Paola Venditti - Academia.edu (original) (raw)

Papers by Paola Venditti

Journal of Comparative Physiology B-biochemical Systemic and Environmental Physiology, 1996

We investigated the effects on the electrophysiological properties of ventricular muscle fibres f... more We investigated the effects on the electrophysiological properties of ventricular muscle fibres from lizards kept at 20 ~ of mild and severe hyperthyroidism. The hyperthyroidism was induced by a 4day treatment with either 0.025 or 1.0 ~tg triiodothyronine g-1 body weight, documented by increased serum levels of thyroid hormone. Triiodothyronine treatment did not modify the duration of the action potential recorded in vitro at 25 ~ from ventricular muscles stimulated at 1 Hz. Recordings at higher temperatures were associated with a faster repolarization phase and a decrease of action potential duration in both euthyroid and hyperthyroid animals. However, in lizards treated with 1.0gg triiodothyronine 9 g-~ body weight, the 90% repolarization recovery times at 30 and 35 ~ (95.6 _ 14.9 ms and 53.0 _+ 6.0ms, respectively), were significantly shorter than normal (177.6 + 29.2 and 107.2 _+ 18.1 ms, respectively). Action potential duration was also dependent on stimulation frequency of the preparations. Increased frequency led to significant decrease of the duration of action potentials recorded at 25~ In euthyroid preparations the reductions in 90% repolarization recovery time, owing to increases in stimulation frequency to 2.5 and 5Hz, were 19.3 _+ 1.7 and 35.6 _+ 2.0 ms, respectively. In hyperthyroid preparations, the reductions in the 90% recovery time due to stimulus frequency increases varied from 35.4 _+ 1.9 and 58.1 ___ 2.1 ms at low hormone doses to 38.9 _+ 2.0 and 58.2 __ 2.1 ms at high hormone doses. As a result of these differences, the action potential durations recorded from the two hyperthyroid preparations at high stimulation rates were shorter than from euthyroid preparations, The results obtained suggest that lizard cardiac tissue is responsive to hormone action at low

Journal of Bioenergetics and Biomembranes, Dec 14, 2017

We studied the effects of adrenaline administration and depletion (induced by reserpine) on rat l... more We studied the effects of adrenaline administration and depletion (induced by reserpine) on rat liver oxidative metabolism. We showed that adrenaline increases, and reserpine decreases aerobic capacity (inferred by cytochrome oxidase activity) in tissue modifying the hepatic content of mitochondrial proteins without changing mitochondrial aerobic capacity. The changes in tissue cytochrome oxidase activity, which agreed with the expression levels of factors involved in mitochondrial biogenesis, such as PGC-1, NRF-1, and NRF-2, were associated with similar changes in tissue and mitochondrial State 3 respiration. Adrenaline and reserpine induced extensive lipid and protein oxidative damage in tissue and mitochondria. The increase in H 2 O 2 release by respiring mitochondria and the decrease in the activities of the antioxidant enzymes glutathione peroxidase and reductase contributed to the reserpine effect on oxidative damage. The adrenaline effect is more difficult to explain, since the hormone increased the antioxidant enzyme activities but, in respiring mitochondria, increased ROS release rate in the presence of succinate and decreased it in the presence of pyruvate/malate. These opposite changes were due to the increased content of the autoxidizable electron carrier located at complex III and decreased content of that located at complex I. Our data suggest that adrenaline can be involved in the mitochondrial population adaptation which verify in conditions in which an increased body energy expenditure verify such as cold exposure.

Elsevier eBooks, 2021

Abstract This chapter describes the main processes by which mitochondria produce and manage react... more Abstract This chapter describes the main processes by which mitochondria produce and manage reactive species by eliminating them or allowing their use as signaling molecules. It starts by describing mitochondria as the sites of oxidative phosphorylation, which allows the ATP synthesis. It then depicts how mitochondria cause the formation of oxidant species (radicals and other reactive oxygen species, ROS) involved in diseases and aging. It also describes the mitochondrial antioxidant system and the main factors involved in its regulation. Besides, it illustrates how the antioxidant system allows mitochondria not only to protect themselves from oxidative damage but also to detoxify the ROS produced in other cellular sites, which renders mitochondria a sink of ROS. The information reported in this chapter highlights the importance of the mitochondrial antioxidant system that can affect the processes regulated by ROS such as cell signaling and metabolic and neurodegenerative disease progression.

Cellular Physiology and Biochemistry, 1998

This study was designed to investigate the possible oxidative changes associated with alterations... more This study was designed to investigate the possible oxidative changes associated with alterations in cytochrome P450 levels in rat liver. Accordingly, extent of peroxidative processes, cytochrome and antioxidant content, capacity to face an oxidative stress were determined in liver microsomes, mitochondria, and homogenates from normal and phenobarbital (PB)-treated rats. Liver content of microsomal and mitochondrial proteins was also determined by the values of the activities of marker enzymes (glucose-6-phosphatase and cytochrome oxidase, respectively) in liver homogenate and in two cellular fractions. The increase in the liver content of microsomal and mitochondrial proteins indicated that PB caused proliferation of both smooth endoplasmic reticulum and mitochondrial population. Treatment with PB also gave rise to a general increase in peroxidative reactions (evaluated measuring malondialdehyde and hydroperoxides (HPs)), in the different cell compartments, even though HPs were not found significantly increased in mitochondrial fraction. The increase in peroxidative processes was associated with significant decreases in antioxidant concentration (expressed in terms of equivalent concentration of an antioxidant, such as the desferrioxamine), in all preparations from PB-treated rats. The response to oxidative stress in vitro (evaluated determining the parameters characterizing light emission from preparations stressed with sodium perborate) showed a substantial PB-induced increase in the susceptibility to oxidative challenge only in liver homogenate. The lack of changes in the mitochondrial preparations is likely due to decrease in concentration of both free radical producing species and antioxidants. The lack of changes in microsomal fraction is apparently in contrast with its lower oxidant capacity and higher content of cytochromes which are able to determine sensitivity to pro-oxidants. However, it could be due to the ability of cytochrome P450 to interact with the active oxygen species formed at its active center.

Archives of Physiology and Biochemistry, 1995

A simple approach to quantitative determination of antioxidant capacity of rat liver homogenate i... more A simple approach to quantitative determination of antioxidant capacity of rat liver homogenate is proposed. It consists of measuring chemiluminescence generated by a suitable system &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot;detector&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot; for .OH radicals produced from sodium perborate. The system generating the light signal contained luminol and compounds producing enhancement of light emission, such as sodium benzoate and indophenol. Two different methods, utilizing the same technique of enhanced luminescence, were set up. In a previous work, a parameter b, contained in the equation, which best describes the dependence of the intensity of light emission (E) on liver homogenate concentration (C) (E = a.C/exp(b.C), was found to be related to the level of antioxidants in the homogenate. Therefore, in the first method, the light emission from several dilutions of both liver homogenates, and homogenate and antioxidant mixtures, stressed with sodium perborate, was detected by a luminometer. The best fitting of data to theoretical equation provided b values, which were introduced in a system of equations relating such values to the antioxidant concentration. The solution of above system supplied the antioxidant concentration in the homogenate in terms of the equivalent concentration of the antioxidant used. In the other method, evaluations of the antioxidant capacity of liver homogenates were obtained by the determination of the ability of 10% homogenates to quench the light emission induced by either peroxidase or cytochrome c in comparison to the ability of antioxidant solutions. Both methods are able to evidence the decrease of the antioxidant concentration of liver homogenates after oxidative stress with ter-butylhydroperoxide. The value of both concentration changes and standard errors indicates that the method using a standard curve obtained with peroxidase, such as catalyst of radical reaction, and deferoxamine, such as antioxidant, is to be preferred.

Nutrients, Dec 1, 2019

Mitochondria are both the main sites of production and the main target of reactive oxygen species... more Mitochondria are both the main sites of production and the main target of reactive oxygen species (ROS). This can lead to mitochondrial dysfunction with harmful consequences for the cells and the whole organism, resulting in metabolic and neurodegenerative disorders such as type 2 diabetes, obesity, dementia, and aging. To protect themselves from ROS, mitochondria are equipped with an efficient antioxidant system, which includes low-molecular-mass molecules and enzymes able to scavenge ROS or repair the oxidative damage. In the mitochondrial membranes, a major role is played by the lipid-soluble antioxidant vitamin E, which reacts with the peroxyl radicals faster than the molecules of polyunsaturated fatty acids, and in doing so, protects membranes from excessive oxidative damage. In the present review, we summarize the available data concerning the capacity of vitamin E supplementation to protect mitochondria from oxidative damage in hyperthyroidism, a condition that leads to increased mitochondrial ROS production and oxidative damage. Vitamin E supplementation to hyperthyroid animals limits the thyroid hormone-induced increases in mitochondrial ROS and oxidative damage. Moreover, it prevents the reduction of the high functionality components of the mitochondrial population induced by hyperthyroidism, thus preserving cell function.

Free Radical Research, Jul 22, 2014

Aim of the present study was to test, by vitamin E treatment, the hypothesis that muscle adaptive... more Aim of the present study was to test, by vitamin E treatment, the hypothesis that muscle adaptive responses to training are mediated by free radicals produced during the single exercise sessions. Therefore, we determined aerobic capacity of tissue homogenates and mitochondrial fractions, tissue content of mitochondrial proteins and expression of factors (PGC-1, NRF-1, and NRF-2) involved in mitochondrial biogenesis. Moreover, we determined the oxidative damage extent, antioxidant enzyme activities, and glutathione content in both tissue preparations, mitochondrial ROS production rate. Finally we tested mitochondrial ROS production rate and muscle susceptibility to oxidative stress. The metabolic adaptations to training, consisting in increased muscle oxidative capacity coupled with the proliferation of a mitochondrial population with decreased oxidative capacity, were generally prevented by antioxidant supplementation. Accordingly, the expression of the factors involved in mitochondrial biogenesis, which were increased by training, was restored to the control level by the antioxidant treatment. Even the training-induced increase in antioxidant enzyme activities, glutathione level and tissue capacity to oppose to an oxidative attach were prevented by vitamin E treatment. Our results support the idea that the stimulus for training-induced adaptive responses derives from the increased production, during the training sessions, of reactive oxygen species that stimulates the expression of PGC-1, which is involved in mitochondrial biogenesis and antioxidant enzymes expression. On the other hand, the observation that changes induced by training in some parameters are only attenuated by vitamin E treatment suggests that other signaling pathways, which are activated during exercise and impinge on PGC-1, can modify the response to the antioxidant integration.

Neurosignals, 2001

In recent years it has been suggested that reactive oxygen species (ROS) are involved in the dama... more In recent years it has been suggested that reactive oxygen species (ROS) are involved in the damage to muscle and other tissues induced by acute exercise. Despite the small availability of direct evidence for ROS production during exercise, there is an abundance of literature providing indirect support that oxidative stress occurs during exercise. The electron transport associated with the mitochondrial respiratory chain is considered the major process leading to ROS production at rest and during exercise. It is widely assumed that during exercise the increased electron flow through the mitochondrial electron transport chain leads to an increased rate of ROS production. On the other hand, results obtained by in vitro experiments indicate that mitochondrial ROS production is lower in state 3 (ADP-stimulated) than in state 4 (basal) respiration. It is possible, however, that factors, such as temperature, that are modified in vivo during intense physical activity induce changes (uncoupling associated with loss of cytochrome oxidase activity) leading to increased ROS production. The mitochondrial respiratory chain could also be a potential source of ROS in tissues, such as liver, kidney and nonworking muscles, that during exercise undergo partial ischemia because of reduced blood supply. Sufficient oxygen is available to interact with the increasingly reduced respiratory chain and enhance the ROS generation. At the cessation of exercise, blood flow to hypoxic tissues resumes leading to their reoxygenation. This mimics the ischemia-reperfusion phenomenon, which is known to cause excessive production of free radicals. Apart from a theoretical rise in ROS, there is little evidence that exercise-induced oxidative stress is due to its increased mitochondrial generation. On the other hand, if mitochondrial production of ROS supplies a remarkable contribution to exercise-induced oxidative stress, mitochondria should be a primary target of oxidative damage. Unfortunately, there are controversial reports concerning the exercise effects on structural and functional characteristics of mitochondria. However, the isolation of mitochondrial fractions by differential centrifugation has shown that the amount of damaged mitochondria, recovered in the lightest fraction, is remarkably increased by long-lasting exercise.

Antioxidants, Feb 27, 2023

This article is an open access article distributed under the terms and conditions of the Creative... more This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY

Comparative biochemistry and physiology. B. Comparative biochemistry, Aug 1, 1992

Surface antigens of B. bubalis spermatozoa were solubilized by Triton X-100 and EDTA; the sperm e... more Surface antigens of B. bubalis spermatozoa were solubilized by Triton X-100 and EDTA; the sperm extract was used to raise antibodies in rabbits. 2. Two major polypeptides, immunoprecipitated from the seminal plasma by the antibodies against the sperm extract, exhibited the same electrophoretic mobilities of two immunorelated sperm surface antigens. 3. The two polypeptides were isolated from the seminal plasma, by a multi-step chromatographic procedure, and found subunits of a single protein (MW 30,000), called SP 30. 4. The SP 30 protein bound in vitro to the postacrosomal region of homologous spermatozoa from cauda epididymis. 5. The localization of the sperm-coating antigen on the cell surface is compatible with a role in the fertilization process.

Oxygen, Sep 14, 2022

Cellular and Molecular Life Sciences, Jun 1, 1996

Oxidative Medicine and Cellular Longevity, 2014

Archives of Biochemistry and Biophysics, Mar 1, 2003

The purpose of this study was to investigate the effects of thyroid state on rates and sites of H... more The purpose of this study was to investigate the effects of thyroid state on rates and sites of H 2 O 2 production in rat muscle mitochondria. With Complex I-and Complex II-linked substrates, hypothyroidism decreased and hyperthyroidism increased the rates of O 2 consumption during State 4 and State 3 respiration and the rates of H 2 O 2 release during State 4 respiration. During State 3, the rates of H 2 O 2 release were not affected by thyroid state. However, the mitochondrial capacity to remove H 2 O 2 increased in the transition from hypothyroid to hyperthyroid state, thus suggesting that an increase in H 2 O 2 production rate also occurred in such a transition during State 3 respiration. The observation that mitochondrial coenzyme Q levels and cytochrome oxidase activities are higher in the hyperthyroid and lower in the hypothyroid groups suggests that the modifications of H 2 O 2 production are due to a modulation by thyroid hormone of the mitochondrial content of autoxidizable electron carriers. This idea is supported by measurements of H 2 O 2 release in the presence of respiratory inhibitors. In fact, such measurements indicate that the thyroid state-linked changes in H 2 O 2 production occur at both generator sites of the respiratory chain.

Hormone and Metabolic Research, 2003

This work was designed to determine possible effects of altered thyroid states on rates and sites... more This work was designed to determine possible effects of altered thyroid states on rates and sites of H 2 O 2 production by rat heart mitochondria. Rates of O 2 consumption and H 2 O 2 release, capacities to remove the peroxide, lipid peroxidation, cytochrome oxidase activities and ubiquinone levels were determined in heart mitochondria from euthyroid, hypothyroid, and hyperthyroid rats. Hypothyroidism decreased, whereas hyperthyroidism increased the rates of O 2 consumption and H 2 O 2 release during both state 4 and state 3 respiration with Complex I- or Complex II-linked substrates. The percentage of O 2 released as H 2 O 2 was not significantly affected by thyroid state. However, the mitochondrial capacity to remove H 2 O 2 increased in the transition from hypothyroid to hyperthyroid state, which indicates that H 2 O 2 production did not modify in proportion to the rate of O 2 consumption. The thyroid-state-linked changes in H 2 O 2 production were well correlated with the levels of hydroperoxides. Rates of H 2 O 2 release in the presence of respiratory inhibitors indicated that changes in the H 2 O 2 production occurred at both sites at which H 2 O 2 was generated in euthyroid state. This result and the observation that ubiquinol levels and cytochrome oxidase activities increase in the transition from hypothyroid to hyperthyroid state suggest that the modifications of H 2 O 2 production are due to a modulation by thyroid hormone of mitochondrial content of autoxidisable electron carriers.

Cardiovascular Research, Oct 1, 2002

Objective: We investigated the effect of hyperthyroidism on the functional response of mitochondr... more Objective: We investigated the effect of hyperthyroidism on the functional response of mitochondria to ischemia-reperfusion and its relationship with changes in mitochondrial susceptibility to stress conditions. Methods: Hyperthyroidism was elicited by ten daily intraperitoneal injections of T (10 mg / 100 g body weight). Mitochondria were isolated at 30003g (M) from homogenates of hearts 3 3 perfused by the Langendorff technique after either 25 min reperfusion following 20 min ischemia or 45 min perfusion (controls). Rates of O consumption and H O release with complex II-linked substrate, capacity to remove H O , extent of oxidative damage, levels of 2 2 2 2 2 21 liposoluble antioxidants, such as ubiquinols and vitamin E, and susceptibility to Ca-induced swelling were determined. Results: During reperfusion, hyperthyroid hearts displayed a significant tachycardia together with a low functional recovery. In comparison to the respective controls, mitochondria from both euthyroid and hyperthyroid hearts subjected to ischemia-reperfusion protocol exhibited decreases in the rate of O consumption, capacity to remove H O , and concentration of antioxidants, and increases in the rate of H O 2 2 2 2 2 21 release, concentration of hydroperoxides and protein-bound carbonyls, and susceptibility to Ca-induced swelling. Such changes were higher in mitochondria from hyperthyroid hearts. The increase in the protein percent content and cytochrome oxidase activity of a mitochondrial fraction isolated at 80003g (M) from hyperthyroid hearts after reperfusion, suggests that the decline of mitochondrial 8 respiration of M fraction could be due to the degradation of the oldest, mature mitochondria endowed of high oxidative capacity, but low 3 antioxidant capacity, which would be lost by heavy mitochondrial fraction and recovered in the light fraction. Conclusions: The higher susceptibility to ischemia-reperfusion of the heart from hyperthyroid animals is associated with a significant increase in mitochondrial dysfunction.

Molecular and Cellular Endocrinology, Jul 1, 2011

Thyronamines reduce the in vitro mitochondrial oxygen consumption. Thyronamines increase the in v... more Thyronamines reduce the in vitro mitochondrial oxygen consumption. Thyronamines increase the in vitro mitochondrial hydrogen peroxide oxygen release. Thyronamine are oxidized by mitochondrial monoamine oxydase. Inhibition of monoamine oxydase reduces thyronamine induced increase in H 2 O 2 release. Thyronamines reduce the activity of complex III of the respiratory chain.

Cellular Physiology and Biochemistry, 1999

Whole mitochondrial population and three mitochondrial fractions were resolved by differential ce... more Whole mitochondrial population and three mitochondrial fractions were resolved by differential centrifugation from liver homogenates from euthyroid, hyperthyroid (ten daily i.p. injections of triiodothyronine (T3), 10 microg/100 g body weight) and hyperthyroid vitamin E-treated (ten daily i.m. vitamin E injections, 20 mg/100 g body weight) rats. Homogenates and mitochondrial preparations were examined for their protein content, oxidative capacity, lipid peroxidation, antioxidant status, and susceptibility to oxidative stress. In all groups, antioxidant level was smaller and oxidative capacity, lipid peroxidation, and susceptibility to oxidants were greater in the heavy mitochondrial fraction. T3 treatment was associated with increased oxidative capacity, lipid peroxidation, and susceptibility to oxidative stress, and decreased antioxidant levels in all preparations. It was also associated with increased mitochondrial protein content of homogenate and altered quantitative presence of the mitochondrial fractions. The vitamin E effects on the T3-induced changes were different for the different parameters. Vitamin E did not modify the mitochondrial protein content in liver and oxidative capacity of the various preparations, reduced the changes in both susceptibility to oxidants and contribution of each fraction to the whole mitochondrial population, and reinstated euthyroid values for antioxidant capacity and lipid peroxidation. The incomplete recovery of euthyroid resistance to oxidants in vitamin E-treated rats is due to the vitamin inability to reinstate the levels of both antioxidants and hemoproteins, on which such a resistance depends. The vitamin E effect on the composition of the mitochondrial population is more difficult to explain, because of the complexity of the mechanisms underlying the mitochondrial population modulation by thyroid hormone. However, available data suggest that such a modulation occurs through changes in the turnover of the mitochondrial fractions to which an induction of mitochondrial protein synthesis and accelerated antioxidant-sensitive degradation contribute in different measure.

International Journal of Molecular Sciences, Mar 21, 2020

Currently, it is known that, in living systems, free radicals and other reactive oxygen and nitro... more Currently, it is known that, in living systems, free radicals and other reactive oxygen and nitrogen species play a double role, because they can cause oxidative damage and tissue dysfunction and serve as molecular signals activating stress responses that are beneficial to the organism. It is also known that mitochondria, because of their capacity to produce free radicals, play a major role in tissue oxidative damage and dysfunction and provide protection against excessive tissue dysfunction through several mechanisms, including the stimulation of permeability transition pore opening. This process leads to mitoptosis and mitophagy, two sequential processes that are a universal route of elimination of dysfunctional mitochondria and is essential to protect cells from the harm due to mitochondrial disordered metabolism. To date, there is significant evidence not only that the above processes are induced by enhanced reactive oxygen species (ROS) production, but also that such production is involved in the other phases of the mitochondrial life cycle. Accumulating evidence also suggests that these effects are mediated through the regulation of the expression and the activity of proteins that are engaged in processes such as genesis, fission, fusion, and removal of mitochondria. This review provides an account of the developments of the knowledge on the dynamics of the mitochondrial population, examining the mechanisms governing their genesis, life, and death, and elucidating the role played by free radicals in such processes.

Cellular and Molecular Life Sciences, Sep 1, 2001