Oxidative Stress

Sies, Helmut; Berndt, Carsten; Jones, Dean P.

doi:10.1146/annurev-biochem-061516-045037

Cited by 2,636 publications

(2,078 citation statements)

References 215 publications

Supporting

Mentioning

2,004

Contrasting

Unclassified

Order By: Relevance

“…In humans, IL-18 blood levels increase with ageing, and strong evidence from mouse studies indicates that blockade of the NLRP3 inflammasome extends healthspan, attenuating multiple age-related degenerative changes that have been linked to inflammageing, including insulin resistance, thymic involution, T cell senescence, and bone loss as well as physical and cognitive function decline 114,117,118 . Of note, ROS produced by dysfunctional mitochondria can also trigger an inflammatory response by activating the NF-κB signalling pathway 119 .…”

Section: Risk Factors and Causes Of Inflammageingmentioning

confidence: 99%

Inflammageing: chronic inflammation in ageing, cardiovascular disease, and frailty

2018

View full text Add to dashboard Cite

Most older individuals develop inflammageing, a condition characterized by elevated levels of blood inflammatory markers that carries high susceptibility to chronic morbidity, disability, frailty, and premature death. Potential mechanisms of inflammageing include genetic susceptibility, central obesity, increased gut permeability, changes to microbiota composition, cellular senescence, NLRP3 inflammasome activation, oxidative stress caused by dysfunctional mitochondria, immune cell dysregulation, and chronic infections. Inflammageing is a risk factor for cardiovascular diseases (CVDs), and clinical trials suggest that this association is causal. Inflammageing is also a risk factor for chronic kidney disease, diabetes mellitus, cancer, depression, dementia, and sarcopenia, but whether modulating inflammation beneficially affects the clinical course of non-CVD health problems is controversial. This uncertainty is an important issue to address because older patients with CVD are often affected by multimorbidity and frailty — which affect clinical manifestations, prognosis, and response to treatment — and are associated with inflammation by mechanisms similar to those in CVD. The hypothesis that inflammation affects CVD, multimorbidity, and frailty by inhibiting growth factors, increasing catabolism, and interfering with homeostatic signalling is supported by mechanistic studies but requires confirmation in humans. Whether early modulation of inflammageing prevents or delays the onset of cardiovascular frailty should be tested in clinical trials.

show abstract

Section: Risk Factors and Causes Of Inflammageingmentioning

confidence: 99%

Inflammageing: chronic inflammation in ageing, cardiovascular disease, and frailty

2018

View full text Add to dashboard Cite

show abstract

“…These redox couples serve different functions, with NAD supporting catabolism and high-flux bioenergetic demands, and NADP supporting biosynthetic and detoxification activities. Conventions for expressing the reducing force of these couples in terms of steady-state redox potential (E h ) are considered elsewhere [7–9]; most critically, the NADP couple is maintained at a more negative potential (greater reducing force) to support biosynthetic and detoxification functions while the NAD couple is maintained at a more positive steady state to facilitate oxidation of metabolic fuels for ATP production by oxidative phosphorylation [10–12]. …”

Section: Mitochondrial Network and The Redox Codementioning

confidence: 99%

Mitochondrial network responses in oxidative physiology and disease

Fernandes

et al. 2018

Free Radical Biology and Medicine

Self Cite

View full text Add to dashboard Cite

Mitochondrial activities are linked directly or indirectly to all cellular functions in aerobic eukaryotes. Omics methods enable new approaches to study functional organization of mitochondria and their adaptive and maladaptive network responses to bioenergetic fuels, physiologic demands, environmental challenges and aging. In this review, we consider mitochondria collectively within a multicellular organism as a macroscale “mitochondriome”, functioning to organize bioenergetics and metabolism as an organism utilizes environmental resources and protects against environmental threats. We address complexities of knowledgebase-driven functional mapping of mitochondrial systems and then consider data-driven network mapping using omics methods. Transcriptome-metabolome-wide association study (TMWAS) shows connectivity and organization of nuclear transcription with mitochondrial transport systems in cellular responses to mitochondria-mediated toxicity. Integration of redox and respiratory measures with TMWAS shows central redox hubs separating systems linked to oxygen consumption rate and H2O2 production. Combined redox proteomics, metabolomics and transcriptomics further shows that physiologic network structures can be visualized separately from toxicologic networks. These data-driven integrated omics methods create new opportunities for mitochondrial systems biology.

show abstract

“…Excessive levels of ROS lead to detrimental reactions with proteins, nucleic acids and lipids, playing an indispensable role in various cellular processes, including cell life and death decisions [39]. It is now clear that when exposed to ultrasound, the porphyrin-based sensitizers generate ROS, causing cytotoxicity [40].…”

Section: Discussionmentioning

confidence: 99%

5-Aminolevulinic Acid-Mediated Sonodynamic Therapy Alleviates Atherosclerosis via Enhancing Efferocytosis and Facilitating a Shift in the Th1/Th2 Balance Toward Th2 Polarization

Yang

Liu

Chen

et al. 2018

Cell Physiol Biochem

View full text Add to dashboard Cite

Background/Aims: We and other groups have demonstrated that 5-aminolevulinic acid (ALA)-mediated sonodynamic therapy (ALA-SDT) induces macrophage and foam cell apoptosis and stabilizes atherosclerosis (AS) plaques in animal models. Lymphocytes also play vital roles in the development of AS. The primary purpose of the present study was to investigate the effects of ALA-SDT on T helper (Th) cell fate and function, Th subset differentiation, and atherosclerotic lesion stability. Methods: We utilized ALA-SDT on Western diet-fed apoE^-/-mice in vivo and human Jurkat cells in vitro. Hematoxylin and eosin staining and TUNEL assays were used to evaluate the atherosclerotic plaque size and apoptosis within the atheroma. ALA induced cytotoxicity on cultured Jurkat cells was determined with CCK-8 assay. To address the mechanisms, levels of intracellular reactive oxygen species (ROS), mitochondrial membrane potential (MMP), and mitochondrial permeability transition pore (MPTP) opening were evaluated by staining with fluorescent probes. Western blot analysis and confocal microscopy were used to analyze the protein levels of caspases, Bax and cytochrome c and the release of cytochrome c. Cell apoptosis and necrosis and phagocytosis were examined by flow cytometry. ELISAs and immunofluorescent staining were used to assess the corresponding cytokine levels and Th subset cell numbers within the atheroma. Results: Our studies revealed that ALA-SDT significantly enhanced CD4⁺ cell apoptosis and macrophage-mediated phagocytosis and hence reduced the necrotic core size. ALA-SDT activated the mitochondrial apoptotic signaling pathway with minimal necrosis in Jurkat cells. ALA-SDT inhibited the Th1 response and enhanced the Th2 response. These effects of ALA-SDT were mediated primarily through the generation of ROS. Conclusion: ALA-SDT alleviates AS by enhancing cytotoxic effects on Th cells, subsequently stimulating efferocytosis and facilitating a shift in the Th1/Th2 balance toward Th2 cells, a discovery that might help elucidate the mechanism underlying SDT as a potential treatment to prevent atherothrombotic events.

show abstract

Oxidative Stress

Cited by 2,636 publications

References 215 publications

Inflammageing: chronic inflammation in ageing, cardiovascular disease, and frailty

Inflammageing: chronic inflammation in ageing, cardiovascular disease, and frailty

Mitochondrial network responses in oxidative physiology and disease

5-Aminolevulinic Acid-Mediated Sonodynamic Therapy Alleviates Atherosclerosis via Enhancing Efferocytosis and Facilitating a Shift in the Th1/Th2 Balance Toward Th2 Polarization

Contact Info

Product

Resources

About