Increased oxidative stress and mitochondrial impairments associated with increased expression of TNF-α and caspase-3 in palmitic acid-induced lipotoxicity in myoblasts.

Saturated fatty acids, whose circulating levels are markedly increased in the body, significantly affect the growth and functions of skeletal muscle. These fatty acids may exert a detrimental effect on the undifferentiated skeletal myoblasts that may adversely affect their differentiation. In the present study, the exposure of myoblasts to excess palmitic acid caused an elevation of tumor necrosis factor-α expression and an increase in reactive oxygen species levels consistent with the enhanced inflammation and oxidative stress.

Cognitive impairments in type 2 diabetes, risk factors and preventive strategies.

Mild cognitive impairment (MCI) is a modifiable risk factor in progression of several diseases including dementia and type 2 diabetes. If cognitive impairments are not reversed at an early stage of appearance of symptoms, then the prolonged pathogenesis can lead to dementia and Alzheimer's disease (AD). Therefore, it is necessary to detect the risk factors and mechanism of prevention of cognitive dysfunction at an early stage of disease.

Downregulation of sirtuin 3 by palmitic acid increases the oxidative stress, impairment of mitochondrial function, and apoptosis in liver cells.

Elevated levels of saturated fatty acids show a strong cytotoxic effect in liver cells. Sirtuin 3 (SIRT3), a mitochondrially localized member of NAD -dependent deacetylase has been shown to protect hepatocytes against the oxidative stress. The role of SIRT3 on the cytotoxicity caused by fatty acids in liver cells is not fully understood.

Metabolic enzymes dysregulation in heart failure: the prospective therapy.

The heart failure accounts for the highest mortality rate all over the world. The development of preventive therapeutic approaches is still in their infancy. Owing to the extremely high energy demand of the heart, the bioenergetics pathways need to respond efficiently based on substrate availability.

Study of apoptosis-related interactions in colorectal cancer.

Abnormalities in apoptotic functions contribute to the pathogenesis of colorectal cancer. In this study, molecular interactions behind the apoptotic regulation have been explored. For this purpose, enrichment analysis was performed considering microRNAs (miRNAs) that putatively target TP53 and altered during colon cancer.

Neurodegenerative diseases: From available treatments to prospective herbal therapy.

Neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease and many others represent a relevant health problem with age worldwide. Efforts have been made in recent years to discover the mechanism of neurodegenerative diseases and prospective therapy that can help to slow down the effects of the aging and prevent these diseases. Since pathogenesis of these diseases involves multiple factors therefore the important task for neuroscientists is to identify such multiple factors and prevent age-associated neurodegenerative diseases.

Flavonoid-based therapies in the early management of neurodegenerative diseases.

During the past several years, there has been enormous progress in the understanding of the causative factors that initiate neuronal damage in various neurodegenerative diseases, including Alzheimer disease, Parkinson disease, multiple sclerosis, amyotrophic lateral sclerosis, and Huntington disease. Preventing neuronal damage and neuronal death will have a huge clinical benefit. However, despite major advances in causative factors that trigger these neurodegenerative diseases, to date there have been no therapies available that benefit patients who suffer from these diseases.

Mitochondrial sirtuins: emerging roles in metabolic regulations, energy homeostasis and diseases.

The energy production and metabolic homeostasis are well-orchestrated networks of carbohydrate, lipid and protein metabolism. These metabolic pathways are integrated by a key cytoplasmic organelle, the mitochondria, leading to production of many metabolic intermediates and harvest cellular energy in the form of ATP. Sirtuins are a highly conserved family of proteins that mediate cellular physiology and energy demands in response to metabolic inputs.

Flavonoids in modulation of cell survival signalling pathways.

Flavonoids, a family of polyphenols, generally found in various fruits and vegetables, as well as in many plant beverages such as tea, pomegranate juice, raspberry, blueberries, and red wine. Recently, studies on flavonoids have attracted scientific attention as a potential nutritional strategy to prevent a broad range of chronic disorders. Many studies suggest that consumption of these flavonoids in sufficient amount plays neuroprotective, cardioprotective, anti-inflammatory, and chemopreventive roles.

Amyloid-β as a modulator of synaptic plasticity.

Alzheimer's disease is associated with synapse loss, memory dysfunction, and pathological accumulation of amyloid-β (Aβ) in plaques. However, an exclusively pathological role for Aβ is being challenged by new evidence for an essential function of Aβ at the synapse. Aβ protein exists in different assembly states in the central nervous system and plays distinct roles ranging from synapse and memory formation to memory loss and neuronal cell death.

Importance of cytochrome c redox state for ceramide-induced apoptosis of human mammary adenocarcinoma cells.

Background: Ceramides are intracellular lipid mediator implicated in various cellular responses, including oxidative stress and programmed cell death. Studies demonstrated strong links between ceramide and the mitochondria in the regulation of apoptosis. However, the mechanism of apoptosis induced by ceramides is not fully understood.

Alpha-synuclein overexpression and aggregation exacerbates impairment of mitochondrial functions by augmenting oxidative stress in human neuroblastoma cells.

Overexpression of alpha-synuclein and oxidative stress has been implicated in the neuronal cell death in Parkinson's disease. Alpha-synuclein associates with mitochondria and excessive accumulation of alpha-synuclein causes impairment of mitochondrial functions. However, the mechanism of mitochondrial impairment caused by alpha-synuclein is not fully understood.

mAtNOS1 induces apoptosis of human mammary adenocarcinoma cells.

mAtNOS1 is a novel gene recently reported in mammalian genome with functions that are not fully understood. The present study shows that in human mammary adenocarcinoma MCF-7 cells, mAtNOS1 expression increases mitochondrial nitric oxide and calcium. Our study further shows that overexpression of mAtNOS1 induces apoptosis in MCF-7 cells by increasing mitochondrial protein tyrosine nitration and cytochrome c release.

Age-related decreases in NAD(P)H and glutathione cause redox declines before ATP loss during glutamate treatment of hippocampal neurons.

Age-related glutamate excitotoxicity depends in an unknown manner on active mitochondria, which are key determinants of the cellular redox potential. Compared with embryonic and middle-aged neurons, old-aged rat hippocampal neurons have a lower resting reduced nicotinamide adenine dinucleotide (phosphate) (NAD(P)H) and a lower redox ratio (NAD(P)H/flavin adenine nucleotide). Glutamate treatment resulted in an initial increase in NAD(P)H concentrations in all ages, followed by a profound calcium-dependent, age-related decline in NAD(P)H concentration and redox ratio.

Detection assays for determination of mitochondrial nitric oxide synthase activity; advantages and limitations.

Nitric oxide (NO) is a reactive radical synthesized by members of the NO synthase (NOS) family, including mitochondrial-specific NOS (mtNOS). Some of the assays used for the determination of cytoplasmic NOS activity have been utilized to detect mtNOS activity. However, it seems that many of those assays need to be adjusted and optimized to detect NO in the unique environment of mitochondria.

mAtNOS1 regulates mitochondrial functions and apoptosis of human neuroblastoma cells.

mAtNOS1 is a novel gene recently reported in mammalian cells with functions that are not fully understood. The present study generated human neuroblastoma SHSY cells over- and underexpressing mAtNOS1 and shows that mAtNOS1 is involved in regulating mitochondrial nitric oxide, mitochondrial transmembrane potential, protein tyrosine nitration, cytochrome c release, and apoptosis of those cells.

Significance of mitochondrial calcium and nitric oxide for apoptosis of human breast cancer cells induced by tamoxifen and etoposide.

In the present study, we tested the significance of mitochondria for apoptosis upon exposure to tamoxifen and etoposide using two human breast cancer cell lines, MCF-7 and MDA-MB-231. We showed that both tamoxifen and etoposide induced apoptosis, increased intramitochondrial calcium and nitric oxide, and decreased mitochondrial transmembrane potential in both cell lines. Both drugs increased mitochondrial protein tyrosine nitration and caused release of cytochrome c from the mitochondria of both cell lines.

Inactivation of mitochondrial respiratory chain complex I leads mitochondrial nitric oxide synthase to become pro-oxidative.

We recently demonstrated that mitochondrial nitric oxide synthase (mtNOS) functionally couples with mitochondrial respiratory chain complex I to produce nitric oxide [M.S. Parihar, R.

Association of mitochondrial nitric oxide synthase activity with respiratory chain complex I.

The present study shows that rat liver and brain mitochondrial nitric oxide synthase (mtNOS) are functionally associated with mitochondrial respiratory chain complex I. When complex I is activated, mtNOS exerts high activity and generates nitric oxide, whereas inactivation of complex I leads mtNOS to abandon its NOS activity. Functional association of mtNOS with complex I is potentially important in regulating mtNOS activity and mitochondrial functions.

Mitochondria in multiple sclerosis.

Multiple sclerosis (MS) is a neurological disorder of the central nervous system characterized by demyelination and neurodegeneration. Although the pathogenesis of MS is not completely understood, various studies suggest that immune-mediated loss of myelin and mitochondrial dysfunction are associated with the disease. Mitochondria are one of the main cellular sources of reactive oxygen species (ROS) and reactive nitrogen species (RNS) and play a pivotal role in many neuro-pathological conditions.

12(S)-hydroperoxyeicosatetraenoic acid (12-HETE) increases mitochondrial nitric oxide by increasing intramitochondrial calcium.

12(S)-hydroxyeicosatetraenoic acid (12-HETE) is one of the metabolites of arachidonic acid involved in pathological conditions associated with mitochondria and oxidative stress. The present study tested effects of 12-HETE on mitochondrial functions. In isolated rat heart mitochondria, 12-HETE increases intramitochondrial ionized calcium concentration that stimulates mitochondrial nitric oxide (NO) synthase (mtNOS) activity.

Oxidative stress and anti-oxidative mobilization in burn injury.

A severe burn is associated with release of inflammatory mediators which ultimately cause local and distant pathophysiological effects. Mediators including Reactive Oxygen Species (ROS) and Reactive Nitrogen Species (RNS) are increased in affected tissue, which are implicated in pathophysiological events observed in burn patients. The purpose of this article is to understand the role of oxidative stress in burns, in order to develop therapeutic strategies.

Hypoxia/reoxygenation of isolated rat heart mitochondria causes cytochrome c release and oxidative stress; evidence for involvement of mitochondrial nitric oxide synthase.

The objective of the present study was to delineate the molecular mechanisms for mitochondrial contribution to oxidative stress induced by hypoxia and reoxygenation in the heart. The present study introduces a novel model allowing real-time study of mitochondria under hypoxia and reoxygenation, and describes the significance of intramitochondrial calcium homeostasis and mitochondrial nitric oxide synthase (mtNOS) for oxidative stress. The present study shows that incubating isolated rat heart mitochondria under hypoxia followed by reoxygenation, but not hypoxia per se, causes cytochrome c release from the mitochondria, oxidative modification of mitochondrial lipids and proteins, and inactivation of mitochondrial enzymes susceptible to inactivation by peroxynitrite.

Simultaneous age-related depolarization of mitochondrial membrane potential and increased mitochondrial reactive oxygen species production correlate with age-related glutamate excitotoxicity in rat hippocampal neurons.

Mitochondria are implicated in glutamate excitotoxicity by causing bioenergetic collapse, loss of Ca(2+) homeostasis, and generation of reactive oxygen species (ROS), all of which become increasingly important clinically with age. Little is known about how aging affects the relative importance of mitochondrial membrane potential (DeltaPsi(m)) and ROS production. To determine aging affects on DeltaPsi(m) and ROS production in individual somal and axonal/dendritic mitochondria, we compared ROS production while simultaneously monitoring DeltaPsi(m) before and after glutamate treatment of live neurons from embryonic (day 18), middle-aged (9-12 months), and old (24 months) rats.

Mitoenergetic failure in Alzheimer disease.

Brain cells are highly energy dependent for maintaining ion homeostasis during high metabolic activity. During active periods, full mitochondrial function is essential to generate ATP from electrons that originate with the oxidation of NADH. Decreasing brain metabolism is a significant cause of cognitive abnormalities of Alzheimer disease (AD), but it remains uncertain whether this is the cause of further pathology or whether synaptic loss results in a lower energy demand.