The effect of nitric oxide on mitochondrial respiration.

This article reviews the interactions between nitric oxide (NO) and mitochondrial respiration. Mitochondrial ATP synthesis is responsible for virtually all energy production in mammals, and every other process in living organisms ultimately depends on that energy production. Furthermore, both necrosis and apoptosis, that summarize the main forms of cell death, are intimately linked to mitochondrial integrity.

Subcellular distribution of ERK phosphorylation in tyrosine and threonine depends on redox status in murine lung cells.

Activation of ERK1/2 implies the phosphorylation of tyrosine (pTyr) and threonine (pThr) by MEK1/2; both reactions were thought to be cytoplasmic, promoting ERK to reach the nucleus where it activates several transcription factors. In addition, H2O2 concentrations are known to modulate ERK intracellular translocation, which impacts on cellular proliferation. In this context, the objective of this work was to study the sequence of ERK phosphorylation under two redox conditions and to analyze a putative mitochondrial contribution to this process, in LP07 murine lung cells.

Characterization of Tunneling Nanotubes in Wharton's jelly Mesenchymal Stem Cells. An Intercellular Exchange of Components between Neighboring Cells.

Intercellular communication is one of the most important events in cell population behavior. In the last decade, tunneling nanotubes (TNTs) have been recognized as a new form of long distance intercellular connection. TNT function is to allow molecular and subcellular structure exchange between neighboring cells via the transfer of molecules and organelles such as calcium ions, prions, viral and bacterial pathogens, small lysosomes and mitochondria.

Cardiac-specific overexpression of thioredoxin 1 attenuates mitochondrial and myocardial dysfunction in septic mice.

Sepsis-induced myocardial dysfunction is associated with increased oxidative stress and mitochondrial dysfunction. Current evidence suggests a protective role of thioredoxin-1 (Trx1) in the pathogenesis of cardiovascular diseases. However, it is unknown yet a putative role of Trx1 in sepsis-induced myocardial dysfunction, in which oxidative stress is an underlying cause.

SPARC gene deletion protects against toxic liver injury and is associated to an enhanced proliferative capacity and reduced oxidative stress response.

SPARC, also known as osteonectin and BM-40, is a matricellular protein with a number of biological functions. Hepatic SPARC expression is induced in response to thioacetamide, bile-duct ligation, and acute injuries such as concanavalin A and lipopolysacharide (LPS)/D-galactosamine. We have previously demonstrated that the therapeutic inhibition of SPARC or SPARC gene deletion protected mice against liver injury.

Role of thioredoxin-1 in ischemic preconditioning, postconditioning and aged ischemic hearts.

Thioredoxin is one of the most important cellular antioxidant systems known to date, and is responsible of maintaining the reduced state of the intracellular space. Trx-1 is a small cytosolic protein whose transcription is induced by stress. Therefore it is possible that this antioxidant plays a protective role against the oxidative stress caused by an increase of reactive oxygen species concentration, as occurs during the reperfusion after an ischemic episode.

Loss of myocardial protection against myocardial infarction in middle-aged transgenic mice overexpressing cardiac thioredoxin-1.

Thioredoxin-1 (Trx1) protects the heart from ischemia/reperfusion (I/R) injury. Given that the age at which the first episode of coronary disease takes place has considerably decreased, life at middle-aged (MA) emerges as a new field of study. The aim was determine whether infarct size, Trx1 expression and activity, Akt and GSK-3β were altered in young (Y) and MA mice overexpressing cardiac Trx1, and in a dominant negative (DN-Trx1) mutant of Trx1.

The pan-caspase inhibitor Emricasan (IDN-6556) decreases liver injury and fibrosis in a murine model of non-alcoholic steatohepatitis.

Background & Aims: Hepatocyte apoptosis, the hallmark of non-alcoholic steatohepatitis (NASH) contributes to liver injury and fibrosis. Although, both the intrinsic and extrinsic apoptotic pathways are involved in the pathogenesis of NASH, the final common step of apoptosis is executed by a family of cysteine-proteases termed caspases. Thus, our aim was to ascertain if administration of Emricasan, a pan-caspase inhibitor, ameliorates liver injury and fibrosis in a murine model of NASH.

The LRRK2 G2019S mutation in a series of Argentinean patients with Parkinson's disease: clinical and demographic characteristics.

Objectives: To determine clinical characteristics and frequency of leucine-rich repeat kinase 2 gene (LRRK2) mutations in a cohort of patients with Parkinson's disease (PD) from Argentina.

Background: Variation in the LRRK2 gene represents the most common genetic determinant of PD, only few data are available from Latin-America.

Design/methods: Informed consent was obtained and all studies were approved by the Institutional Review Boards.

Progesterone prevents mitochondrial dysfunction in the spinal cord of wobbler mice.

In the Wobbler mouse, a mutation of the Vps54 protein increases oxidative stress in spinal motoneurons, associated to toxic levels of nitric oxide and hyperactivity of nitric oxide synthase (NOS). Progesterone neuroprotection has been reported for several CNS diseases, including the Wobbler mouse neurodegeneration. In the present study, we analyzed progesterone effects on mitochondrial-associated parameters of symptomatic Wobbler mice.

Diastolic function during hemorrhagic shock in rabbits.

Hemorrhage (H) is associated with a left ventricular (LV) dysfunction. However, the diastolic function has not been studied in detail. The main goal was to assess the diastolic function both during and 120 min after bleeding, in the absence and in the presence of L-NAME.

New algorithm to determine true colocalization in combination with image restoration and time-lapse confocal microscopy to MAP kinases in mitochondria.

The subcellular localization and physiological functions of biomolecules are closely related and thus it is crucial to precisely determine the distribution of different molecules inside the intracellular structures. This is frequently accomplished by fluorescence microscopy with well-characterized markers and posterior evaluation of the signal colocalization. Rigorous study of colocalization requires statistical analysis of the data, albeit yet no single technique has been established as a standard method.

Defective leptin-AMP-dependent kinase pathway induces nitric oxide release and contributes to mitochondrial dysfunction and obesity in ob/ob mice.

Aims: Obesity arises on defective neuroendocrine pathways that increase energy intake and reduce mitochondrial metabolism. In the metabolic syndrome, mitochondrial dysfunction accomplishes defects in fatty acid oxidation and reciprocal increase in triglyceride content with insulin resistance and hyperglycemia. Mitochondrial inhibition is attributed to reduced biogenesis, excessive fission, and low adipokine-AMP-activated protein kinase (AMPK) level, but lateness of the respiratory chain contributes to perturbations.

[Nutritional status, systemic inflammatory response syndrome and mortality in the elderly hospitalized patient].

In order to evaluate the relationship between systemic inflammatory response and mortality in the older hospitalized patient, we developed a prospective cohort study in which we evaluated a nutritional score (SGA), years of instruction, functional status, organic failure (Marshall), presence of sepsis, comorbidities (Charlson), cognitive state (MMSE), albumin, erythrocyte sedimentation rate and mortality. Fifty two patients were included, 19 men (36.5%) and 33 women (63.

A new paradigm for MAPK: structural interactions of hERK1 with mitochondria in HeLa cells.

Extracellular signal-regulated protein kinase 1 and 2 (ERK1/2) are members of the MAPK family and participate in the transduction of stimuli in cellular responses. Their long-term actions are accomplished by promoting the expression of specific genes whereas faster responses are achieved by direct phosphorylation of downstream effectors located throughout the cell. In this study we determined that hERK1 translocates to the mitochondria of HeLa cells upon a proliferative stimulus.

Akt1 intramitochondrial cycling is a crucial step in the redox modulation of cell cycle progression.

Akt is a serine/threonine kinase involved in cell proliferation, apoptosis, and glucose metabolism. Akt is differentially activated by growth factors and oxidative stress by sequential phosphorylation of Ser(473) by mTORC2 and Thr(308) by PDK1. On these bases, we investigated the mechanistic connection of H(2)O(2) yield, mitochondrial activation of Akt1 and cell cycle progression in NIH/3T3 cell line with confocal microscopy, in vivo imaging, and directed mutagenesis.

[Tolerance and autoimmunity. Novel therapeutic approaches].

The main function of the immune system is to protect the individual against potentially dangerous pathogens. It comprises innate and adaptive cellular and soluble components, both with the capacity to discriminate between harmful and harmless. These processes are regulated by homeostatic mechanisms that constitute the so-called immunological tolerance, which aims to limit the prolonged action of immune mediators and to silence the generation of potentially autoaggressive components.

Mitochondrial nitric oxide synthase: a masterpiece of metabolic adaptation, cell growth, transformation, and death.

Mitochondria are specialized organelles that control energy metabolism and also activate a multiplicity of pathways that modulate cell proliferation and mitochondrial biogenesis or, conversely, promote cell arrest and programmed cell death by a limited number of oxidative or nitrative reactions. Nitric oxide (NO) regulates oxygen uptake by reversible inhibition of cytochrome oxidase and the production of superoxide anion from the mitochondrial electron transfer chain. In this sense, NO produced by mtNOS will set the oxygen uptake level and contribute to oxidation-reduction reaction (redox)-dependent cell signaling.

Detection of a mitochondrial kinase complex that mediates PKA-MEK-ERK-dependent phosphorylation of mitochondrial proteins involved in the regulation of steroid biosynthesis.

In order to achieve the goal of this article, as an example we will describe the strategies followed to analyze the presence of the multi-kinase complex at the mitochondria and the posttranslational modification of two key mitochondrial proteins, which participate in the regulation of cholesterol transport across the mitochondrial membranes and in the regulation of steroid biosynthesis. Hormones, ions or growth factors modulate steroid biosynthesis by the posttranslational phosphorylation of proteins. The question still remains on how phosphorylation events transmit a specific signal to its mitochondrial site of action.

The formation of peroxynitrite in the applied physiology of mitochondrial nitric oxide.

Mitochondria require nitric oxide ((.)NO) to exert a delicate control of metabolic rate as well as to regulate life functions, cell cycle activation and arrest, and apoptosis. All activities depend on the matrical (.

Tumor cell phenotype is sustained by selective MAPK oxidation in mitochondria.

Mitochondria are major cellular sources of hydrogen peroxide (H(2)O(2)), the production of which is modulated by oxygen availability and the mitochondrial energy state. An increase of steady-state cell H(2)O(2) concentration is able to control the transition from proliferating to quiescent phenotypes and to signal the end of proliferation; in tumor cells thereby, low H(2)O(2) due to defective mitochondrial metabolism can contribute to sustain proliferation. Mitogen-activated protein kinases (MAPKs) orchestrate signal transduction and recent data indicate that are present in mitochondria and regulated by the redox state.