Reactive oxygen species, mitochondria, apoptosis and aging

Papa, Sergio; Skulachev, Vladimir P.

doi:10.1007/978-1-4615-6111-8_47

Cited by 220 publications

(175 citation statements)

References 135 publications

Supporting

Mentioning

169

Contrasting

Unclassified

Order By: Relevance

“…The degree of intracellular ROS accumulation and caspase-3 activity was paralleled by the progress of apoptosis. Information regarding the biological significance of ROS has increased considerably in recent years, revealing diverse functions (22,23). Exposure of cells to ROS in a variety of experimental systems leads to apoptosis and to cell damage (23).…”

Section: Discussionmentioning

confidence: 99%

“…Information regarding the biological significance of ROS has increased considerably in recent years, revealing diverse functions (22,23). Exposure of cells to ROS in a variety of experimental systems leads to apoptosis and to cell damage (23). Moreover, targeted disruption of inducible nitric oxide synthase (iNOS) protects against insulin resistance in muscle, indicating the involvement of iNOS in the development of muscle insulin resistance (24).…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Insulin can block apoptosis by decreasing oxidative stress via phosphatidylinositol 3-kinase- and extracellular signal-regulated protein kinase-dependent signaling pathways in HepG2 cells

Kang¹,

Song²,

Kang³

et al. 2003

European Journal of Endocrinology

View full text Add to dashboard Cite

Objective: Insulin has well-known activities in controlling energy metabolism, cellular proliferation and biosynthesis of functional molecules to maintain a biological homeostasis. Recently, several studies have suggested that insulin may protect cells from apoptosis in different cell lines; however, little is known about the nature of its anti-apoptotic activity. In many clinical disorders, including type 2 diabetes mellitus, oxidative stress and the production of reactive oxygen species (ROS) is increased. With these facts as a background, we examined here whether insulin protects HepG2 cells from apoptosis by decreasing oxidative stress and, if so, which signaling steps are involved in this process. Methods: Intracellular DNA content, the degree of nuclear condensation or poly(ADP-ribose) polymerase hydrolysis was measured to verify the occurrence of apoptotic events. Caspase-3 activity and ROS accumulation within cells were also measured. Western blot analysis was performed to identify signaling molecules activated in response to insulin. Results: Serum starvation resulted in a marked accumulation of ROS, activation of caspase-3, and subsequent apoptotic cell death which were, in turn, markedly blocked by the addition of insulin. The anti-apoptotic activity of insulin was sensitive to blockade of two different signaling steps, activations of phosphatidylinositol 3-kinase (PI3 kinase) and extracellular signal-regulated protein kinase (ERK). Conclusion: Insulin exerts an anti-apoptotic activity by suppressing the excessive accumulation of ROS within cells through signaling pathways including stimulation of PI3 kinase and ERK in HepG2 cells.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Insulin can block apoptosis by decreasing oxidative stress via phosphatidylinositol 3-kinase- and extracellular signal-regulated protein kinase-dependent signaling pathways in HepG2 cells

Kang¹,

Song²,

Kang³

et al. 2003

European Journal of Endocrinology

View full text Add to dashboard Cite

show abstract

“…The present data on proton leak are much more consistent with an increasingly advocated role for proton leak in the control of mitochondrial ROS. These are mainly produced during the resting state of the respiratory chain, when the proton gradient (⌬ H ϩ ) is elevated (27), thereby leading to an increased probability for electrons to react directly with dioxygen and to form superoxide and related ROS (28). Because ROS production is low when ⌬ H ϩ is reduced, it has been hypothesized that a mild uncoupling of oxidative phosphorylation during state 4 respiration, by dissipating the proton gradient, would prevent ROS accumulation within the mitochondria (29).…”

Section: Skeletal Muscle Mitochondria and Catch-up Fatmentioning

confidence: 99%

Altered Skeletal Muscle Subsarcolemmal Mitochondrial Compartment During Catch-Up Fat After Caloric Restriction

et al. 2006

View full text Add to dashboard Cite

An accelerated rate of fat recovery (catch-up fat) and insulin resistance are characteristic features of weight recovery after caloric restriction, with implications for the pathophysiology of catch-up growth and weight fluctuations. Using a previously described rat model of weight recovery in which catch-up fat and skeletal muscle insulin resistance have been linked to suppressed thermogenesis per se, we investigated alterations in mitochondrial energetics and oxidative stress in subsarcolemmal (SS) and intermyofibrillar (IMF) skeletal muscle mitochondria. After 2 weeks of semistarvation followed by 1 week of refeeding, the refed rats show persistent and selective reductions in SS mitochondrial mass (assessed from citrate synthase activity in tissue homogenate and isolated mitochondria) and oxidative capacity. Furthermore, the refed rats show, in both SS and IMF muscle mitochondria, a lower aconitase activity (whose inactivation is an index of increased reactive oxygen species [ROS]), associated with higher superoxide dismutase activity and increased proton leak. Taken together, these studies suggest that diminished skeletal muscle mitochondrial mass and function, specifically in the SS mitochondrial compartment, contribute to the high metabolic efficiency for catch-up fat after caloric restriction and underscore a potential link between diminished skeletal muscle SS mitochondrial energetics, increased ROS concentration, and insulin resistance during catch-up fat. Diabetes

show abstract

“…9,11 Superoxide production is enhanced if the rate of electron transport is limited by hyperpolarization of the inner mitochondrial membrane subsequent to the buildup of a large proton gradient that occurs with overwhelming fuel supply or with the functional impairment of one or more electron transport complexes. 9,10,12,13 Uncoupling protein-2 (UCP2), a recently identified inner mitochondrial membrane anion carrier, 14,15 has emerged as a sensor 16,17 and potentially critical negative regulator of mitochondrial superoxide production. 18,19 UCP2 is able to mediate proton leaks in mammalian cells 20 and keep the membrane potential sufficiently low to minimize superoxide production.…”

mentioning

confidence: 99%

Uncoupling protein-2 deficiency promotes oxidant stress and delays liver regeneration in mice

et al. 2004

View full text Add to dashboard Cite

The control of liver regeneration remains elusive. Because reactive oxygen species (ROS) are able to mediate cell growth arrest and activate proteins that inhibit the cell cycle, ROS production may have a negative impact on liver regeneration. We examined how liver regeneration is affected by uncoupling protein-2 (UCP2), an inner mitochondrial membrane carrier that senses and negatively regulates superoxide production. Liver regeneration was monitored up to 5 days and was found to be significantly delayed in UCP2 ؊/؊ mice after partial hepatectomy. Apoptosis rates in UCP2 ؉/؉ and UCP2 ؊ /؊ liver remnants were similar, while parameters of cell proliferation indicated a diminished response in UCP2 ؊ /؊ mice with corresponding changes in the expression of key cell cycle regulatory proteins and prolonged activation of stress-responsive protein kinase p38. Levels of malondialdehyde, a marker of ROS generation and oxidant stress, were elevated in UCP2 ؊ /؊ livers at every examined time point. Liver remnants of UCP2 ؉ /؉ mice 48 hours post-hepatectomy showed a fourfold increase in the expression of UCP2 protein primarily detected in hepatocytes. In conclusion, our results suggest that absent or insufficient UCP2 function in the regenerating liver results in increased ROS production and negatively modulates the control of cell cycle.

show abstract

Reactive oxygen species, mitochondria, apoptosis and aging

Cited by 220 publications

References 135 publications

Insulin can block apoptosis by decreasing oxidative stress via phosphatidylinositol 3-kinase- and extracellular signal-regulated protein kinase-dependent signaling pathways in HepG2 cells

Insulin can block apoptosis by decreasing oxidative stress via phosphatidylinositol 3-kinase- and extracellular signal-regulated protein kinase-dependent signaling pathways in HepG2 cells

Altered Skeletal Muscle Subsarcolemmal Mitochondrial Compartment During Catch-Up Fat After Caloric Restriction

Uncoupling protein-2 deficiency promotes oxidant stress and delays liver regeneration in mice

Contact Info

Product

Resources

About