scholarly journals Conjugation of Natural Triterpenic Acids with Delocalized Lipophilic Cations: Selective Targeting Cancer Cell Mitochondria

2021 ◽  
Vol 11 (6) ◽  
pp. 470
Author(s):  
Anna Yu. Spivak ◽  
Darya A. Nedopekina ◽  
Rinat R. Gubaidullin ◽  
Mikhail V. Dubinin ◽  
Konstantin N. Belosludtsev
Keyword(s):  
Reactive Oxygen Species ◽  
Anticancer Agents ◽  
Energy Production ◽  
Reactive Oxygen ◽  
Oxygen Species ◽  
Pentacyclic Triterpenoids ◽  
Cell Death Pathways ◽  
Selective Targeting ◽  
Triterpenic Acids ◽  
Distinguishing Features

Currently, a new line of research on mitochondria-targeted anticancer drugs is actively developing in the field of biomedicine and medicinal chemistry. The distinguishing features of this universal target for anticancer agents include presence of mitochondria in the overwhelming majority, if not all types of transformed cells, crucial importance of these cytoplasmic organelles in energy production, regulation of cell death pathways, as well as generation of reactive oxygen species and maintenance of calcium homeostasis. Hence, mitochondriotropic anticancer mitocan agents, acting through mitochondrial destabilization, have good prospects in cancer therapy. Available natural pentacyclic triterpenoids are considered promising scaffolds for development of new mitochondria-targeted anticancer agents. These secondary metabolites affect the mitochondria of tumor cells and initiate formation of reactive oxygen species. The present paper focuses on the latest research outcomes of synthesis and study of cytotoxic activity of conjugates of pentacyclic triterpenoids with some mitochondria-targeted cationic lipophilic molecules and highlights the advantages of applying them as novel mitocan agents compared to their prototype natural triterpenic acids.

scholarly journals OTUD1 deubiquitylase regulates NF-κB- and KEAP1-mediated inflammatory responses and reactive oxygen species-associated cell death pathways

2021 ◽  
Author(s):  
Daisuke Oikawa ◽  
Min Gi ◽  
Hidetaka Kosako ◽  
Kouhei Shimizu ◽  
Hirotaka Takahashi ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Cell Death ◽  
Stress Responses ◽  
Inflammatory Responses ◽  
Reactive Oxygen ◽  
Antioxidant Response ◽  
Oxygen Species ◽  
Ubiquitin Chain ◽  
Intrinsically Disordered ◽  
Cell Death Pathways

Deubiquitylating enzymes (DUBs) regulate numerous cellular functions by removing ubiquitin modifications. We examined the effects of 88 human DUBs on linear ubiquitin chain assembly complex (LUBAC)-induced NF-κB activation, and identified OTUD1 as a potent suppressor. OTUD1 regulates the canonical NF-κB pathway by hydrolysing K63-linked ubiquitin chains from NF-κB signalling factors, including LUBAC. OTUD1 negatively regulates the canonical NF-κB activation, apoptosis, and necroptosis, whereas OTUD1 upregulates the interferon (IFN) antiviral pathway. The N-terminal intrinsically disordered region of OTUD1, which contains an EGTE motif, is indispensable for KEAP1-binding and NF-κB suppression. OTUD1 is involved in the KEAP1-mediated antioxidant response and reactive oxygen species (ROS)-induced cell death, oxeiptosis. In Otud1-/--mice, inflammation, oxidative damage, and cell death were enhanced in inflammatory bowel disease, acute hepatitis, and sepsis models. Thus, OTUD1 is a crucial regulator for the inflammatory, innate immune, and oxidative stress responses and ROS-associated cell death pathways.

scholarly journals Role of Mitochondrial Calcium and the Permeability Transition Pore in Regulating Cell Death

2020 ◽  
Vol 126 (2) ◽  
pp. 280-293 ◽  
Author(s):  
Tyler M. Bauer ◽  
Elizabeth Murphy
Keyword(s):  
Reactive Oxygen Species ◽  
Cell Death ◽  
Reactive Oxygen ◽  
Permeability Transition Pore ◽  
Permeability Transition ◽  
Mitochondrial Calcium ◽  
Oxygen Species ◽  
Inner Mitochondrial Membrane ◽  
Atp Production ◽  
Cell Death Pathways

Adult cardiomyocytes are postmitotic cells that undergo very limited cell division. Thus, cardiomyocyte death as occurs during myocardial infarction has very detrimental consequences for the heart. Mitochondria have emerged as an important regulator of cardiovascular health and disease. Mitochondria are well established as bioenergetic hubs for generating ATP but have also been shown to regulate cell death pathways. Indeed many of the same signals used to regulate metabolism and ATP production, such as calcium and reactive oxygen species, are also key regulators of mitochondrial cell death pathways. It is widely hypothesized that an increase in calcium and reactive oxygen species activate a large conductance channel in the inner mitochondrial membrane known as the PTP (permeability transition pore) and that opening of this pore leads to necroptosis, a regulated form of necrotic cell death. Strategies to reduce PTP opening either by inhibition of PTP or inhibiting the rise in mitochondrial calcium or reactive oxygen species that activate PTP have been proposed. A major limitation of inhibiting the PTP is the lack of knowledge about the identity of the protein(s) that form the PTP and how they are activated by calcium and reactive oxygen species. This review will critically evaluate the candidates for the pore-forming unit of the PTP and discuss recent data suggesting that assumption that the PTP is formed by a single molecular identity may need to be reconsidered.

Holographic monitoring of cell death pathways induced by reactive oxygen species

2018 ◽  
Author(s):  
A.V. Belashov ◽  
A.A. Zhikhoreva ◽  
D.A. Rogova ◽  
T.N. Belyaeva ◽  
E.S. Kornilova ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Cell Death ◽  
Reactive Oxygen ◽  
Oxygen Species ◽  
Cell Death Pathways

scholarly journals Mechanism of Action of Phenethylisothiocyanate and Other Reactive Oxygen Species-Inducing Anticancer Agents

2014 ◽  
Vol 34 (13) ◽  
pp. 2382-2395 ◽  
Author(s):  
I. Jutooru ◽  
A. S. Guthrie ◽  
G. Chadalapaka ◽  
S. Pathi ◽  
K. Kim ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Mechanism Of Action ◽  
Anticancer Agents ◽  
Reactive Oxygen ◽  
Oxygen Species

scholarly journals Unifying Mechanism for Nutrients as Anticancer Agents: Electron Transfer, Reactive Oxygen Species and Oxidative Stress

2017 ◽  
Vol 9 (8) ◽  
pp. 66 ◽  
Author(s):  
Peter Kovacic ◽  
Ratnasamy Somanathan
Keyword(s):  
Oxidative Stress ◽  
Reactive Oxygen Species ◽  
Electron Transfer ◽  
Anticancer Agents ◽  
Mode Of Action ◽  
Recent Article ◽  
Reactive Oxygen ◽  
Oxygen Species ◽  
Bactericidal Action ◽  
And Oxidative Stress

A recent article deals with various nutrients in relation to bactericidal action. The present article focuses on a unifying mode of action for the nutrients, namely, resveratrol, epigallocatechin, polyene-ß-carotene, polyene lycopene, piperine, curcumin, genistein, luteolin, sulforaphane and pomegranate extract. The mechanism is based on electron transfer, reactive oxygen species and oxidative stress, which comprises an extension of earlier reports involving agents. Most of the compounds are precursors of electron transfer quinones, whereas others fit into the polyene category. The nutrients are better known as antioxidants. The dichotomy is addressed.

scholarly journals Mitochondrial Management of Reactive Oxygen Species

Antioxidants ◽  
2021 ◽  
Vol 10 (11) ◽  
pp. 1824
Author(s):  
Gaetana Napolitano ◽  
Gianluca Fasciolo ◽  
Paola Venditti
Keyword(s):  
Reactive Oxygen Species ◽  
Antioxidant System ◽  
Energy Production ◽  
Krebs Cycle ◽  
Reactive Oxygen ◽  
Biological Molecules ◽  
Oxygen Species ◽  
Primary Target ◽  
Cellular Compartments ◽  
Harmful Species

Mitochondria in aerobic eukaryotic cells are both the site of energy production and the formation of harmful species, such as radicals and other reactive oxygen species, known as ROS. They contain an efficient antioxidant system, including low-molecular-mass molecules and enzymes that specialize in removing various types of ROS or repairing the oxidative damage of biological molecules. Under normal conditions, ROS production is low, and mitochondria, which are their primary target, are slightly damaged in a similar way to other cellular compartments, since the ROS released by the mitochondria into the cytosol are negligible. As the mitochondrial generation of ROS increases, they can deactivate components of the respiratory chain and enzymes of the Krebs cycle, and mitochondria release a high amount of ROS that damage cellular structures. More recently, the feature of the mitochondrial antioxidant system, which does not specifically deal with intramitochondrial ROS, was discovered. Indeed, the mitochondrial antioxidant system detoxifies exogenous ROS species at the expense of reducing the equivalents generated in mitochondria. Thus, mitochondria are also a sink of ROS. These observations highlight the importance of the mitochondrial antioxidant system, which should be considered in our understanding of ROS-regulated processes. These processes include cell signaling and the progression of metabolic and neurodegenerative disease.

scholarly journals Considerations on the Ethiopathogenesis of Algae from the Primary Form of BMD

2019 ◽  
Vol 70 (7) ◽  
pp. 2425-2428
Author(s):  
Bogdan Ioan Coculescu ◽  
Gheorghe Manole ◽  
Valeriu-Gabi Dinca ◽  
Alexandra-Ligia Dinca ◽  
Elena Claudia Coculescu
Keyword(s):  
Reactive Oxygen Species ◽  
Energy Production ◽  
Reactive Oxygen ◽  
Burning Mouth Syndrome ◽  
Oxygen Species ◽  
Burning Mouth ◽  
Sensory Fibers ◽  
Primary Form

The study is motivated by the existence of a still controversial etiopathogen on Burning Mouth Syndrome. The objective of the study, which is carried out on a group of 103 sick of both sexes, presenting the Burning Mouth Disorder - the primary form, is to identify the prevalence of the disease and establish possible correlations with coexistence of age, gender and dyslipidemia as factors that can be considered as favoring the installation non-specific oral allergy. The conclusions of the research constitute an argument for admitting the hypothesis of the existence of a neuronal irrigation deficiency, manifested both at the conductive sensory fibers of the influx and, more preferably, at the sensory-sensorial cortex for pain and taste, or only at one of these levels. According to the hypothesis, neuronal suffering consists in a deficiency of energy production and use, induced by excessively local reactive oxygen species, through irrigation, developed by the presence of arteriosclerosis.

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