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Sufficiency perspective involves a new and deep re-examination of individual moral principles such as the personal values system in the time of environmental crisis. To illustrate, it seems to be evidence of an urge to follow the guideline of moral and ethical dimensions of consumption, supporting social and wellbeing standards for all individuals taking into account the planetary boundaries. More specifically, it is recommended that, in the future, the transition towards the achievement of sufficiency models should be devoted to the area of complex concepts that bring together upper and lower limits of resources consumption, also named consumption corridors.

There is increasing interest toward insects as an alternative protein source in Western countries even though, so far, most Western consumers react with disgust and rejection. The literature on consumer behavior has mainly investigated the willingness to consume insects with regard to human diet, revealing that providing information about the positive effects of edible insects and using familiar foods while ensuring that insects are not visible will increase the willingness to eat insects. What is still unclear are consumers preferences for specific insect-based products having different features in a non-hypothetical market. The current study analyzed 200 Italian consumers’ preferences for three insect-based products (carriers) such as pasta, cookies and chocolate bars through a non-hypothetical willingness to pay (WTP) elicitation mechanism, the Multiple Price List (MPL), in a mixed within/between experimental design. The influence of the different types of information on consumer choice and the main forces driving consumer preferences for insect-based food were tested. The findings reveal that different carriers generate different results in terms of WTP for conventional and insect-based versions of the products. Further, without being provided information, consumers deem insect-based products either equivalent (the same WTP for the two versions of pasta) or weakly inferior (lower WTP in the case of cookies and chocolate), while when information on the benefits of insect consumption is provided, consumers’ WTP increase for all the insect-based products analyzed. Finally, among the psychographic scales, Food Neophobia and Beliefs and Attitudes toward insects negatively affect the WTP for insect-based products.

Implementing circular business models in food supply chains is an organizational solution to tackle the issue of household food waste, converting it in feedstock to upcycle within industrial symbioses.Adopting literature on practices of food consumption as theoretical framework, this paper analyzes consumers’ participation in circular business models. A conceptual model of the emergence of food provisioning practices in circular business models is designed and empirically tested, through a survey, in order to analyze consumers’ willingness to participate in an innovative food provisioning mechanism with retailers. Respondents were asked to choose whether to participate or not in a proposed program, and their choices have been modelled in an ordered logit model. 88% of interviewees declared sorting organic food waste as a normal activity in his household. 78.9% of participants accepted to participate to the proposed programs independently of the type of agreement’s attributes. 14.49% accepted only some programs depending on the program type, while 6.61% of respondents choose not to participate to any of the proposed program. Findings outline the expected participant as an individual already engaged in tasks to cope with risk in food provisioning and having already developed a long-lasting relation with a retailer. The study reveals also the opposite effect of concerns about tasks related to take-back system, such as food waste handling, and social desirability of recycling. Focusing on the business-to-consumers relationship, the paper suggests to practitioners interested in circular business models the possibility to adopt innovative ‘food-product-as-a-service’ approaches. Recommendations can be derived for future studies about the relevance of practice theory in the analysis of consumers’ engagement in circular business models.

Health claims have been introduced in food labelling to support consumers’ awareness of healthy food choices and to enhance a healthy diet. Even though many countries around the world have developed legislation and guidelines to regulate the introduction of health claims on food labels, there is the evidence that many consumers do not understand the meaning of these claims. This study analyses whether Italian consumers really understand authorized health claims on extra-virgin olive oil and what are the drivers of such understanding. An Olive Oil Health Claims Understanding index was constructed and embedded in a structured questionnaire, which was then administered to a representative sample of Italian household members who are responsible for food shopping (N = 1,030). Results from the survey showed that only 36% of the respondents understood the meaning of the authorized health claims on extra-virgin olive oil. Moreover, the findings confirmed that the understanding of health claims is related to socio-demographic, personal and psychographic characteristics of consumers, as well as to their attitudes toward using food as medicine. Outcomes also proved the central role of nutrition knowledge in affecting understanding of health claims.

Animal welfare involves societal and human values, ethical concerns and moral considerations since it incorporates the belief of what is right or what is wrong in animal treatment and care. This paper aims to ascertain whether the different dimensions of individual attitudes toward animal welfare in food choices may be characterized by general human values, as identified by Schwartz. For this purpose, an EU-wide survey was carried out, covering almost 2500 nationally representative individuals from five European countries. Compared with the previous literature this study shows a twofold novelty: (1) it develops a general framework to link individual enduring beliefs and attitudes toward animal welfare attributes in food choices; (2) the framework is analyzed within a broad-based cross-country study. Our empirical results prove that human values related to self-transcendence are strongly associated to overall animal welfare attitudes and especially to those explicitly related to food choices, while values related to the spheres of self-enhancement and conservatism are significantly associated to less sensitive attitudes to animal welfare. Moreover, our results appear to indicate that a determinant of animal welfarism in food choices is potentially associated to individual concerns regarding food safety issues.

Among foods with credence attributes, food with “natural” components have received in the last years particular attention by consumers. This study applies the BDM incentive compatible mechanism to explore young (18–35 years old) consumers’ interest and willingness to pay for chewing gums having the natural attribute. Our analysis shows that over 68% of consumers are interested in the natural attribute and are willing to pay a price premium. We also find that consumers’ higher age and interest in the environment have significant impacts on consumers’ preferences for the natural attribute.

Why are consumers increasingly participating in alternative food chains to co-produce and distribute foods with farmers? In this paper, values and food-related lifestyles, as well as transaction costs and socio-demographics, are used to analyze consumer participation in alternative food chains in Italy. Using a simultaneous system of equations, a model with instrumental variables is implemented to measure the relationships between values and food-related lifestyles, and between the latter and participation in an alternative food chain. Our results show that Italian participants in alternative food chains have the profile of rational shoppers who typically look at price and taste criteria. Although transaction costs do not affect participation directly, they do so through food-related lifestyles.

The current linear system of production and consumption is unsustainable. In the food sector, despite the fact that valuable natural resources are intensively used to produce and distribute food products, little is done to upcycle residues generated along the supply chain. Circular economy strategies are crucial for restructuring the take-make-dispose model through the active participation of all actors of supply chains. However, little is known about consumers’ willingness to participate in circular economy. A structured questionnaire was submitted to a representative sample of Italian households to assess the willingness of consumers to be actively involved in closed loops aiming at reducing food waste. Consumers are involved by returning their organic food waste to retailers in exchange for discounts on the purchase of animal products. The organic food waste returned enters in the production process of animal products. A choice experiment was designed to analyse alternative programs. Two scenarios were presented: one with a traditional technology (composting), and a second one with a radically innovative technology (insects as feed). Preferences and trade-offs, in monetary terms, among attributes were computed. Results depict a comprehensive portrait of the potential participation of consumers to closed loops inspired by the principles of circular economy.

The present study focused on an environmental scandal that occurred in Italy, the Land of Fires toxic waste scandal, which caused consumer concerns related to the safety of food produced in the affected region, as well as massive market reduction in products associated with the polluted area. Based on a representative sample of Italian households (N = 1134), this study applied an extended Theory of Planned Behavior (TPB) model to analyze consumer purchases of regional food products after this environmental hazard. In addition to attitudes, subjective norms and perceived behavioral control, the model included risk perception, trust, and actual purchases. Using a structural equation model, our results provided support to the hypothesis that consumer perceptions of risk negatively impacted their purchase behaviors and suggested that increasing Italians&rsquo, trust in government information could reduce their perceived risk and, consequently, increase their intention to purchase regional food.

In the wake of highly volatile world prices of staple commodities, we examine the impacts of increases in maize prices on various categories of households in Malawi. Using household-level data, changes in household income are calculated taking into account the net maize production status of the household and food price elasticities estimated from a censored demand system. While maize price increases have unequivocal deleterious effects on the incomes of urban households, rural households experience differential impacts. Net producing households in rural areas benefit from price increases with households above the poverty line obtaining proportionally higher incomes.

Background: N-linked glycosylation, which is a post-translational modification process, plays an important role in protein folding, intracellular trafficking and membrane targeting, as well as in regulating the protein function. Recently, we identified a missense variant (p.T141L) in the short isoform 2 of the X-linked gene asparagine-linked glycosylation 13 (ALG13-is2), which segregated with focal segmental glomerulosclerosis and PCCD in a large Australian pedigree; however, any evidence of its pathogenicity was demonstrated. ALG13 gene encodes, through alternative splicing, 2 glycosyltransferase isoforms, which catalyse the second sugar addition of the highly conserved oligosaccharide precursor in the endoplasmic reticulum (ER). Mutations in the long isoform 1 were associated with epilepsy. Methods and Results: Here, we show a different expression of the 2 isoforms depending on the tissue. Specifically, the long isoform is highly expressed in lungs, ovaries, testes, cerebellum, cortex, retina, pituitary gland, and olfactory bulbs, while the short isoform is highly expressed in mouse podocytes and in human podocyte cell lines, at both mRNA and protein levels. The silencing of ALG13-is2 by specific siRNAs induces an altered N-linked glycosylation pattern of nephrin, as demonstrated by the presence of an additional immunostaining band of about 130 kD. In knock-down cells, immunofluorescence analysis shows perturbed organization of the cytoskeleton and altered localization of nephrin on the cellular membrane. We also demonstrated that the altered pattern of N-linked glycosylation induces an over-expression of binding immunoglobulin protein and calreticulin, suggesting ER stress. Conclusions: These results provide preliminary evidence that ALG13-is2 could be an important modifier of renal filtration defects.

In this paper we investigate values and transaction conditions in consumer participation in alternative food networks (AFNs). We use and combine a collective action perspective with elements of ethical consumption (individual values) and transaction cost economics as a theoretical background to conceptualise this participation. Our research is motivated by the evidence that the role and interplay between values and transaction conditions is still under-investigated in the socio-economic literature when it comes to understanding participation in AFNs. We use a case study in which we focus on an AFN located in Palermo, a metropolitan area in southern Italy. We collected data related to 303 individuals: 103 participants in the AFN and 200 non-participants. From a methodological perspective we used a propensity score matching approach. We were thus able to build a subsample consisting of only those individuals who were sharing a similar likelihood of participating in an AFN. Individuals with the same propensity score show a substantial equivalence in terms of covariates as if they were randomly selected to join an AFN. Our results indicate a statistically significant difference in some transactional conditions for AFN participants. Namely, when it comes to transactional conditions associated to food purchasing strategies, participants in AFNs are characterised by a higher level of (perceived) information uncertainty (e.g. price uncertainty and product information), negotiation uncertainty (e.g. relevance of the speed of sourcing, transportation hazards, and bargaining), and monitoring hazards (e.g. quality uncertainty), when compared to non-participants. These results are used to account for the heterogeneity of participants in SPGs in particular, and AFNs in general.

Purpose Consumer interest and willingness to pay (WTP) for omega-3 enriched water buffalo mozzarella cheese are evaluated through an in-store experimental auction. The purpose of this paper is to estimate individual WTP for enriched mozzarella cheese and related it to self-efficacy beliefs and outcome expectations of omega-3 consumption, following regulatory focus theory. Design/methodology/approach Data were collected in May-June 2015 from a sample of 150 consumers in Southern Italy. A structural equation modelling procedure was implemented. Findings The results show a significant role is played by prevention outcome expectations on consumer behaviour. While promotion outcome expectation constructs proved non-significant, self-identity correlates with prevention outcome expectations. Research limitations/implications There are several limitations that the authors are aware of regarding this study. First of all, since the authors rely on self-reported measures, optimistic bias might have affected participants’ responses (Weinstein, 1980). Second, results may be influenced by the choice of the specific information provided to consumers for the analysis; different claims and different information framings should be tested (LeBoeuf and Shafir, 2003). Practical implications Implications stemming from the results encourage the promotion of omega-3 enriched mozzarella cheese based on stimulating outcome expectations, bearing in mind that individual motivations should be enhanced by self-identity beliefs. Originality/value Although the combined role of self-efficacy and outcome expectations on personal intention to adopt healthy behaviour has already been demonstrated (Keller, 2006; Tudoran et al., 2012), to the best of the knowledge no previous study relates individual behaviour to an intention measured as a WTP for an actual product. In addition, current study has applied a non-hypothetical BDM (from Becker et al., 1964) auction in-store experiment.

Background: Closed-loop agri-food supply chains have a high potential to reduce environmental and economic costs resulting from food waste disposal. This paper illustrates an alternative to the traditional supply chain of bread based on the principles of a circular economy. Methods: Six circular interactions among seven actors (grain farmers, bread producers, retailers, compostable packaging manufacturers, insect breeders, livestock farmers, consumers) of the circular filière are created in order to achieve the goal of "zero waste". In the model, two radical technological innovations are considered: insects used as animal feed and polylactic acid compostable packaging. Results: The main challenges for the implementation of the new supply chain are identified. Finally, some recent patents related to bread sustainable production, investigated in the current paper, are considered. Conclusion: Recommendations are given to academics and practitioners interested in the bio-based circular economy model approach for transforming agri-food supply chains. © 2016 Bentham Science Publishers.

Partial Retraction of: The EMBO Journal (2010) 29: 3607-3620. DOI: 10.1038/emboj.2010.237 | Published online 24 September 2010 Journal statement The journal contacted the authors in February 2022 about potential image insertions and duplications in Fig 4A and 4E. In the absence of source data, the authors are retracting Fig 4A, the lower panel of Fig 4E (LAMP1 immunoblot), and the following statements in the text that rely on these data: "Quantitative analysis showed that the percentage of Flotillin-1 associated with DRMs was increased in LSD endolysosomal membranes (Figure 4A), indicating an increased amount of cholesterol-enriched regions in these membrane samples." "LAMP1 also displayed a similar distribution profile in WT and LSD cells (Figure 4E)". Author statement The authors could not verify the aberrations in panel A of Fig 4 and the lower immunoblot (LAMP1) of 4E because the original source data are no longer available (12 years after publication, which is beyond the institute's 10-year data retention policy). The authors wish to clarify that the main conclusions of the paper are not affected by the retraction of Figure panels 4A and 4E for the following reasons: Figure panel 4A supports the observation that there are increased cholesterol-enhanced regions in LSD samples. This finding is also supported by data provided in figs 4B, 4C and 4D. Figure panel 4E: The LAMP1 blot in Fig 4E shows that the distribution of protein normally excluded from DRMs is not altered between Wt and LSD samples. This result is also supported by the upper blot in this panel (Transferrin receptor). The authors apologize for these errors and agree with this corrigendum; no response could be obtained from AL.

Sulfatases are enzymes that hydrolyse a diverse range of sulfate esters. Deficiency of lysosomal sulfatases leads to human diseases characterized by the accumulation of either GAGs (glycosaminoglycans) or sulfolipids. The catalytic activity of sulfatases resides in a unique formylglycine residue in their active site generated by the post-translational modification of a highly conserved cysteine residue. This modification is performed by SUMF1 (sulfatase-modifying factor 1), which is an essential factor for sulfatase activities. Mutations in the SUMF1 gene cause MSD (multiple sulfatase deficiency), an autosomal recessive disease in which the activities of all sulfatases are profoundly reduced. In previous studies, we have shown that SUMF1 has an enhancing effect on sulfatase activity when co-expressed with sulfatase genes in COS-7 cells. In the present study, we demonstrate that SUMF1 displays an enhancing effect on sulfatases activity when co-delivered with a sulfatase cDNA via AAV (adeno-associated virus) and LV (lentivirus) vectors in cells from individuals affected by five different diseases owing to sulfatase deficiencies or from murine models of the same diseases [i.e. MLD (metachromatic leukodystrophy), CDPX (X-linked dominant chondrodysplasia punctata) and MPS (mucopolysaccharidosis) II, IIIA and VI]. The SUMF1-enhancing effect on sulfatase activity resulted in an improved clearance of the intracellular GAG or sulfolipid accumulation. Moreover, we demonstrate that the SUMF1-enhancing effect is also present in vivo after AAV-mediated delivery of the sulfamidase gene to the muscle of MPSIIIA mice, resulting in a more efficient rescue of the phenotype. These results indicate that co-delivery of SUMF1 may enhance the efficacy of gene therapy in several sulfatase deficiencies.

In recent years a new form of food production and distribution organisation, as part of small-scale and local agriculture, has been gaining ground. Generically termed short supply chains (SSCs), this new model of food procurement comprises various forms such as community-supported agriculture, box schemes and solidarity purchase groups. Consumer participation in SSCs is dictated by deep motivations: while consumers are principally encouraged by the desire to preserve local producers, as well as the social and environmental aspects of farming, the attraction of SSCs is also tied to different and more complex ways of perceiving food quality. The quality issue in SSCs is not only seen in the light of classic attributes, such as taste and safety, but also in terms of social criteria built on the basis of aspects of products linked to social and environmental domains. This study provides an empirical assessment of consumers participating in SSCs to ascertain whether, and to what extent, those actively involved in an SSC show differences in terms of what is more personal and subjective, such as universal values and food-related lifestyles, compared with those who do not participate. In order to assess such relationships, data were collected from a solidarity purchase group in Sicily (southern Italy). For comparison, a group of consumers in conventional food outlets were also interviewed in the same city. Data were analysed with the propensity score matching method. Our results show that the decision to participate in a solidarity purchase group is especially dictated by profound ideological and emotional considerations. They emphasise the interest in preserving, protecting and sustaining the welfare of other people, in line with the fundamental purpose of short supply chains.

Depletion of natural resources has become a key issue on the European policy agenda. Bottom-up measures have emerged in several countries with a view to promoting awareness campaigns and environmental sustainability, with the agenda set by individuals who start up collective initiatives at the local level. Such collective action provides an incentive to free-ride on the contribution of others. Social norms and the consequent behavior of individuals involved in collective action assume a key role in ensuring sustainable use of a public good, achieving significant, long-lasting success. The present study aims to ascertain which determinants most affect farmers’ willingness to contribute to common resources. The empirical study was conducted in an area in the province of Avellino (southern Italy) most affected by soil erosion problems. The study focused on the willingness of farmers to contribute to the public good through biomass production (Giant Cane). In all, 175 face-to-face questionnaires were administered to farmers in September-November 2013. Schwartz’s norm-activation model variables were collected. A Tobit model was implemented in which the dependent variable was the land farmers stated they were willing to cultivate with Giant Cane. Four on five psychological constructs, based on the NAM, proved statistically significant with the expected sign, showing that an altruistic behavioral approach is useful to predict the individual’s decision to adopt cooperation norms.

Background: Impaired endothelial-dependent vasorelaxation (IEDV) precedes the development of cerebrovascular lesions in an experimental animal model of inherited stroke, the stroke-prone spontaneously hypertensive rat (SHRSP). We have previously shown that in this experimental model IEDV segregates in the SHRSP/stroke-resistant spontaneously hypertensive rat (SHR) F2 generation independently of blood pressure levels, thus suggesting the existence of a specific genetic basis for this trait.

Sulfatase modifying factor 1 (SUMF1) encodes for the formylglicine generating enzyme, which activates sulfatases by modifying a key cysteine residue within their catalytic domains. SUMF1 is mutated in patients affected by multiple sulfatase deficiency, a rare recessive disorder in which all sulfatase activities are impaired. Despite the absence of canonical retention/retrieval signals, SUMF1 is largely retained in the endoplasmic reticulum (ER), where it exerts its enzymatic activity on nascent sulfatases. Part of SUMF1 is secreted and paracrinally taken up by distant cells. Here we show that SUMF1 interacts with protein disulfide isomerase (PDI) and ERp44, two thioredoxin family members residing in the early secretory pathway, and with ERGIC-53, a lectin that shuttles between the ER and the Golgi. Functional assays reveal that these interactions are crucial for controlling SUMF1 traffic and function. PDI couples SUMF1 retention and activation in the ER. ERGIC-53 and ERp44 act downstream, favoring SUMF1 export from and retrieval to the ER, respectively. Silencing ERGIC-53 causes proteasomal degradation of SUMF1, while down-regulating ERp44 promotes its secretion. When over-expressed, each of three interactors favors intracellular accumulation. Our results reveal a multistep control of SUMF1 trafficking, with sequential interactions dynamically determining ER localization, activity and secretion.

Mucopolysaccharidosis type IIIA (MPS-IIIA or Sanfilippo syndrome) is a lysosomal storage disorder caused by the congenital deficiency of sulfamidase (SGSH) enzyme and consequent accumulation of partially degraded heparan sulfate (HS) in lysosomes. The central nervous system (CNS) is the predominant site of tissue damage in MPS-IIIA. Here we describe a gene therapy approach for MPS-IIIA in a mouse model using recombinant adeno-associated virus serotype 5 (AAV2/5) as a vehicle to deliver therapeutic genes to the CNS. SUMF1 (SUlfatase Modifying Factor 1) exhibits an enhancing effect on sulfatase activity when co-expressed with sulfatases. Consistent with these findings, we demonstrated that co-delivery of SUMF1 and SGSH (via an AAV2/5-CMV-SGSH-IRES-SUMF1 vector) resulted in a synergistic increase in SGSH activity, both in primary neural cells and in murine brain. A study aimed at testing the therapeutic efficacy of simultaneous brain administration of SUMF1 and SGSH was then performed by injecting the lateral ventricles of newborn MPS-IIIA/normal mice with either AAV2/5-CMV-SGSH-IRES-SUMF1 or AAV2/5-CMV-GFP vectors. Widespread GFP expression was observed within the GFP-injected brain, and a stable and significant increase of SGSH activity was detected in several brain regions following SGSH-IRES-SUMF1 administration. Treatment with AAV2/5-CMV-SGSH-IRES-SUMF1 vectors resulted in a visible reduction in lysosomal storage and inflammatory markers in transduced brain regions. Finally, the MPS-IIIA mice treated with therapeutic genes displayed an improvement in both motor and cognitive functions. Our results suggest that early treatment of CNS lesions by AAV-mediated intraventricular injection of both SGSH and SUMF1 genes may represent a feasible therapy for MPS-IIIA.

Sulfatases catalyze the hydrolysis of sulfate ester bonds from a wide variety of substrates and are implicated in several human inherited diseases. Multiple sulfatase deficiency (MSD) is a rare autosomal recessive disorder characterized by the simultaneous deficiency of all known sulfatases. MSD is caused by mutations in the Sulfatase Modifying Factor 1 (SUMF1) gene encoding the alpha-formylglycine generating enzyme (FGE), which is responsible for the post-translational modification of sulfatases. In all MSD patients, residual sulfatase activities are detectable, at variable levels. To correlate the nature of the residual sulfatase activities detected in MSD patients with residual FGE activity, four FGE mutants (i.e. p.S155P, p.R224W, p.R345C, p.R349W) found in homozygosis in MSD patients were analyzed. Using viral-mediated gene delivery, these mutants were over-expressed in mouse embryonic fibroblasts (MEFs) from a recently developed Sumf1 KO mouse line which is completely devoid of all sulfatase activities. The results obtained indicate that mutant SUMF1 cDNAs encode stable SUMF1 proteins which are of the appropriate molecular weight and are properly localized in the endoplasmic reticulum. Expression of these cDNAs in Sumf1-/- MEFs results in partial rescue of sulfatase activities. These data indicate that MSD is due to hypomorphic SUMF1 mutations and suggest that complete loss of SUMF1 function is likely to be lethal in humans.

Previous studies in a hypertensive animal model of stroke and in humans showed that mutations of the atrial natriuretic peptide (ANP) gene are associated with increased risk of stroke. To elucidate the vascular disease mechanisms that result from structural modifications of the ANP gene, we investigated a coding mutation of the ANP gene in stroke-prone spontaneously hypertensive rats (SHRsp). This mutation leads to a Gly/Ser transposition in the prosegment of ANP. We found that presence of this mutation is associated with increased immunostaining of ANP in the wall of SHRsp cerebral vessels. The mutation causes a major inhibitory effect on endothelial cell proliferation, as assessed by thymidine incorporation, and on angiogenesis, as determined by an endothelial cell tube formation assay, in human umbilical vein endothelial cells (HUVEC) exposed to ANP/SHRsp. These in vitro findings show that the SHRsp-derived form of ANP has an inhibitory effect on vascular remodeling and they provide further support for a role of the ANP gene in the pathogenesis of cerebrovascular disease in the animal model.

Background The main angiotensin (Ang) II subtype receptors (AT1R and AT2R) are involved in cellular growth processes and exert functionally antagonistic effects. Objective To characterize the mechanisms by which Ang II receptors influence growth, by investigating the interactions between Ang II subtype receptors and epidermal growth factor (EGF) receptors on mitogen-activated protein kinase (MAPK) pathway activation. Design and methods The experiments were performed using a mouse fibroblast cell line, NIH3T3, by transient co-transfection with rat AT1R or AT2R expression vectors, or both. Extracellular-signal-regulated kinase (ERK)1/2 phosphorylation was analysed by western blot and the ERK activity was evaluated using PathDetect, an in-vivo signal transduction pathway trans-reporting system. Selective Ang II receptor antagonists (losartan for AT1R and PD123319 for AT2R) were used to investigate the contributions of each receptor to the response observed. Results Our data show that, in this cellular model, both Ang II receptors phosphorylate ERK1/2. However, in the cells expressing AT1R, the EGF-induced MAPK pathway was enhanced in the presence of Ang II in a synergistic fashion. In contrast, a reduction of EGF-induced MAPK activation was observed in the cells expressing AT2R. In cells expressing both Ang II subtype receptors, Ang II promoted an enhancement of EGF-induced MAPK activation. However, in the presence of the AT1R antagonist, losartan, the effect of EGF was reduced. Conclusion These data indicate the existence of an opposite cross-talk of AT1R and AT2R with EGF receptors, and suggest a complex functional interaction between these pathways in the regulation of cellular growth processes.

Abstract —Through the genotype/phenotype cosegregation analysis of an F 2 intercross, from the crossbreeding of stroke-prone spontaneously hypertensive rats (SHRSP) and stroke-resistant spontaneously hypertensive rats (SHR), we previously identified a quantitative trait locus for stroke on rat chromosome 5 ( STR2 ) that colocalized with the genes encoding atrial and brain natriuretic peptides ( ANP and BNP ) and conferred a stroke-delaying effect. To further characterize ANP and BNP as candidates for stroke, we performed additional studies. Comparative sequence analysis revealed point mutations in both the coding and regulatory regions of ANP , whereas no interstrain differences were found for BNP . In in vitro studies in COS-7 and AtT-20 cells that were performed to test the relevance of a G→A substitution at position 1125, a Gly→Ser transposition in the SHRSP pro-ANP peptide resulted in different posttranslational processing of the SHRSP ANP gene product that was also associated with higher cGMP production ( P ANP demonstrated a significantly lower ANP promoter activation in endothelial cells (PANP ). In addition, the expression of ANP was significantly reduced in the brain, but not in the atria, of SHRSP compared with SHR ( P BNP expression. The present results reveal substantial differences in ANP , but not BNP , structure and product among SHR and SHRSP, which supports a role of ANP in the pathogenesis of stroke in the SHRSP animal model.

Objective To investigate whether angiotensin II type 2 (AT 2 ) receptor (AT 2 -r) promoter activity and expression are modulated by angiotensin II (Ang II), and whether the AT 1 receptor (AT 1 -r) is involved in this effect. Design and methods Primary endothelial cells obtained from neonatal rat aorta, expressing both receptors, were transfected with the rat AT 2 -r promoter region cloned into a pCAT-reporter vector. The reporter-expression study was performed in a transient transfection assay system. Transfected cells were studied following angiotensin-converting enzyme inhibition to prevent endogenous formation of Ang II. Cells were subsequently stimulated for 6 h with Ang II, either alone or in combination with the AT 1 -r antagonist DuP753. AT 2 -r mRNA was assessed by RNase protection assay during the same pharmacological stimuli. Results Stimulation with Ang II caused an increase in promoter activity (+50%, P< 0.05 versus baseline), whereas mRNA expression was reduced by 50% (P < 0.05 versus baseline). Concomitant treatment with DuP753 and Ang II was associated with a 98% increase in promoter activity (P< 0.05 versus baseline). DuP753 also prevented the reduction in mRNA; it actually produced a 100% increase in AT 2 -r mRNA accumulation (P< 0.01 versus baseline). Studies with the AT 2 -r antagonist PD123319 indicate that the AT 2 -r is also involved in the regulation of AT 2 -r gene promoter activity. Conclusions These data indicate that Ang II increases AT 2 -r promoter activity and decreases AT 2 -r mRNA accumulation in endothelial cells. The AT 1 subtype receptor is involved in the modulation of both effects of Ang II. These findings suggest that changes in the expression of AT 2 receptors may occur during treatment with AT 1 -r antagonists, and they indicate the existence of a cross-talk between AT 1 and AT 2 receptors.