Biomedical subjects

François Criscuolo

Publications and source records attributed to François Criscuolo.

10 recordsLinked to original sources

PubMed2007

Mitochondria contribute to LPS-induced MAPK activation via uncoupling protein UCP2 in macrophages.

The mitochondrion is a major organelle contributing to energy metabolism but also a main site of ROS (reactive oxygen species) production. LPS (lipopolysaccharide)-induced ROS signalling is a critical event in macrophage activation. In the present paper we report that part of LPS-mediated ROS signalling comes from mitochondria inside a signal amplification loop that enhances MAPK (mitogen-activated protein kinase) activation. More precisely, we have identified the inner mitochondrial membrane UCP2 (uncoupling protein 2) as a physiological brake on ROS signalling. Stimulation of murine bone marrow-derived macrophages by LPS quickly down-regulated UCP2 through the JNK (c-Jun N-terminal kinase) and p38 pathways. UCP2 down-regulation was shown to be necessary to increase mitochondrial ROS production in order to potentiate MAPK activation. Consistent with this, UCP2-deficient macrophages exhibit an enhanced inflammatory state characterized by increased nitric oxide production and elevated migration ability. Additionally, we found that the absence of UCP2 renders macrophages more resistant to nitric oxide-induced apoptosis.

Animals↗

PubMed2006

Innate immunity, assessed by plasma NO measurements, is not suppressed during the incubation fast in eiders.

Immunity is hypothesized to share limited resources with other physiological functions and may mediate life history trade-offs, for example between reproduction and survival. However, vertebrate immune defense is a complex system that consists of three components. To date, no study has assessed all of these components for the same animal model and within a given situation. Previous studies have determined that the acquired immunity of common eiders (Somateria mollissima) is suppressed during incubation. The present paper aims to assess the innate immune response in fasting eiders in relation to their initial body condition. Innate immunity was assessed by measuring plasma nitric oxide (NO) levels, prior to and after injection of lipopolysaccharides (LPS), a method which is easily applicable to many wild animals. Body condition index and corticosterone levels were subsequently determined as indicators of body condition and stress level prior to LPS injection. The innate immune response in eiders did not vary significantly throughout the incubation period. The innate immune response of eiders did not vary significantly in relation to their initial body condition but decreased significantly when corticosterone levels increased. However, NO levels after LPS injection were significantly and positively related to initial body condition, while there was a significant negative relationship with plasma corticosterone levels. Our study suggests that female eiders preserve an effective innate immune response during incubation and this response might be partially determined by the initial body condition.

Animals↗

PubMed2006

UCP2, UCP3, avUCP, what do they do when proton transport is not stimulated? Possible relevance to pyruvate and glutamine metabolism.

Uncoupling proteins (UCPs) are specialized members of the mitochondrial transporter family. They allow passive proton transport through the mitochondrial inner membrane. This activity leads to uncoupling of mitochondrial respiration and to energy waste, which is well documented with UCP1 in brown adipose tissue. The uncoupling activity of the new UCPs (discovered after 1997), such as UCP2 and UCP3 in mammals or avUCP in birds, is more difficult to characterize. However, extensive data support the idea that the new UCPs are involved in the control of reactive oxygen species (ROS) generation. This fits with the hypothesis that mild uncoupling caused by the UCPs prevents ROS production. Activators and inhibitors regulate the proton transport activity of the UCPs. In the absence of activators of proton transport, the UCP allows the permeation of other ions. We suggest that this activity has physiological significance and, for example, UCP3 expressed in glycolytic muscle fibres may be a passive pyruvate transporter ensuring equilibrium between glycolysis and oxidative phosphorylation. Induction of UCP2 expression by glutamine strengthens the proposal that new UCPs could act to determine the choice of mitochondrial substrate. This would obviously have an impact on mitochondrial bioenergetics and ROS production.

Animals↗

PubMed2006

Fasting-induced changes of immunological and stress indicators in breeding female eiders.

One adaptive significance of immunosuppression during reproduction can be explained by the immunopathology-avoidance hypothesis. This hypothesis states that since heat shock proteins (HSP) are highly conserved proteins found in both pathogen and host, and are expressed at a higher level during reproduction, the risk of autoimmunity is then increased, HSP being the target of the host's immune response. Reduced immunocompetence has been attributed to hormonal regulation, in particular by glucocorticoids. The current study aimed at testing the immunopathology-avoidance hypothesis and the implication of corticosterone in incubating fasting common eiders (Somateria mollissima). To this end, we have measured immunological and stress indicators including immunoglobulin (IgY), HSP70, HSP60, and corticosterone levels in breeding females. A multivariate general linear model analysis showed that female body condition, IgY, HSP70, and HSP60 levels were the main variables explaining the model. Females showed a significant decrease by 15% of their IgY index during incubation. Conversely, HSP70 and HSP60 levels significantly increased by 12 and 10%, respectively throughout incubation. Moreover, there was a positive significant relationship between both HSP whereas HSP60 levels were negatively correlated to IgY index. Plasma corticosterone levels showed a tendency to decrease during incubation. We conclude that these findings are consistent with the immunopathology-avoidance hypothesis in breeding eiders. Nevertheless, the long-term reproductive costs and the underlying mechanisms of such an immunosuppression remain to be determined and will require further experiments.

Animals↗

PubMed2005

Mitochondrial uncoupling proteins: new perspectives for evolutionary ecologists.

Reactive oxygen species (ROS)-induced damage on host cells and molecules has been considered the most likely proximal mechanism responsible for the age-related decline in organismal performance. Organisms have two possible ways to reduce the negative effect of ROS: disposing of effective antioxidant defenses and minimizing ROS production. The unbalance between the amount of ROS produced and the availability of antioxidant defenses determines the intensity of so-called oxidative stress. Interestingly, most studies that deal with the effect of oxidative stress on organismal performance have focused on the antioxidant defense compartment and, surprisingly, have neglected the mechanisms that control ROS production within mitochondria. Uncoupling proteins (UCPs), mitochondrial transporters of the inner membrane, are involved in the control of redox state of cells and in the production of mitochondrial ROS. Given their function, UCPs might therefore represent a major mechanistic link between metabolic activity and fitness. We suggest that by exploring the role of expression and function of UCPs both in experimental as well as in comparative studies, evolutionary biologists may gain better insight into this link.

Aging↗

PubMed2005

Avian uncoupling protein expressed in yeast mitochondria prevents endogenous free radical damage.

The longevity of birds is surprising since they exhibit high metabolic rates and elevated blood sugar levels compared with mammals of the same body size, which presumably expose them to higher rates of free oxygen radical production, which is implicated in accelerated senescence. Uncoupling proteins (UCPs) are transporters of the inner mitochondrial membrane and their physiological activity is still a subject of debate. Avian UCP was found in birds but data on its activity are scarce. Avian UCP (Gallus gallus) was overexpressed in yeast and we assessed its ability to prevent mitochondrial reactive oxygen species (ROS) production by measuring ROS damage (aconitase activity) and antioxidant defences (MnSOD activity). We show that avian UCP protects yeast mitochondria against the deleterious impact of ROS, but without stimulation of superoxide dismutase activity. Avian UCP protein was specifically immunodetected and retinoic acid, which belongs to the carotenoid family, was found to trigger its activity. These data show that avian UCP basal activity protects against ROS damage. However, when activated by retinoic acid, avian UCP can also operate as the mammalian thermogenic UCP1. The hypothesis that avian UCP activities are state- and species-dependent is further discussed.

Aconitate Hydratase↗

PubMed2003

Differences in the expression of lipolytic-related genes in rat white adipose tissues.

We have investigated in vivo whether the gene expression of the beta3-adrenergic receptor (beta3-AR), perilipin A, hormone-sensitive lipase (HSL), and adipocyte lipid-binding protein (ALBP/aP2) is regulated in a site-specific manner. To induce lipolysis and discriminate between short- and long-term modifications, rats were submitted to an experimental fast for one or five days followed or not by refeeding. The mRNA encoding beta3-AR in retroperitoneal adipose tissue (RP) was significantly increased by one and five days of fasting (4-fold) and then lowered by one day of refeeding (2-fold) compared to fed rats. The reverse trend was observed for perilipin A expression in one day fasted rats. HSL mRNA concentrations were significantly induced (2.2-fold) by five days of fasting relative to fed animals and remained high after refeeding. ALBP/aP2, peroxisome proliferator-activated receptor gamma, and CAAT/enhancer binding protein alpha mRNA levels were essentially unaffected by dietary manipulations. Fasting and/or refeeding were similarly ineffective at regulating gene expression in SC. These data provide a molecular basis for regional differences at different steps of the lipolytic process.

Adipose Tissue↗

PubMed2003

Hypothalamic gene expression in long-term fasted rats: relationship with body fat.

Many hypothalamic neuropeptides are involved in the regulation of energy homeostasis and feeding behavior. We have investigated whether and to what extent neuropeptide Y (NPY), agouti-related protein (AGRP), melanin-concentrating hormone (MCH), and prepro-orexin (prepro-OX) as well as pro-opiomelanocortin (POMC) and cocaine and amphetamine-regulated transcript (CART) mRNA levels are affected in rat hypothalamus. An experimental model of long-term fasting rat characterized by three metabolic phases from changes in lipid and protein utilization was used. Except for prepro-OX and compared to fed group, starvation induced an increase in the orexigenic gene expressions that was much more marked in phase 3 (by 2.5-, 8.1-, and 13.5-fold for MCH, AGRP, and NPY, respectively) than in phase 2 (by about 1.5-2.2-fold as an average) of fasting. AGRP and NPY mRNA levels were inversely related to body fat content. Anorexigenic gene expression was only slightly affected at both fasting stages. We conclude that the regulation of NPY and AGRP gene expression is primarily involved during late fasting and could mediate the concomitant enhanced drive for refeeding.

Adipose Tissue↗

PubMed2002

Factors affecting plasma concentrations of prolactin in the common eider Somateria mollissima.

In the common eider only the females incubate while they fast for 25 days. Thus, since they rely entirely on their body reserves for successful incubation, they can be defined as capital incubators. To assess the potential effects of their initial body mass, the incubation duration, and depletion in body reserves on prolactinemia, blood samples of eiders were analyzed during the breeding cycle and an experimental manipulation of the duration of incubation. Levels of circulating prolactin increased at the onset of incubation and then reached a high and stable level during incubation before increasing sharply before hatching. The prolactin level decreased significantly upon hatching. Captive females deprived from their eggs exhibited a rapid decrease in prolactinemia, suggesting that egg stimuli are necessary to prolactin secretion. Aunts, i.e., helper females caring for conspecific young, presented prolactin levels higher than nonbreeding captive females but not significantly different from those of females at hatching. Plasma prolactin at hatch was directly related to body mass loss. Birds with shortened incubation have higher body masses and showed higher levels of prolactinemia at hatching than the control group, in accordance with the idea that circulant prolactin at hatching is linked to body condition. Females which underwent an extended incubation (and started to eat again) displayed a low body mass and a high prolactinemia. These data therefore suggest that refeeding, albeit increasing the risk of predation, enhances prolactin secretion and allows the bird to continue incubation despite that it has reached a poor body condition.

Animals↗

PubMedDate not supplied

Do T3 levels in incubating eiders reflect the cost of incubation among clutch sizes?

Complete development of avian eggs requires external heat, inducing in most species an energetic cost of incubation for the parents. Triiodothyronine (T(3)) has been implicated in the control of the metabolic rate and is decreased during fasting in most bird species. This raises the question of the regulation of T(3) during reproduction when incubation (thus heat production) is associated with fasting (and energy sparing). In this study, plasma concentrations of T(3) were studied for different clutch sizes in incubating, as well as in nonincubating, fasting female eiders. Our results show that the T(3) levels decrease during fasting in nonincubating birds, whereas they were maintained during the incubation fast. T(3) levels increased in female eiders at hatching. The plasma T(3) level did not vary among natural clutch sizes in eiders but did so when manipulated. T(3) levels increased when eggs were added (to a maximum of six eggs, i.e., the biggest natural clutch size) or removed (to two eggs, i.e., the smallest natural clutch size). Our results suggest that (1) high T(3) levels during incubation may participate to a threshold of heat production and incubation metabolic rate in eiders despite the fact that they are fasting; (2) since T(3) is associated with the energy expenditure in birds, incubating an enlarged or reduced clutch size may lead to a higher energetic cost of incubation in eiders; and (3) the energy demand of the ducklings at hatching is probably important, as the female T(3) concentrations are then at their highest levels. Thus, any modification of the natural clutch size leads to a rise in the T(3) level of the incubating female, suggesting an additional cost of incubation. Knowing that there is no variation of T(3) levels among natural clutch sizes, this study suggests that a female eider produces a number of eggs corresponding to the energy she can invest in incubation.

Analysis of Variance↗