28 research outputs found
Evolutionary perspective on mammalian inorganic polyphosphate (polyP) biology
Get PDFInorganic polyphosphate (polyP), the polymeric form of phosphate, is attracting ever-growing attention due to the many functions it appears to perform within mammalian cells. This essay does not aim to systematically review the copious mammalian polyP literature. Instead, we examined polyP synthesis and functions in various microorganisms and used an evolutionary perspective to theorise key issues of this field and propose solutions. By highlighting the presence of VTC4 in distinct species of very divergent eucaryote clades (Opisthokonta, Viridiplantae, Discoba, and the SAR), we propose that whilst polyP synthesising machinery was present in the ancestral eukaryote, most lineages subsequently lost it during evolution. The analysis of the bacteria-acquired amoeba PPK1 and its unique polyP physiology suggests that eukaryote cells must have developed mechanisms to limit cytosolic polyP accumulation. We reviewed the literature on polyP in the mitochondria from the perspective of its endosymbiotic origin from bacteria, highlighting how mitochondria could possess a polyP physiology reminiscent of their 'bacterial' beginning that is not yet investigated. Finally, we emphasised the similarities that the anionic polyP shares with the better-understood negatively charged polymers DNA and RNA, postulating that the nucleus offers an ideal environment where polyP physiology might thrive
Characterization of the metabolic profile of adipose tissue in spontaneously hypertensive rats and its involvement with the renin-angiotensin-aldosterone system
Get PDFOrientador: Dora Maria Grassi KassisseTese (doutorado) - Universidade Estadual de Campinas, Instituto de BiologiaResumo: A ativação crônica do eixo hipotálamo-hipófise-adrenal, do sistema nervoso simpático (SNS) e, consequentemente, do sistema renina-angiotensina-aldosterona (SRAA) tem papel crucial no desenvolvimento da hipertensão e de doenças metabólicas. Além de presente em diferentes tecidos, já foi comprovado que o adipócito produz todos os elementos do SRAA, envolvendo o eixo adipócito-corticomedular diretamente com a obesidade. O objetivo deste trabalho foi caracterizar o perfil metabólico do tecido adiposo em ratos espontaneamente hipertensos (SHR) e o seu envolvimento com o sistema renina-angiotensina-aldosterona. O peso corpóreo, ingestão alimentar e hídrica, coleta de sangue para análises séricas e de tecidos para morfometria e FLIM (Fluorescence-lifetime imaging microscopy) foram realizadas na 6ª e na 15ª semana de vida. Os ensaios funcionais foram realizados com adipócitos epididimais isolados de ratos submetidos a jejum prévio de 12-16h na 15ª semana de vida. Os SHR apresentaram valores menores no peso corporal e na glicemia de jejum, além de apresentarem uma taxa basal maior de produção de lactato por volume de adipócitos. A estimulação por angiotensina II (AII) e o bloqueio de seus receptores não interferiram na produção de lactato. A estimulação de noradrenalina e sua combinação com AII sugere uma modulação e/ou competição na cascata downstream para a troca do metabolismo glicolítico pelo lipolítico em todas as linhagens, demonstrando que a hipolipodristrofia exibida em SHR não é ocasionada por nenhum distúrbio nestas vias. Além disso, demonstramos que o fenômeno do whitening está associado com mudanças ocasionadas pela idade, podendo ser moduladas pelo eixo Hipotálamo-Hipófise-Tireóide (TRH-T3). Desta forma, o ambiente hormonal proporcionado pelo desenvolvimento da hipertensão pode destacar moléculas-chave que podem ser o caminho para o desenvolvimento de abordagens terapêuticas inovadoras para o tratamento de disfunções da adiposidade e hipertensão, além de esclarecer o entendimento sobre a relação causal entre hipolipodistrofia e hipertensãoAbstract: Chronic stress is associated with cardiovascular and metabolic disorders. The chronic activation of the hypothalamic-pituitary-adrenal axis, the sympathetic nervous system (SNS) and, consequently, the renin-angiotensin-aldosterone system (RAAS) plays a crucial role in the development of hypertension and metabolic diseases. It has been proven that the adipocyte produces all elements of the RAAS, involving the adipocyte-corticomedullary axis directly to obesity. The objective of this study was to characterize the metabolic profile of adipose tissue in spontaneously hypertensive rats (SHR) and its involvement with the renin-angiotensin-aldosterone system. Body weight, food and water intake, blood collection for serum and tissue analyzes for morphometry and FLIM (Fluorescence-lifetime imaging microscopy) were performed at the 6th and 15th week of life. Functional assays were performed with epididymal isolated adipocytes from rats submitted to a previous fast of 12-16h in the 15th week of life. The SHR presented lower values for body weight and fasting blood glucose, in addition to presenting a higher basal rate of lactate production per adipocyte volume. Angiotensin II (AII) stimulation and blockade of its receptors did not interfere with lactate production. Norepinephrine stimulation and its combination with AII suggests a modulation and/or competition in the downstream cascade for the exchange of glycolitic to lipolytic metabolism in all strains, demonstrating that the hypolodystrophy exhibited by SHR is not caused by any disturbance in these pathways. Moreover, we demonstrated that the whitening phenomenon is associated with changes caused by age and can be modulated by the Hypothalamic-Pituitary-Thyroid (TRH-T3) axis. Thus, the hormonal environment provided by the development of hypertension may highlight key molecules that may be the pathway for the development of novel and innovative therapeutic approaches for the treatment of adiposity dysfunctions and hypertension, in addition to clarify the understanding about the causal relationship between hypolipodystrophy and hypertensionDoutoradoFisiologiaDoutor em Biologia Funcional e MolecularCAPE
On the covalent nature of lysine polyphosphorylation
Get PDFPost-translational modifications of proteins (PTMs) introduce an extra layer of complexity to cellular regulation. Although phosphorylation of serine, threonine, and tyrosine residues is well-known as PTMs, lysine is, in fact, the most heavily modified amino acid, with over 30 types of PTMs on lysine having been characterized. One of the most recently discovered PTMs on lysine residues is polyphosphorylation, which sees linear chains of inorganic polyphosphates (polyP) attached to lysine residues. The labile nature of phosphoramidate bonds raises the question of whether this modification is covalent in nature. Here, we used buffers with very high ionic strength, which would disrupt any non-covalent interactions, and confirmed that lysine polyphosphorylation occurs covalently on proteins containing PASK domains (polyacidic, serine-, and lysine-rich), such as the budding yeast protein nuclear signal recognition 1 (Nsr1) and the mammalian protein nucleolin. This Matters Arising Response paper addresses the Neville et al. (2024) Matters Arising paper, published concurrently in Molecular Cell
The expanding role of Nogo-B in hypertension:linking kidney physiology, endothelial function and inflammation
Get PDFAlthough Nogo-B has been studied in neural development and vascular biology, its integrative role across renal, vascular and inflammatory pathways in hypertension has not yet been systematically reviewed. Here, we synthesize emerging evidence positioning Nogo-B as a central modulator of blood pressure control. Its expression in the aldosterone-sensitive distal nephron and vascular endothelium suggests a central role in electrolyte and fluid balance, as well as vascular physiology.</p
A new perspective of lactatogenesis by isolated adipocytes
No full textIncreased adipose tissue mass exhibited greater capacity of glucose transformation in lactate, highlighting lactatogenesis as a crucial factor in body size. Classically, lactate produced by isolated adipocytes are expressed per million of cells and were never correlated with their size. Spontaneously hypertensive rats (SHR) have a lower body weight and smaller adipocytes when compared to Wistar-Kyoto. We evaluated basal lactate by epididymal 15-weeks-old isolated adipocytes of SHR, Wistar-Kyoto and Wistar. Basal lactate was similar when expressed by one million cells. However, SHR adipocytes were smaller, so we adjusted the results by cell volume and SHR showed higher basal lactate production which was directly endorsed by hyperlactatemia in the presented conditions. Thereby, we suggest a new perspective on lactatogenesis analysis by adipocytes, which could be linked to the receptors density and associate enzymes. Moreover, we showed that the thin and hypertensive rats can be hyperlactemic in fasting conditions498CONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICO - CNPQCOORDENAÇÃO DE APERFEIÇOAMENTO DE PESSOAL DE NÍVEL SUPERIOR - CAPESFUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULO - FAPESPnão temnão tem2014/17538-6The study is part of a PhD thesis of Borghi, F. under Prof Dr Dora Maria Grassi Kassisse supervision. This study was supported by Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES), Serviço de Apoio ao Estudante da Unicamp (SAE), Fundo de Apoio ao Ensino, à Pesquisa e Extensão (Faepex-PRP), Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP – 2014/17538-6) and Programas de Iniciação Científica e Tecnológica da UNICAMP - Conselho Nacional de Desenvolvimento Científico e Tecnológico (PIBIC-CNPq/Brazil). We state there are no competing financial interests in the work describe
Psychosocial stress, depressive signs, resilience and coping strategies in students, professors and employees of the university of campinas (unicamp)
No full textA new mammalian model reveals inorganic polyphosphate channelling into the nucleolus induces a hyper-condensate state. by Filipy Borghi et al.
No full textRAW DATA PRESENTED IN THE FIGURE OF:A new mammalian model reveals inorganic polyphosphate channelling into the nucleolus induces a hyper-condensate state.Borghi, Filipy1; Azevedo, Cristina1; Johnson, Errin2; Burden, Jemima J.1; Saiardi, Adolfo1*.THIS DATASET IS ARCHIVED AT DANS/EASY, BUT NOT ACCESSIBLE HERE. TO VIEW A LIST OF FILES AND ACCESS THE FILES IN THIS DATASET CLICK ON THE DOI-LINK ABOV
The impact of confinement in the psychosocial behaviour due COVID-19 among members of a Brazilian university
Get PDFBACKGROUND: The current situation due COVID-19 may cause an eminent impact on mental health because the confinement restrictions. AIMS: The aim of this study was to analyze and compare perceived stress, resilience, depression symptoms and coping strategies on the members of University of Campinas, in Brazil, before and during the outbreak of the COVID-19. METHODS: Volunteers over 18 years of both sexes, members of the University of Campinas (Unicamp) in Brazil answered instruments related to perceived stress, depression, resilience and coping strategies during final exams at the end of semester during 2018 to 2020. RESULTS: We obtained 1,135 responses (893 before COVID-19 and 242 during COVID-19). The volunteers did not show significant differences for perceived stress, depressive signs and resilience before and during the pandemic. In both periods, men exhibited lower scores for perceived stress and depression and higher scores for resilience when compared to women. Undergraduate and graduate students exhibited higher perceived stress scores, more pronounced depressive signs and lower resilience, and employees and professors presented lower scores for perceived stress, depressive signs and greater resilience. CONCLUSIONS: These first months of confinement did not directly affect the scores of perceived stress, depression and resilience, however, each subgroup adapted to the new routine by changing the coping strategy used. This study suggests the importance of monitoring the mental health of member in the university, especially in times of epidemic, in the search for policies that aim to improve the resilience of the population and seek positive and effective coping strategies within the university environment
History of vascular reactivity models and their involvement in hypertension pathogenesis
No full text Abstract. Hypertension is a silent and multifactorial disease. Over two centuries ago, the first device to record blood pressure was developed, making it possible to determine normotension and to establish criteria for hypertension. Since then, several studies have contributed to advance knowledge in this area, promoting significant advances in pharmacological treatments and, as a result, increasing survival of hypertensive people. The main models developed for the study of hypertension and the main findings in the vascular area are included in this review. We considered aspects related to vascular reactivity, changes in the population, and action of beta adrenergic receptors in the pathogenesis of hypertension. </jats:p
Signaling downstream cascade crosstalk induced by noradrenaline on angiotensin II metabolic activity in adipocytes
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