scholarly journals Nifedipine Modulates Renal Lipogenesis via the AMPK-SREBP Transcriptional Pathway

2019 ◽  
Vol 20 (7) ◽  
pp. 1570 ◽  
Author(s):  
Yen-Chung Lin ◽  
Mai-Szu Wu ◽  
Yuh-Feng Lin ◽  
Chang-Rong Chen ◽  
Chang-Yu Chen ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Lipid Accumulation ◽  
Coenzyme A ◽  
Surrogate Marker ◽  
Reactive Oxygen ◽  
Fatty Acyl ◽  
Acid Oxidation ◽  
Oxygen Species ◽  
Atp Production ◽  
Renal Tubular Cells

Lipid accumulation in renal cells has been implicated in the pathogenesis of obesity-related kidney disease, and lipotoxicity in the kidney can be a surrogate marker for renal failure or renal fibrosis. Fatty acid oxidation provides energy to renal tubular cells. Ca2+ is required for mitochondrial ATP production and to decrease reactive oxygen species (ROS). However, how nifedipine (a calcium channel blocker) affects lipogenesis is unknown. We utilized rat NRK52E cells pre-treated with varying concentrations of nifedipine to examine the activity of lipogenesis enzymes and lipotoxicity. A positive control exposed to oleic acid was used for comparison. Nifedipine was found to activate acetyl Coenzyme A (CoA) synthetase, acetyl CoA carboxylase, long chain fatty acyl CoA elongase, ATP-citrate lyase, and 3-hydroxy-3-methyl-glutaryl-coenzyme A (HMG CoA) reductase, suggesting elevated production of cholesterol and phospholipids. Nifedipine exposure induced a vast accumulation of cytosolic free fatty acids (FFA) and stimulated the production of reactive oxygen species, upregulated CD36 and KIM-1 (kidney injury molecule-1) expression, inhibited p-AMPK activity, and triggered the expression of SREBP-1/2 and lipin-1, underscoring the potential of nifedipine to induce lipotoxicity with renal damage. To our knowledge, this is the first report demonstrating nifedipine-induced lipid accumulation in the kidney.

scholarly journals Kinetic Modeling of the Mitochondrial Energy Metabolism of Neuronal Cells: The Impact of Reducedα-Ketoglutarate Dehydrogenase Activities on ATP Production and Generation of Reactive Oxygen Species

2012 ◽  
Vol 2012 ◽  
pp. 1-11 ◽  
Author(s):  
Nikolaus Berndt ◽  
Sascha Bulik ◽  
Hermann-Georg Holzhütter
Keyword(s):  
Reactive Oxygen Species ◽  
Neurodegenerative Diseases ◽  
Neuronal Cells ◽  
Reactive Oxygen ◽  
Oxygen Species ◽  
Mitochondrial Energy Metabolism ◽  
Atp Production ◽  
Dependent Inactivation ◽  
The Impact ◽  
Ketoglutarate Dehydrogenase

Reduced activity of brain α-ketoglutarate dehydrogenase complex (KGDHC) occurs in a number of neurodegenerative diseases like Parkinson's disease and Alzheimer's disease. In order to quantify the relation between diminished KGDHC activity and the mitochondrial ATP generation, redox state, transmembrane potential, and generation of reactive oxygen species (ROS) by the respiratory chain (RC), we developed a detailed kinetic model. Model simulations revealed a threshold-like decline of the ATP production rate at about 60% inhibition of KGDHC accompanied by a significant increase of the mitochondrial membrane potential. By contrast, progressive inhibition of the enzyme aconitase had only little impact on these mitochondrial parameters. As KGDHC is susceptible to ROS-dependent inactivation, we also investigated the reduction state of those sites of the RC proposed to be involved in ROS production. The reduction state of all sites except one decreased with increasing degree of KGDHC inhibition suggesting an ROS-reducing effect of KGDHC inhibition. Our model underpins the important role of reduced KGDHC activity in the energetic breakdown of neuronal cells during development of neurodegenerative diseases.

scholarly journals Lipid droplets alleviate cadmium induced cytotoxicity in Saccharomyces cerevisiae

2017 ◽  
Vol 6 (1) ◽  
pp. 30-41 ◽  
Author(s):  
Selvaraj Rajakumar ◽  
Vasanthi Nachiappan
Keyword(s):  
Oxidative Stress ◽  
Saccharomyces Cerevisiae ◽  
Reactive Oxygen Species ◽  
Lipid Accumulation ◽  
Lipid Droplets ◽  
Reactive Oxygen ◽  
Oxygen Species

Cadmium (Cd) induces oxidative stress that generates reactive oxygen species (ROS) and increased lipid accumulation.

scholarly journals Caffeic acid reduces lipid accumulation and reactive oxygen species production in adipocytes

2018 ◽  
Vol 12 (20) ◽  
pp. 263-268 ◽  
Author(s):  
Brito Dantas Mariana ◽  
Lima Sampaio Tiago ◽  
Róseo Paula Pessoa Bezerra de Menezes Ramon ◽  
Magalhães Ferreira Jamile ◽  
Sousa Melo Tiago ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Caffeic Acid ◽  
Lipid Accumulation ◽  
Reactive Oxygen Species Production ◽  
Reactive Oxygen ◽  
Oxygen Species ◽  
Species Production

scholarly journals LPS from P. gingivalis Negatively Alters Gingival Cell Mitochondrial Bioenergetics

2017 ◽  
Vol 2017 ◽  
pp. 1-6 ◽  
Author(s):  
Kiran Napa ◽  
Andrea C. Baeder ◽  
Jeffrey E. Witt ◽  
Sarah T. Rayburn ◽  
Madison G. Miller ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Reactive Oxygen Species ◽  
Mitochondrial Function ◽  
Reactive Oxygen Species Generation ◽  
Reactive Oxygen ◽  
Human Gingival Fibroblast ◽  
Gingival Fibroblast ◽  
Oxygen Species ◽  
Atp Production ◽  
Lps Treatment

Objective. Oral inflammatory pathologies are linked to increased oxidative stress, thereby partly explaining their relevance in the etiology of systemic disorders. The purpose of this work was to determine the degree to which LPS from Porphyromonas gingivalis, the primary pathogen related to oral inflammation, altered gingival mitochondrial function and reactive oxygen species generation. Methods. Human gingival fibroblast (HGF-1) cells were treated with lipopolysaccharide of P. gingivalis. Mitochondrial function was determined via high-resolution respirometry. Results. LPS-treated HGF-1 cells had significantly higher mitochondrial complex IV and higher rates of mitochondrial respiration. However, this failed to translate into greater ATP production, as ATP production was paradoxically diminished with LPS treatment. Nevertheless, production of the reactive H2O2 was elevated with LPS treatment. Conclusions. LPS elicits an increase in gingival cell mitochondria content, with a subsequent increase in reactive oxygen species production (i.e., H2O2), despite a paradoxical reduction in ATP generation. These findings provide an insight into the nature of oxidative stress in oral inflammatory pathologies.

Ginsenoside F1 attenuates lipid accumulation and triglycerides content in 3T3-L1 adipocytes with the modulation of reactive oxygen species (ROS) production through PPAR-γ/JAK2 signaling responses

2017 ◽  
Vol 26 (5) ◽  
pp. 1042-1051 ◽  
Author(s):  
Shakina Yesmin Simu ◽  
Muhammad Hanif Siddiqi ◽  
Sungeun Ahn ◽  
Verónica Castro-Aceituno ◽  
Natarajan Sathish Kumar ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Lipid Accumulation ◽  
Reactive Oxygen ◽  
Ros Production ◽  
Oxygen Species ◽  
Ppar Γ

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.

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