Increase in mitochondrial mass in human fibroblasts under oxidative stress and during replicative cell senescence

2002 ◽  
Vol 9 (6) ◽  
pp. 517-526 ◽  
Author(s):  
Hsin-Chen Lee ◽  
Pen-Hui Yin ◽  
Chin-Wen Chi ◽  
Yau-Huei Wei
Keyword(s):  
Oxidative Stress ◽  
Human Fibroblasts ◽  
Cell Senescence ◽  
Mitochondrial Mass

The pleiotropic effects of Prunus avium L. extract against oxidative stress on human fibroblasts. An in vitro approach

2021 ◽  
Author(s):  
Sophia Letsiou ◽  
Aggeliki Karamaouna ◽  
Ioannis Ganopoulos ◽  
Aliki Kapazoglou ◽  
Aliki Xanthopoulou ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Prunus Avium ◽  
Human Fibroblasts ◽  
Pleiotropic Effects ◽  
Prunus Avium L

Matrine Protects PC12 Cells Against Aβ25–35-Induced Cytotoxicity, Oxidative Stress, Inflammation, Neuronal Apoptosis and Cell Senescence

2021 ◽  
Vol 11 (9) ◽  
pp. 1691-1697
Author(s):  
Huanli Zhang ◽  
Zhen Zhang
Keyword(s):  
Oxidative Stress ◽  
Cell Viability ◽  
Pc12 Cells ◽  
Neuronal Apoptosis ◽  
Inflammatory Responses ◽  
Neuronal Damage ◽  
Cell Senescence ◽  
Tunel Staining ◽  
Elisa Assay ◽  
Amyloid A

Background and Objectives: Beta-amyloid (Aβ) has pivotal functions in the pathogenesis of Alzheimer’s Disease (AD). The main purpose of this study is to explore the protective role and possible mechanisms of matrine against Aβ25–35-induced neurotoxicity in PC12 cells. Materials and Methods: A vitro model that involved Aβ25–35-induced neuronal damage in PC12 cells was adopted in the present study. Cell viability and apoptosis of PC12 cells were determined by CCK-8 assay and TUNEL staining, respectively. Intracellular ROS levels were determined by DCFH-DA probe and levels of TNFα, IL-6 and IL-1β were assessed by ELISA assay. In addition, telomerase reverse transcriptase (TERT) levels were determined by ELISA assay and telomere lengths were examined by real-time quantitative PCR analysis to assess telomerase activities. Furthermore, vital proteins related to cell apoptosis and hallmarks of senescence were detected by western blot analysis. Results: Matrine (10, 20, 50 μg/ml) dose-dependently protected cell viability against Aβ25–35 cytotoxicity in PC12 cells. Meanwhile, matrine at 10, 20, 50 μg/ml markedly reduced ROS production and downregulated the levels of TNFα, IL-6 and IL-1β in Aβ25–35-injuried PC12 cells. The results also proved that matrine may restore telomerase activities and telomere lengths in Aβ25–35-injuried PC12 cells by inhibiting inflammatory responses and oxidative stress. Neuronal apoptosis induced by Aβ25–35 were reversed upon cotreatment with matrine. Moreover, matrine markedly mitigated Aβ25–35 induced cell senescence in a concentration-dependentmanner. Conclusion: Our findings demonstrated that matrine protected PC12 cells against Aβ25–35-induced cytotoxicity, oxidative stress, inflammation, neuronal apoptosis and cell senescence.

scholarly journals Inhibition of TLR4 Signaling Affects Mitochondrial Fitness Overcoming Bortezomib Resistance in Myeloma Plasma Cells

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 3073-3073
Author(s):  
Cesarina Giallongo ◽  
Daniele Tibullo ◽  
Giuseppina Camiolo ◽  
Fabrizio Puglisi ◽  
Daniela Cambria ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Er Stress ◽  
Mitochondrial Respiration ◽  
Research Funding ◽  
Mitochondrial Dynamics ◽  
Mitochondrial Depolarization ◽  
Tlr4 Signaling ◽  
Mitochondrial Mass ◽  
Atp Production ◽  
Inflammatory Microenvironment

BACKGROUND Multiple myeloma (MM) is a B-cell malignancy critically dependent for survival and proliferation on signals coming from its inflammatory microenvironment in which toll-like receptors (TLR) may be potential linking elements between inflammation and cancer. It has been recently demonstrated that TLR4 pathway provides a protective effect against bortezomib (BTZ)-induced endoplasmic reticulum (ER) stress and pre-treatment of MM cells with LPS significantly reduces BTZ-induced apoptosis. AIM Since the acquisition of BTZ resistance is accompanied by an increased reliance on mitochondrial respiration, we investigated the role of TLR4 as stress-responsive mechanism that protect mitochondria during BTZ-induced ER stress as potential mechanism of drug resistance. RESULTS The activation of TLR4 signaling by LPS increased mitochondrial mass in human MM cell lines (HMCL: U266, MM1.S, OPM2, NCI-H929) and induced up-regulation of mitochondrial biogenesis markers (PGC1a, PRC and TFAM). After treatment with BTZ for 24h, all HMCL over-expressed TLR4 and its signaling was functional as suggested by up-regulation of MyD88 and MAPK activation. Compared to BTZ-sensitive cells (U266-S), U266-R showed higher levels of TLR4, p-p38 and p-ERK proteins and higher mitochondrial mass. Using a selective TLR4 inhibitor (TAK-242), we next treated U266-R cells with either 15nM BTZ, 20 μM TAK-242 or their combination. Combinatorial treatment significantly induced cell apoptosis (about 52%; p<0.001) that appeared to result from the deleterious effects of oxidative stress. Indeed, BTZ-induced intracellular ROS returned to normal levels after 3h and cells were able to up-regulate two anti-oxidant enzymes (GPX1 and GSTP1). On the contrary, TAK-242/BTZ activated a strong pro-oxidant status incresing ROS and RNS (reactive nitrogen species) levels, decreasing GSH ones and down-regulating GPX1 and GSTP1. Analyzing the effect of each treatment on mitochondrial polarization status, we observed about 6,7% of depolarized mitochondria after BTZ treatment, while TAK-242/BTZ combination induced a mitochondrial depolarization of about 69,3% (p<0.001). Moreover, cells treated with BTZ alone showed a compensatory up-regulation of the OXPHOS- (NDUFA-6 and MT-ND4) and mitochondrial fusion-related genes (mitofusin and OPA1) and TFAM. On the contrary, all these genes were down-regulated by TAK-242/BTZ combination. Also a dramatic drop in mitochondrial respiration was observed with a marked decrease in ATP production, consequent accumulation of AMP and a decreased NAD+/NADH and NADP+/NADPH ratio. Since high levels of oxidative stress and mitochondrial impairment activate mitophagy sensitizing cells to apoptosis, we evaluated co-localization of mitochondria (stained with MitoTracker) with the autophagosome marker LC3 using confocal microscopy. BTZ and TAK-242/BTZ increased Mitotracker/LC3 co-localization respectively of about 4,5 and 50 fold compared with control (BTZ vs combination: p<0.001). To evaluate whether TLR4 inhibition resensitizes resistant primary cells, CD138+ cells derived from 5 refractory/relapsed MM patients were treated with 5nM BTZ, 10mM TAK-242 or their combination. Compared to BTZ alone, combination treatment induced higher mitochondrial depolarization after 24h and significantly decreased viability of CD138+ cells after 48h. TLR4 inhibitor alone or in combination did never show cytotoxicity toward CD138- cells. CONCLUSION Taken together, these findings indicate thatTLR4 signaling is involved in the acquisition of bortezomib resistance protecting mitochondria during BTZ exposure and sustaining mitochondrial dynamics in BTZ-resitant cells. Inhibition of TLR4 may overcome bortezomib resistance in patients with relapsed/refractory MM. Disclosures Conticello: Celgene: Consultancy, Honoraria, Research Funding; Amgen: Consultancy, Honoraria, Research Funding. Palumbo:Celgene: Honoraria; Amgen: Honoraria; Hospira: Honoraria; Teva: Honoraria; Novartis: Honoraria; Janssen: Honoraria. Di Raimondo:Takeda: Consultancy; Amgen: Consultancy, Honoraria, Research Funding; Celgene: Consultancy, Honoraria, Research Funding.

Epicatechin and its in vivo metabolite, 3′-O-methyl epicatechin, protect human fibroblasts from oxidative-stress-induced cell death involving caspase-3 activation

2001 ◽  
Vol 354 (3) ◽  
pp. 493-500 ◽  
Author(s):  
Jeremy P. E. SPENCER ◽  
Hagen SCHROETER ◽  
Gunter KUHNLE ◽  
S. Kaila S. SRAI ◽  
Rex M. TYRRELL ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Hydrogen Peroxide ◽  
Cell Death ◽  
Caspase 3 ◽  
Cell Damage ◽  
Protective Action ◽  
Human Fibroblasts ◽  
Membrane Damage ◽  
Antioxidant Properties

There is considerable current interest in the cytoprotective effects of natural antioxidants against oxidative stress. In particular, epicatechin, a major member of the flavanol family of polyphenols with powerful antioxidant properties in vitro, has been investigated to determine its ability to attenuate oxidative-stress-induced cell damage and to understand the mechanism of its protective action. We have induced oxidative stress in cultured human fibroblasts using hydrogen peroxide and examined the cellular responses in the form of mitochondrial function, cell-membrane damage, annexin-V binding and caspase-3 activation. Since one of the major metabolites of epicatechin in vivo is 3′-O-methyl epicatechin, we have compared its protective effects with that of epicatechin. The results provide the first evidence that 3′-O-methyl epicatechin inhibits cell death induced by hydrogen peroxide and that the mechanism involves suppression of caspase-3 activity as a marker for apoptosis. Furthermore, the protection elicited by 3′-O-methyl epicatechin is not significantly different from that of epicatechin, suggesting that hydrogen-donating antioxidant activity is not the primary mechanism of protection.

scholarly journals Bradykinin Protects Against Oxidative Stress–Induced Endothelial Cell Senescence

Hypertension ◽  
2009 ◽  
Vol 53 (2) ◽  
pp. 417-422 ◽  
Author(s):  
Hisko Oeseburg ◽  
Dilek Iusuf ◽  
Pim van der Harst ◽  
Wiek H. van Gilst ◽  
Robert H. Henning ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Endothelial Cell ◽  
Cell Senescence

Human 8-Oxoguanine DNA Glycosylase Suppresses the Oxidative Stress–Induced Apoptosis through a p53-Mediated Signaling Pathway in Human Fibroblasts

2007 ◽  
Vol 5 (10) ◽  
pp. 1083-1098 ◽  
Author(s):  
Cha-Kyung Youn ◽  
Peter I. Song ◽  
Mi-Hwa Kim ◽  
Jin Sook Kim ◽  
Jin-Won Hyun ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Signaling Pathway ◽  
Human Fibroblasts ◽  
Dna Glycosylase ◽  
Induced Apoptosis

scholarly journals Effects of GH/IGF on the Aging Mitochondria

Cells ◽  
2020 ◽  
Vol 9 (6) ◽  
pp. 1384 ◽  
Author(s):  
Sher Bahadur Poudel ◽  
Manisha Dixit ◽  
Maria Neginskaya ◽  
Karthik Nagaraj ◽  
Evgeny Pavlov ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Growth Hormone ◽  
Cell Differentiation ◽  
Growth Factor ◽  
Mitochondrial Biogenesis ◽  
Mitochondrial Function ◽  
Cellular Aging ◽  
Mitochondrial Mass ◽  
Atp Production ◽  
And Function

The mitochondria are key organelles regulating vital processes in the eukaryote cell. A decline in mitochondrial function is one of the hallmarks of aging. Growth hormone (GH) and the insulin-like growth factor-1 (IGF-1) are somatotropic hormones that regulate cellular homeostasis and play significant roles in cell differentiation, function, and survival. In mammals, these hormones peak during puberty and decline gradually during adulthood and aging. Here, we review the evidence that GH and IGF-1 regulate mitochondrial mass and function and contribute to specific processes of cellular aging. Specifically, we discuss the contribution of GH and IGF-1 to mitochondrial biogenesis, respiration and ATP production, oxidative stress, senescence, and apoptosis. Particular emphasis was placed on how these pathways intersect during aging.

scholarly journals Administration of Enalapril Started Late in Life Attenuates Hypertrophy and Oxidative Stress Burden, Increases Mitochondrial Mass, and Modulates Mitochondrial Quality Control Signaling in the Rat Heart

Biomolecules ◽  
2018 ◽  
Vol 8 (4) ◽  
pp. 177 ◽  
Author(s):  
Anna Picca ◽  
Giuseppe Sirago ◽  
Vito Pesce ◽  
Angela Maria Serena Lezza ◽  
Riccardo Calvani ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Quality Control ◽  
Transcription Factor ◽  
Oxidative Damage ◽  
Mitochondrial Quality Control ◽  
Mitochondrial Transcription ◽  
Mitochondrial Mass ◽  
Mitochondrial Transcription Factor ◽  
Mitochondrial Transcription Factor A ◽  
And Oxidative Stress

Mitochondrial dysfunction is a relevant mechanism in cardiac aging. Here, we investigated the effects of late-life enalapril administration at a non-antihypertensive dose on mitochondrial genomic stability, oxidative damage, and mitochondrial quality control (MQC) signaling in the hearts of aged rats. The protein expression of selected mediators (i.e., mitochondrial antioxidant enzymes, energy metabolism, mitochondrial biogenesis, dynamics, and autophagy) was measured in old rats randomly assigned to receive enalapril (n = 8) or placebo (n = 8) from 24 to 27 months of age. We also assessed mitochondrial DNA (mtDNA) content, citrate synthase activity, oxidative lesions to protein and mtDNA (i.e., carbonyls and the abundance of mtDNA4834 deletion), and the mitochondrial transcription factor A (TFAM) binding to specific mtDNA regions. Enalapril attenuated cardiac hypertrophy and oxidative stress-derived damage (mtDNA oxidation, mtDNA4834 deletion, and protein carbonylation), while increasing mitochondrial antioxidant defenses. The binding of mitochondrial transcription factor A to mtDNA regions involved in replication and deletion generation was enhanced following enalapril administration. Increased mitochondrial mass as well as mitochondriogenesis and autophagy signaling were found in enalapril-treated rats. Late-life enalapril administration mitigates age-dependent cardiac hypertrophy and oxidative damage, while increasing mitochondrial mass and modulating MQC signaling. Further analyses are needed to conclusively establish whether enalapril may offer cardioprotection during aging.

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