Mitochondrial Mechanisms in Immunity and Inflammatory Conditions: Beyond Energy Management.

The growing importance of mitochondria in the immune response and inflammation is multifaceted. Unraveling the different mechanisms by which mitochondria have a relevant role in the inflammatory response beyond the energy management of the process is necessary for improving our understanding of the host immune defense and the pathogenesis of various inflammatory diseases and syndromes. Mitochondria are relevant in the immune response at different levels, including releasing activation molecules, changing its structure and function to accompany the immune response, and serving as a structural base for activating intermediates as NLRP3 inflammasome.

Mitochondrial HO metabolism as central event of heart complex I syndrome in early diabetes.

Hydrogen peroxide is the main metabolite effective in redox regulation and it is considered an insulinomimetic agent, with insulin signalling being essential for normal mitochondrial function in cardiomyocytes. Therefore, the aim of this work was to deeply analyse the heart mitochondrial HO metabolism, in the early stage of type 1 diabetes. Diabetes was induced by Streptozotocin (STZ, single dose, 60 mg × kg, ip.

Oxidative metabolism in the cardiorespiratory system after an acute exposure to nickel-doped nanoparticles in mice.

There is an increasing concern over the harmful effects that metallic nanoparticles (NP) may produce on human health. Due to their redox properties, nickel (Ni) and Ni-containing NP are particularly relevant. Hence, the aim of this study was to establish the toxicological mechanisms in the cardiorespiratory oxidative metabolism initiated by an acute exposure to Ni-doped-NP.

Energy management and mitochondrial dynamics in cerebral cortex during endotoxemia.

Mitochondria play an essential role in inflammatory processes such as sepsis or endotoxemia, contributing to organ-cellular redox metabolism, emerging as the energy hub of the cell, and as an important center of action of second messengers. In this work, we aimed to elucidate the energy state, redox balance, and mitochondrial remodeling status in cerebral cortex in an experimental model of endotoxemia. Female Sprague-Dawley rats were subjected to a single dose of LPS (ip 8 mg kg body weight) for 6 h.

Urban air pollution induces alterations in redox metabolism and mitochondrial dysfunction in mice brain cortex.

Previous reports indicate that the central nervous system (CNS) is a target of air pollution, causing tissue damage and functional alterations. Oxidative stress and neuroinflammation have been pointed out as possible mechanisms mediating these effects. The aim of this work was to study the chronic effects of urban air pollution on mice brain cortex, focusing on oxidative stress markers, and mitochondrial function.

Mitochondrial Dynamics and VMP1-Related Selective Mitophagy in Experimental Acute Pancreatitis.

Mitophagy and zymophagy are selective autophagy pathways early induced in acute pancreatitis that may explain the mild, auto limited, and more frequent clinical presentation of this disease. Adequate mitochondrial bioenergetics is necessary for cellular restoration mechanisms that are triggered during the mild disease. However, mitochondria and zymogen contents are direct targets of damage in acute pancreatitis.

Acute hypobaric hypoxia and cardiac energetic response in prepubertal rats: Role of nitric oxide.

New Findings: What is the central question of this study? In adult rat hearts, exposure to hypobaric hypoxia increases tolerance to hypoxia-reoxygenation, termed endogenous cardioprotection. The mechanism involves the nitric oxide system and modulation of mitochondrial oxygen consumption. What is the cardiac energetic response in prepubertal rats exposed to hypobaric hypoxia? What is the main finding and its importance? Prepubertal rats, unlike adult rats, did not increase tolerance to hypoxia-reoxygenation in response acute exposure to hypobaric hypoxia, which impaired cardiac contractile economy.

Mitochondrial bioenergetics links inflammation and cardiac contractility in endotoxemia.

There is current awareness about the central role of mitochondrial dysfunction in the development of cardiac dysfunction in systemic inflammatory syndromes, especially in sepsis and endotoxemia. The aim of this work was to elucidate the mechanism that governs the link between the severity of the systemic inflammatory insult and mitochondrial function, analysing the consequences on heart function, particularly in cardiac contractile state. Female Sprague-Dawley rats were subjected to low-grade endotoxemia (i.

Alpha-synuclein mitochondrial interaction leads to irreversible translocation and complex I impairment.

α-synuclein is involved in both familial and sporadic Parkinson's disease. Although its interaction with mitochondria has been well documented, several aspects remains unknown or under debate such as the specific sub-mitochondrial localization or the dynamics of the interaction. It has been suggested that α-synuclein could only interact with ER-associated mitochondria.

Cardiac dysfunction, mitochondrial architecture, energy production, and inflammatory pathways: Interrelated aspects in endotoxemia and sepsis.

Septic patients with myocardial dysfunction have a 3-fold increase in mortality compared with patients without cardiovascular impairment, and usually show myocarditis, disruption of the contractile apparatus, increased amounts of interstitial collagen, and damaged mitochondria. The presence of nitric oxide and cytokines in cardiac tissue constitute the molecular markers and the intracellular messengers of inflammatory conditions in the heart due to the onset of sepsis and endotoxemia, derived from the nuclear factor-κB pathway activation and proinflammatory gene transcription. Sepsis occurs with an exacerbated inflammatory response that damages tissue mitochondria and impaired bioenergetic processes.

Selective TNF-α targeting with infliximab attenuates impaired oxygen metabolism and contractile function induced by an acute exposure to air particulate matter.

Inflammation plays a central role in the onset and progression of cardiovascular diseases associated with the exposure to air pollution particulate matter (PM). The aim of this work was to analyze the cardioprotective effect of selective TNF-α targeting with a blocking anti-TNF-α antibody (infliximab) in an in vivo mice model of acute exposure to residual oil fly ash (ROFA). Female Swiss mice received an intraperitoneal injection of infliximab (10 mg/kg body wt) or saline solution, and were intranasally instilled with a ROFA suspension (1 mg/kg body wt).

α-Lipoic acid protects kidney from oxidative stress and mitochondrial dysfunction associated to inflammatory conditions.

An adequate redox status is important for maintaining mitochondrial function in inflammatory conditions. The aim of this work was to evaluate the effects of α-lipoic acid (LA) in kidney oxidative metabolism and mitochondrial function in lipopolysaccharide (LPS) treated rats. Sprague-Dawley rats (female, 45 ± 5 days old) were treated with LPS (10 mg kg(-1)) and/or LA (100 mg kg(-1)).

Cardiac mitochondrial biogenesis in endotoxemia is not accompanied by mitochondrial function recovery.

Mitochondrial biogenesis emerges as a compensatory mechanism involved in the recovery process in endotoxemia and sepsis. The aim of this work was to analyze the time course of the cardiac mitochondrial biogenesis process occurring during endotoxemia, with emphasis on the quantitative analysis of mitochondrial function. Female Sprague-Dawley rats (45 days old) were ip injected with LPS (10 mg/kg).

Reactive oxygen species produced by NADPH oxidase and mitochondrial dysfunction in lung after an acute exposure to residual oil fly ashes.

Reactive O2 species production triggered by particulate matter (PM) exposure is able to initiate oxidative damage mechanisms, which are postulated as responsible for increased morbidity along with the aggravation of respiratory diseases. The aim of this work was to quantitatively analyse the major sources of reactive O2 species involved in lung O2 metabolism after an acute exposure to Residual Oil Fly Ashes (ROFAs). Mice were intranasally instilled with a ROFA suspension (1.

Endotoxemia impairs heart mitochondrial function by decreasing electron transfer, ATP synthesis and ATP content without affecting membrane potential.

Acute endotoxemia (LPS, 10 mg/kg ip, Sprague Dawley rats, 45 days old, 180 g) decreased the O₂ consumption of rat heart (1 mm³ tissue cubes) by 33% (from 4.69 to 3.11 μmol O₂/min.

In situ and real time muscle chemiluminescence determines singlet oxygen involvement in oxidative damage during endotoxemia.

Many studies have reported the occurrence of oxidative stress in different models of sepsis, but no measurements in real time and in non-invasive manner in an acute model of endotoxemia were done, being its mechanism still under debate. In the present work, we have used in situ surface chemiluminescence to evaluate the reactive oxygen species steady-state concentrations and to identify the main chemical species involved in this phenomenon. Experimental endotoxemia provoked a twofold increase in skeletal muscle chemiluminescence (control value: 31+/-4cps/cm(2)).

The oxidative stress and the mitochondrial dysfunction caused by endotoxemia are prevented by alpha-lipoic acid.

The aims of this work were to study the mitochondrial function and to evaluate (a) the oxidative stress in real time in an acute model of endotoxemia and (b) the effect of alpha-lipoic acid (LA, 100 mg/kg) as a therapeutic strategy to be considered. In rats treated with lipopolisaccharide (LPS, 10 mg/kg), a 1.4-fold increase was observed in in situ skeletal muscle chemiluminescence.

Study on homocysteine levels and methylenetetrahydrofolate reductase gene variant (C677T) in a population of Buenos Aires City.

Unlabelled: The substitution of cytosine (C) by thymine (T) at nucleotide 677 of the methylenetetrahydrofolate reductase (MTHFR) gene, which converts an alanine to a valine residue, is a frequent polymorphism with reduced specific activity, associated with moderate increase in plasma homocysteine levels (tHcy) and risk of vascular diseases.

Objectives: This study was designed to investigate an association of this polymorphism with tHcy and vascular risk factors.

Methods: We used a cross-sectional study on subjects affiliated to three health centers from Buenos Aires city.