Ku70 as a new target of SIRT3. SIRT3 physically binds to Ku70 and deacetylates it, and this promotes interaction of Ku70 with the proapoptotic protein Bax. Thus, under stress conditions, increased expression of SIRT3 protects cardiomyocytes, in part by hindering the translocation of Bax to mitochondria. These studies underscore an essential role of SIRT3 in the survival of cardiomyocytes in stress situations.

Abstract 3731: TSC deficiency unmasks a novel protective role of RIP1/RIP3 signaling against mitochondrial and oxidative stress-induced cell death

2016 ◽  
Author(s):  
Piotr T. Filipczak ◽  
Cindy Thomas ◽  
Wenshu Chen ◽  
Andrew Salzman ◽  
Jacob D. McDonald ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Cell Death ◽  
Protective Role ◽  
And Oxidative Stress

scholarly journals Role of STAT1 and Oxidative Stress in Gentamicin-Induced Hair Cell Death in Organ of Corti

2016 ◽  
Vol 37 (9) ◽  
pp. 1449-1456 ◽  
Author(s):  
Peng Jiang ◽  
Amrita Ray ◽  
Leonard P. Rybak ◽  
Michael J. Brenner
Keyword(s):  
Oxidative Stress ◽  
Cell Death ◽  
Hair Cell ◽  
Organ Of Corti ◽  
Hair Cell Death ◽  
And Oxidative Stress

scholarly journals Human INCL fibroblasts display abnormal mitochondrial and lysosomal networks and heightened susceptibility to ROS-induced cell death

2020 ◽  
Author(s):  
Bailey Balouch ◽  
Halle Nagorsky ◽  
Truc Pham ◽  
Thai LaGraff ◽  
Quynh Chu-LaGraff
Keyword(s):  
Oxidative Stress ◽  
Cell Death ◽  
Molecular Mechanisms ◽  
Neurodegenerative Disorder ◽  
Endoplasmic Reticulum Stress Response ◽  
Compound Heterozygous ◽  
Storage Material ◽  
Cellular Environment ◽  
And Oxidative Stress

AbstractInfantile Neuronal Ceroid Lipofuscinosis (INCL) is a pediatric neurodegenerative disorder characterized by progressive retinal and central nervous system deterioration during infancy. This lysosomal storage disorder results from a deficiency in the Palmitoyl Protein Thioesterase 1 (PPT1) enzyme - a lysosomal hydrolase which cleaves fatty acid chains such as palmitate from lipid-modified proteins. In the absence of PPT1 activity, these proteins fail to be degraded, leading to the accumulation of autofluorescence storage material in the lysosome. The underlying molecular mechanisms leading to INCL pathology remain poorly understood. A role for oxidative stress has been postulated, yet little evidence has been reported to support this possibility. Here we present a comprehensive cellular characterization of human PPT1-deficient fibroblast cells harboring Met1Ile and Tyr247His compound heterozygous mutations. We detected autofluorescence storage material and observed distinct organellar abnormalities of the lysosomal and mitochondrial structures, which supported previous postulations about the role of ER, mitochondria and oxidative stress in INCL. An increase in the number of lysosomal structures was found in INCL patient fibroblasts, which suggested an upregulation of lysosomal biogenesis, and an association with endoplasmic reticulum stress response. The mitochondrial network also displayed abnormal spherical punctate morphology instead of normal elongated tubules with extensive branching, supporting the involvement of mitochondrial and oxidative stress in INCL cell death. Autofluorescence accumulation and lysosomal pathologies can be mitigated in the presence of conditioned wild type media suggesting that a partial restoration via passive introduction of the enzyme into the cellular environment may be possible. We also demonstrated, for the first time, that human INCL fibroblasts have a heightened susceptibility to exogenous reactive oxygen species (ROS)-induced cell death, which suggested an elevated basal level of endogenous ROS in the mutant cell. Collectively, these findings support the role of intracellular organellar networks in INCL pathology, possibly due to oxidative stress.

Cadmium toxicity in cultured tomato cells-Role of ethylene, proteases and oxidative stress in cell death signaling

2008 ◽  
Vol 32 (12) ◽  
pp. 1521-1529 ◽  
Author(s):  
Elena T. Iakimova ◽  
Ernst J. Woltering ◽  
Veneta M. Kapchina-Toteva ◽  
Frans J.M. Harren ◽  
Simona M. Cristescu
Keyword(s):  
Oxidative Stress ◽  
Cell Death ◽  
Cadmium Toxicity ◽  
Cell Death Signaling ◽  
And Oxidative Stress

scholarly journals Ethanol-Induced Oxidative Stress Modifies Inflammation and Angiogenesis Biomarkers in Retinal Pigment Epithelial Cells (ARPE-19): Role of CYP2E1 and its Inhibition by Antioxidants

Antioxidants ◽  
2020 ◽  
Vol 9 (9) ◽  
pp. 776
Author(s):  
Natalia Martinez-Gil ◽  
Lorena Vidal-Gil ◽  
Miguel Flores-Bellver ◽  
Rosa Maisto ◽  
Javier Sancho-Pelluz ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Cell Death ◽  
Retinal Pigment Epithelial ◽  
Pigment Epithelium ◽  
Retinal Pigment ◽  
Retinal Pigment Epithelial Cells ◽  
Fluorescence Probes ◽  
And Oxidative Stress ◽  
Pigment Epithelial Cells

The retinal pigment epithelium (RPE) plays a key role in retinal health, being essential for the protection against reactive oxygen species (ROS). Nevertheless, excessive oxidative stress can induce RPE dysfunction, promoting visual loss. Our aim is to clarify the possible implication of CYP2E1 in ethanol (EtOH)-induced oxidative stress in RPE alterations. Despite the increase in the levels of ROS, measured by fluorescence probes, the RPE cells exposed to the lowest EtOH concentrations were able to maintain cell survival, measured by the Cell Proliferation Kit II (XTT). However, EtOH-induced oxidative stress modified inflammation and angiogenesis biomarkers, analyzed by proteome array, ELISA, qPCR and Western blot. The highest EtOH concentration used stimulated a large increase in ROS levels, upregulating the cytochrome P450-2E1 (CYP2E1) and promoting cell death. The use of antioxidants such as N-acetylcysteine (NAC) and diallyl sulfide (DAS), which is also a CYP2E1 inhibitor, reverted cell death and oxidative stress, modulating also the upstream angiogenesis and inflammation regulators. Because oxidative stress plays a central role in most frequent ocular diseases, the results herein support the proposal that CYP2E1 upregulation could aggravate retinal degeneration, especially in those patients with high baseline oxidative stress levels due to their ocular pathology and should be considered as a risk factor.

scholarly journals Ferroptosis Holds Novel Promise in Treatment of Cancer Mediated by Non-coding RNAs

2021 ◽  
Vol 9 ◽  
Author(s):  
Yuan Zhi ◽  
Ling Gao ◽  
Baisheng Wang ◽  
Wenhao Ren ◽  
Kristina Xiao Liang ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Cell Death ◽  
Physiological Mechanism ◽  
Cancer Therapeutics ◽  
Molecular Regulation ◽  
Circular Rnas ◽  
Regulated Cell Death ◽  
Non Coding Rnas ◽  
And Oxidative Stress

Ferroptosis is a newly identified form of regulated cell death that is associated with iron metabolism and oxidative stress. As a physiological mechanism, ferroptosis selectively removes cancer cells by regulating the expression of vital chemical molecules. Current findings on regulation of ferroptosis have largely focused on the function of non-coding RNAs (ncRNAs), especially microRNAs (miRNAs), in mediating ferroptotic cell death, while the sponging effect of circular RNAs (circRNAs) has not been widely studied. In this review, we discuss the molecular regulation of ferroptosis and highlight the value of circRNAs in controlling ferroptosis and carcinogenesis. Herein, we deliberate future role of this emerging form of regulated cell death in cancer therapeutics and predict the progression and prognosis of oncogenesis in future clinical therapy.

scholarly journals Human INCL fibroblasts display abnormal mitochondrial and lysosomal networks and heightened susceptibility to ROS-induced cell death

PLoS ONE ◽  
2021 ◽  
Vol 16 (2) ◽  
pp. e0239689 ◽  
Author(s):  
Bailey Balouch ◽  
Halle Nagorsky ◽  
Truc Pham ◽  
James Thai LaGraff ◽  
Quynh Chu-LaGraff
Keyword(s):  
Oxidative Stress ◽  
Cell Death ◽  
Molecular Mechanisms ◽  
Neurodegenerative Disorder ◽  
Endoplasmic Reticulum Stress Response ◽  
Compound Heterozygous ◽  
Storage Material ◽  
Cellular Environment ◽  
And Oxidative Stress

Infantile Neuronal Ceroid Lipofuscinosis (INCL) is a pediatric neurodegenerative disorder characterized by progressive retinal and central nervous system deterioration during infancy. This lysosomal storage disorder results from a deficiency in the Palmitoyl Protein Thioesterase 1 (PPT1) enzyme—a lysosomal hydrolase which cleaves fatty acid chains such as palmitate from lipid-modified proteins. In the absence of PPT1 activity, these proteins fail to be degraded, leading to the accumulation of autofluorescence storage material in the lysosome. The underlying molecular mechanisms leading to INCL pathology remain poorly understood. A role for oxidative stress has been postulated, yet little evidence has been reported to support this possibility. Here we present a comprehensive cellular characterization of human PPT1-deficient fibroblast cells harboring Met1Ile and Tyr247His compound heterozygous mutations. We detected autofluorescence storage material and observed distinct organellar abnormalities of the lysosomal and mitochondrial structures, which supported previous postulations about the role of ER, mitochondria and oxidative stress in INCL. An increase in the number of lysosomal structures was found in INCL patient fibroblasts, which suggested an upregulation of lysosomal biogenesis, and an association with endoplasmic reticulum stress response. The mitochondrial network also displayed abnormal spherical punctate morphology instead of normal elongated tubules with extensive branching, supporting the involvement of mitochondrial and oxidative stress in INCL cell death. Autofluorescence accumulation and lysosomal pathologies can be mitigated in the presence of conditioned wild type media suggesting that a partial restoration via passive introduction of the enzyme into the cellular environment may be possible. We also demonstrated, for the first time, that human INCL fibroblasts have a heightened susceptibility to exogenous reactive oxygen species (ROS)-induced cell death, which suggested an elevated basal level of endogenous ROS in the mutant cell. Collectively, these findings support the role of intracellular organellar networks in INCL pathology, possibly due to oxidative stress.

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