Search results for "MITOCHONDRION"

Gamma-lactone-Functionalized antitumoral acetogenins are the most potent inhibitors of mitochondrial complex I.

2001

To study the relevance of the terminal alpha,beta-unsaturated gamma-methyl-gamma-lactone moiety of the antitumoral acetogenins of Annonaceae for potent mitochondrial complex I inhibition, we have prepared a series of semisynthetic acetogenins with modifications only in this part of the molecule, from the natural rolliniastatin-1 (1) and cherimolin-1 (2). Some of the hydroxylated derivatives (1b, 1d and 1e) in addition to two infrequent natural beta-hydroxy gamma-methyl gamma-lactone acetogenins, laherradurin (3) and itrabin (4), are more potent complex I inhibitors than any other known compounds.

Methomyl analogues with increased biological activity towards F7T maize mitochondria

1987

Abstract Methomyl analogues were synthesized by substituting alkyl moieties (C 2 -C 21 ) in the place of the carbamic methyl. They were assayed on mitochondria isolated from male sterile (F 7 T) and male fertile (F 7 N) maize. They had no action on F 7 N mitochondria. The heptadecyl (C 17 ) and heneicosanyl (C 21 ) derivatives had no conspicuous effect on F 7 T mitochondria. By contrast, the ethyl, propyl, butyl, nonyl, tridecyl (C 13 ) and pentadecyl (C 15 ) derivatives had the same type of activity as Methomyl on F 7 T mitochondria, namely stimulation of NADH oxidation and inhibition of malate oxidation. Moreover, the concentration at which they were maximally effective decreased from 10 …

Antineoplastic Drug-Induced Cardiotoxicity: A Redox Perspective

2018

Antineoplastic drugs can be associated with several side effects, including cardiovascular toxicity (CTX). Biochemical studies have identified multiple mechanisms of CTX. Chemoterapeutic agents can alter redox homeostasis by increasing the production of reactive oxygen species (ROS) and reactive nitrogen species RNS. Cellular sources of ROS/RNS are cardiomyocytes, endothelial cells, stromal and inflammatory cells in the heart. Mitochondria, peroxisomes and other subcellular components are central hubs that control redox homeostasis. Mitochondria are central targets for antineoplastic drug-induced CTX. Understanding the mechanisms of CTX is fundamental for effective cardioprotection, without…

Autoimmunity and liver disease

1990

The role of mitochondrial transition pore, and its modulation, in traumatic brain injury and delayed neurodegeneration after TBI

2009

Following severe traumatic brain injury (TBI), a complex interplay of pathomechanism, such as exitotoxicity, oxidative stress, inflammatory events, and mitochondrial dysfunction occurs. This leads to a cascade of neuronal and axonal pathologies, which ultimately lead to axonal failure, neuronal energy metabolic failure, and neuronal death, which in turn determine patient outcome. For mild and moderate TBI, the pathomechanism is similar but much less frequent and ischemic cell death is unusual, except with mass lesions. Involvement of mitochondria in acute post-traumatic neurodegeneration has been extensively studied during the last decade, and there are a number of investigations implicatin…

Overexpression of Human and Fly Frataxins in Drosophila Provokes Deleterious Effects at Biochemical, Physiological and Developmental Levels

2011

10 pages, 5 figures. 21779322[PubMed] PMCID: PMC3136927

FP187MITOCHONDRIAL DYSFUNCTION INDUCED BY TENOFOVIR IN RENAL CELLS. POTENTIATION OF THE EFFECTS BY CO-STIMULATION WITH ANGIOTENSIN II

2015

Possible Mechanisms for Tumour Cell Sensitivity to TNF-a and Potential Therapeutic Applications

2001

TNF is a macrophage / monocyte-derived cytokine with cytostatic and cytotoxic anti-tumour activity. TNF-alpha can cause haemorrhagic necrosis and regression of experimental tumours. Nevertheless, the TNF-alpha doses required to cure tumour-bearing mice lead to injury of normal tissues and, eventually, may cause a lethal shock syndrome. This toxicity implies severe limitations for the therapeutic use of TNF-a. Reactive oxygen intermediates (ROIs) are involved in TNF-a-induced cell killing. Different studies are consistent with the hypothesis that tumour cell sensitivity to TNF-alpha is related to its capacity to buffer oxidative attack. Recently, we have demonstrated that the sensitivity of …

Direct Activation of Bax by p53 Mediates Mitochondrial Membrane Permeabilization and Apoptosis

2004

The tumor suppressor p53 exerts its anti-neoplastic activity primarily through the induction of apoptosis. We found that cytosolic localization of endogenous wild-type or trans-activation–deficient p53 was necessary and sufficient for apoptosis. p53 directly activated the proapoptotic Bcl-2protein Bax in the absence of other proteins to permeabilize mitochondria and engage the apoptotic program. p53 also released both proapoptotic multidomain proteins and BH3-only proteins [Proapoptotic Bcl-2family proteins that share only the third Bcl-2homology domain (BH3)] that were sequestered by Bcl-xL. The transcription-independent activation of Bax by p53 occurred with similar kinetics and concentra…

The experimental herbicide UKJ72J is an inhibitor of succinate oxidation in plant mitochondria

1983

not received UKJ72J Herbicide Thiopyrimidine Plant mitochondria Inhibitor Succinate oxidation