scholarly journals Mitochondrial Dysfunction Is Involved in Apoptosis Induced by Serum Withdrawal and Fatty Acids in the β-Cell Line Ins-1

Endocrinology ◽  
2003 ◽  
Vol 144 (1) ◽  
pp. 335-345 ◽  
Author(s):  
Isabel Maestre ◽  
Joaquín Jordán ◽  
Soledad Calvo ◽  
Juan Antonio Reig ◽  
Valentín Ceña ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Nitric Oxide ◽  
Fatty Acids ◽  
Cytochrome C ◽  
Mitochondrial Function ◽  
Marginal Effect ◽  
Β Cell ◽  
Apoptosis Process ◽  
Apoptosis Inducing Factor ◽  
Factor Release

Abstract The potential toxic effects of high extracellular concentrations of fatty acids were tested in β(INS-1)-cells cultured in the absence of serum, a condition known to alter cell survival in various systems. This may in part mimic the situation in type 1 or 2 diabetes where β-cells are already insulted by various stressful conditions, such as cytokines and oxidative stress. Serum removal caused, over a 36-h period, oxidative stress and an early impairment of mitochondrial function, as revealed by increased superoxide production and markedly reduced mitochondrial membrane potential, but a lack of cytochrome c and apoptosis-inducing factor release in the cytosol. The fatty acids palmitate and oleate considerably accelerated the apoptosis process in serum-starved cells, as revealed by fluorescence-activated cell sorting analysis, morphological changes, chromatin condensation, DNA laddering, poly(ADP-ribose) polymerase cleavage, cytochrome c and apoptosis-inducing factor release, and increased levels of Bax and cytosolic caspase-2. The fatty acids also increased nitric oxide production, apparently independently of inducible nitric oxide synthase induction. Under the same experimental conditions, elevated glucose alone had only a marginal effect on β-cell apoptosis. Together the results indicate that elevated concentrations of fatty acids are particularly efficient in accelerating the rate of apoptosis of already stressed β(INS-1)-cells displaying altered mitochondrial function, and that the mitochondrial arm of the apoptosis process is involved in β-cell lipotoxicity.

scholarly journals Lipotoxic Impairment of Mitochondrial Function in β-Cells: A Review

Antioxidants ◽  
2021 ◽  
Vol 10 (2) ◽  
pp. 293
Author(s):  
Axel Römer ◽  
Thomas Linn ◽  
Sebastian F. Petry
Keyword(s):  
Oxidative Stress ◽  
Fatty Acids ◽  
Mitochondrial Dysfunction ◽  
Cellular Senescence ◽  
Cell Function ◽  
Radical Scavenging ◽  
Mitogen Activated Protein Kinase ◽  
Β Cells ◽  
Β Cell ◽  
Positive Effects

Lipotoxicity is a major contributor to type 2 diabetes mainly promoting mitochondrial dysfunction. Lipotoxic stress is mediated by elevated levels of free fatty acids through various mechanisms and pathways. Impaired peroxisome proliferator-activated receptor (PPAR) signaling, enhanced oxidative stress levels, and uncoupling of the respiratory chain result in ATP deficiency, while β-cell viability can be severely impaired by lipotoxic modulation of PI3K/Akt and mitogen-activated protein kinase (MAPK)/extracellular-signal-regulated kinase (ERK) pathways. However, fatty acids are physiologically required for an unimpaired β-cell function. Thus, preparation, concentration, and treatment duration determine whether the outcome is beneficial or detrimental when fatty acids are employed in experimental setups. Further, ageing is a crucial contributor to β-cell decay. Cellular senescence is connected to loss of function in β-cells and can further be promoted by lipotoxicity. The potential benefit of nutrients has been broadly investigated, and particularly polyphenols were shown to be protective against both lipotoxicity and cellular senescence, maintaining the physiology of β-cells. Positive effects on blood glucose regulation, mitigation of oxidative stress by radical scavenging properties or regulation of antioxidative enzymes, and modulation of apoptotic factors were reported. This review summarizes the significance of lipotoxicity and cellular senescence for mitochondrial dysfunction in the pancreatic β-cell and outlines potential beneficial effects of plant-based nutrients by the example of polyphenols.

scholarly journals SGK1 Attenuates Oxidative Stress-Induced Renal Tubular Epithelial Cell Injury by Regulating Mitochondrial Function

2019 ◽  
Vol 2019 ◽  
pp. 1-12 ◽  
Author(s):  
Daofang Jiang ◽  
Chensheng Fu ◽  
Jing Xiao ◽  
Zhenxing Zhang ◽  
Jianan Zou ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Membrane Potential ◽  
Cytochrome C ◽  
Cell Viability ◽  
Mitochondrial Biogenesis ◽  
Mitochondrial Function ◽  
Mitochondrial Membrane ◽  
Stress Injury ◽  
Oxidative Stress Injury ◽  
Renal Tubular

Mitochondrial dysfunction has been implicated in the early stages or progression of many renal diseases. Improving mitochondrial function and homeostasis has the potential to protect renal function. Serum- and glucocorticoid-induced kinase 1 (SGK1) is known to regulate various cellular processes, including cell survival. In this study, we intend to demonstrate the effect and molecular mechanisms of SGK1 in renal tubular cells upon oxidative stress injury and to determine whether regulation of mitochondrial function is implicated in this process. HK-2 cells were exposed to H2O2, and cell viability and apoptosis were dynamically detected by the CCK-8 assay and annexin-V/PI staining. The concentrations of cellular reactive oxygen species (ROS) and adenosine triphosphate (ATP) and the expression of the SGK1/GSK3β/PGC-1α signaling pathway were analyzed by flow cytometry or western blot. In addition, shRNA targeting SGK1 and SB216763 were added into the culture medium before H2O2 exposure to downregulate SGK1 and GSK3β, respectively. Cell viability and mitochondrial functions, including mitochondrial membrane potential (Δψm), Cytochrome C release, mtDNA copy number, and mitochondrial biogenesis, were examined. Protein levels and SGK1 activation were significantly stimulated by H2O2 exposure. HK-2 cells with SGK1 inhibition were much more sensitive to H2O2-induced oxidative stress injury than control group cells, as they exhibited increased apoptotic cell death and mitochondrial dysfunction involving the deterioration of cellular ATP production, ROS accumulation, mitochondrial membrane potential reduction, and release of Cytochrome C into the cytoplasm. Studies on SGK1 knockdown also indicated that SGK1 is required for the induction of proteins associated with mitochondrial biogenesis, including PGC-1α, NRF-1, and TFAM. Moreover, the deleterious effects of SGK1 suppression on cell apoptosis and mitochondrial function, including mitochondrial biogenesis, were related to the phosphorylation of GSK3β and partially reversed by SB216763 treatment. H2O2 leads to SGK1 overexpression in HK-2 cells, which protects human renal tubule cells from oxidative stress injury by improving mitochondrial function and inactivating GSK3β.

Arachidonic acid, palmitic acid and glucose are important for the modulation of clonal pancreatic β-cell insulin secretion, growth and functional integrity

2004 ◽  
Vol 106 (2) ◽  
pp. 191-199 ◽  
Author(s):  
Gordon DIXON ◽  
John NOLAN ◽  
Neville H. McCLENAGHAN ◽  
Peter R. FLATT ◽  
Philip NEWSHOLME
Keyword(s):  
Nitric Oxide ◽  
Fatty Acids ◽  
Cell Proliferation ◽  
Arachidonic Acid ◽  
Insulin Secretion ◽  
Type Ii Diabetes ◽  
Cell Mass ◽  
Type Ii ◽  
Β Cells ◽  
Β Cell

Insulin-resistant states such as obesity can result in an increase in the function and mass of pancreatic β-cells, so that insulin secretion is up-regulated and Type II diabetes does not develop. However, expansion of β-cell mass is not indefinite and may well decrease with time. Changes in circulating concentrations of nutritional factors, such as fatty acids and/or glucose, may lead to a reduction in β-cell mass in vivo. Few previous studies have attempted to explore the interplay between glucose, amino acids and fatty acids with respect to β-cell mass and functional integrity. In the present study, we demonstrate that culture of clonal BRIN-BD11 cells for 24 h with the polyunsaturated fatty acid arachidonic acid (AA) increased β-cell proliferation and enhanced alanine-stimulated insulin secretion. These effects of AA were associated with significant decreases in the cellular consumption of D-glucose and L-alanine as well as decreased rates of production of nitric oxide and ammonia. Conversely 24 h exposure to the saturated fatty acid palmitic acid (PA) was found to decrease β-cell viability (by increasing apoptosis), increase the intracellular concentration of triacylglycerol (triglyceride), while inhibiting alanine-stimulated insulin secretion. These effects of PA were associated with significant increases in D-glucose and L-glutamine consumption as well as nitric oxide and ammonia production. However, L-alanine consumption was decreased in the presence of PA. The effects of AA, but not PA, were additionally dependent on glucose concentration. These studies indicate that AA may have a critical role in maintaining the appropriate mass and function of islet β-cells by influencing rates of cell proliferation and insulin secretion. This regulatory effect may be compromised by high circulating levels of glucose and/or PA, both of which are elevated in Type II diabetes and may impact upon dysfunctional and apoptotic intracellular events in the β-cell.

scholarly journals αB-crystallin/sHSP protects cytochrome c and mitochondrial function against oxidative stress in lens and retinal cells

2012 ◽  
Vol 1820 (7) ◽  
pp. 921-930 ◽  
Author(s):  
Rebecca S. McGreal ◽  
Wanda Lee Kantorow ◽  
Daniel C. Chauss ◽  
Jianning Wei ◽  
Lisa A. Brennan ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Cytochrome C ◽  
Mitochondrial Function ◽  
Retinal Cells ◽  
Αb Crystallin

scholarly journals L-Arginine Reduces Nitro-Oxidative Stress in Cultured Cells with Mitochondrial Deficiency

Nutrients ◽  
2021 ◽  
Vol 13 (2) ◽  
pp. 534
Author(s):  
Camila D. S. Barros ◽  
Jomênica B. Livramento ◽  
Margaret G. Mouro ◽  
Elisa Mieko Suemitsu Higa ◽  
Carlos T. Moraes ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Nitric Oxide ◽  
Mitochondrial Function ◽  
Cultured Cells ◽  
Therapeutic Option ◽  
Protein Nitration ◽  
Mtdna Mutation ◽  
Mitochondrial Mass ◽  
G Cells ◽  
Main Effect

L-Arginine (L-ARG) supplementation has been suggested as a therapeutic option in several diseases, including Mitochondrial Encephalomyopathy, Lactic Acidosis, and Stroke-like syndrome (MELAS), arguably the most common mitochondrial disease. It is suggested that L-ARG, a nitric oxide (NO) precursor, can restore NO levels in blood vessels, improving cerebral blood flow. However, NO also participates in mitochondrial processes, such as mitochondrial biogenesis, the regulation of the respiratory chain, and oxidative stress. This study investigated the effects of L-ARG on mitochondrial function, nitric oxide synthesis, and nitro-oxidative stress in cell lines harboring the MELAS mitochondrial DNA (mtDNA) mutation (m.3243A>G). We evaluated mitochondrial enzyme activity, mitochondrial mass, NO concentration, and nitro-oxidative stress. Our results showed that m.3243A>G cells had increased NO levels and protein nitration at basal conditions. Treatment with L-ARG did not affect the mitochondrial function and mass but reduced the intracellular NO concentration and nitrated proteins in m.3243A>G cells. The same treatment led to opposite effects in control cells. In conclusion, we showed that the main effect of L-ARG was on protein nitration. Lowering protein nitration is probably involved in the mechanism related to L-ARG supplementation benefits in MELAS patients.

Effects of endurance training on apoptotic susceptibility in striated muscle

2011 ◽  
Vol 110 (6) ◽  
pp. 1638-1645 ◽  
Author(s):  
Anna Vainshtein ◽  
Lawrence Kazak ◽  
David A. Hood
Keyword(s):  
Oxidative Stress ◽  
Cytochrome C ◽  
Striated Muscle ◽  
Striated Muscles ◽  
Apoptotic Signaling ◽  
Muscle Disuse ◽  
Mitochondrial Fractions ◽  
Cardiac Muscles ◽  
Apoptosis Inducing Factor

An increase in the production of reactive oxygen species occurs with muscle disuse, ischemic cardiomyopathy, and conditions that arise with senescence. The resulting oxidative stress is associated with apoptosis-related myopathies. Recent research has suggested that chronic exercise is protective against mitochondrially mediated programmed cell death. To further investigate this, we compared soleus (Sol) and cardiac muscles of voluntary wheel-trained (T; 10 wk) and untrained (C) animals. Training produced a 52% increase in muscle cytochrome c oxidase (COX) activity. Sol and left ventricle (LV) strips were isolated and incubated in vitro with H2O2 for 4 h. Strips were then fractionated into cytosolic and mitochondrial fractions. Whole muscle apoptosis-inducing factor (AIF) and Bax/Bcl-2 levels were reduced in both the Sol and LV from T animals. H2O2 treatment induced increases in JNK phosphorylation, cofilin-2 localization to the mitochondria, as well as cytosolic AIF in both Sol and LV of T and C animals, respectively. Mitochondrial Bax and cytosolic cytochrome c were augmented under oxidative stress in the LV only. The H2O2-induced increases in P-JNK, mitochondrial Bax, and cytosolic AIF were ablated in the LV of T animals. These data suggest that short-term oxidative stress can induce apoptotic signaling in striated muscles in vitro. In addition, training can attenuate oxidative stress-induced apoptotic signaling in a tissue-specific manner, with an effect that is most prominent in cardiac muscle.

scholarly journals High-Fish Oil and High-Lard Diets Differently Affect Testicular Antioxidant Defense and Mitochondrial Fusion/Fission Balance in Male Wistar Rats: Potential Protective Effect of ω3 Polyunsaturated Fatty Acids Targeting Mitochondria Dynamics

2019 ◽  
Vol 20 (12) ◽  
pp. 3110 ◽  
Author(s):  
Migliaccio ◽  
Sica ◽  
Di Gregorio ◽  
Putti ◽  
Lionetti
Keyword(s):  
Oxidative Stress ◽  
Fatty Acids ◽  
Fish Oil ◽  
Mitochondrial Function ◽  
Mitochondrial Fusion ◽  
Antioxidant Defenses ◽  
High Fat ◽  
High Fat Diets ◽  
Mitochondria Dynamics ◽  
Fat Diets

High-fat diets rich in fish oil (HFO diet, mainly ω3-PUFAs), in contrast to high-fat diets rich in lard (HL diet, mainly saturated fatty acids) have been shown to induce improvement in mitochondrial function and fusion processes associated with a reduction in reactive oxygen species production in both liver and skeletal muscle. High-fat diets may also impair testicular function, and mitochondria represent important cellular organelles with a pivotal role in reproductive function. Mitochondria are dynamic organelles that frequently undergo fission/fusion processes. A shift toward mitochondrial fusion process has been associated with improvement of mitochondrial function, as well as with ω3-PUFAs protective effects. The present study aimed to analyze the effect of chronic overfeeding (six weeks) with HFO or HL diet on testicular tissue histology, oxidative stress, antioxidant defenses, and mitochondrial fusion (mitofusin 2) and fission (dynamic related protein 1) protein. Our results showed that HFO diet induced less testicular histology impairment, oxidative stress, and apoptosis compared to a HL diet. This finding was associated with an increase in antioxidant activities and a shift toward mitochondrial fusion processes induced by HFO diet compared to HL diet, suggesting that ω3-PUFAs may act as bioactive compound targeting mitochondria dynamics to prevent testicular impairment.

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