22 research outputs found
A Model for Manganese interaction with Deinococcus radiodurans proteome network involved in ROS response and defense
No full textA complex network of regulatory proteins takes part in the mechanism underlying the radioresistance of Deinoccocus radiodurans bacterium (DR). The interaction of Mn(II) ions with DR-proteins and peptides seems to be responsible for proteins protection from oxidative damage induced by Reactive Oxygen Species during irradiation.
In the present work we describe a combined approach of bioinformatic strategies based on structural data and annotation to predict the Mn(II)-binding proteins encoded by the genome of DR and, in parallel, the same predictions for other bacteria were performed; the comparison revealed that, in most of the cases, the content of Mn(II)-binding proteins is significantly higher in radioresistant than in radiosensitive bacteria. Moreover, we report the in silico protein–protein interaction network of the putative Mn(II)-proteins, remodeled in order to enhance the knowledge about the impact of Mn-binding proteins in DR ability to protect also DNA from various damaging agents such as ionizing radiation, UV radiation and oxidative stress
Immunotoxicity of cocaine and crack
No full textThe toxicity of cocaine and crack was studied on the protozoan Tetrahymena pyriformis, using several endpoints, such as the DNA content of the macronuclei and the phagocytic ability. Both forms induced an increase in the DNA content of the protozoan, which indicates the stimulation of the mitotic process. In contrast, the phagocytic activity of the protozoan was decreased after the administration of cocaine, an effect that was more extensive after the administration of crack. These results, derived from previous experiments, suggest a possible relationship between the observed immunosuppression in cocaine abusers and the immunosuppression found in the protozoan. This suppression subsequently may play a role in the development of other opportunistic infections in drug abusers. This paper, based on in vivo experiments with the protozoan Tetrahymena, suggests the compromised immune response in cocaine addicts and assures the reported effects of cocaine on immune cell function. © 2011 Bentham Science Publishers Ltd
Zinc and human health: An update
No full textThe importance of micronutrients in health and nutrition is undisputable, and among them, zinc is an essential element whose significance to health is increasingly appreciated and whose deficiency may play an important role in the appearance of diseases. Zinc is one of the most important trace elements in the organism, with three major biological roles, as catalyst, structural, and regulatory ion. Zinc-binding motifs are found in many proteins encoded by the human genome physiologically, and free zinc is mainly regulated at the single-cell level. Zinc has critical effect in homeostasis, in immune function, in oxidative stress, in apoptosis, and in aging, and significant disorders of great public health interest are associated with zinc deficiency. In many chronic diseases, including atherosclerosis, several malignancies, neurological disorders, autoimmune diseases, aging, age-related degenerative diseases, and Wilson's disease, the concurrent zinc deficiency may complicate the clinical features, affect adversely immunological status, increase oxidative stress, and lead to the generation of inflammatory cytokines. In these diseases, oxidative stress and chronic inflammation may play important causative roles. It is therefore important that status of zinc is assessed in any case and zinc deficiency is corrected, since the unique properties of zinc may have significant therapeutic benefits in these diseases. In the present paper, we review the zinc as a multipurpose trace element, its biological role in homeostasis, proliferation and apoptosis and its role in immunity and in chronic diseases, such as cancer, diabetes, depression, Wilson's disease, Alzheimer's disease, and other age-related diseases. © Springer-Verlag 2011
Recent aspects of the effects of zinc on human health
No full textZinc (Zn) is one of the most important essential nutrients of great public health significance. It is involved in numerous biological functions and it is considered as a multipurpose trace element, due to its capacity to bind to more than 300 enzymes and more than 2000 transcriptional factors. Its role in biochemical pathways and cellular functions, such as the response to oxidative stress, homeostasis, immune responses, DNA replication, DNA damage repair, cell cycle progression, apoptosis and aging is significant. Zn is required for the synthesis of protein and collagen, thus contributing to wound healing and a healthy skin. Metallothioneins are metal-binding proteins and they are potent scavengers of heavy metals, including Zn, and protect the organism against stress. Zn deficiency is observed almost in 17% of the global population and affects many organ systems, leading to dysfunction of both humoral and cell-mediated immunity, thus increasing the susceptibility to infection. This review gives a thorough insight into the most recent evidence on the association between Zn biochemistry and human pathologies, epigenetic processes, gut microbial composition, drug targets and nanomedicine. © 2020, Springer-Verlag GmbH Germany, part of Springer Nature
Il ruolo del Mn(II) nel meccanismo di radioresistenza del batterio Deinococcus radiodurans
No full textIl Deinoccocus radiodurans (Dr) è un batterio che fin dal giorno della sua scoperta è apparso essere uno dei microrganismi più radioresistenti, in grado di sopportare dosi di radiazioni superiori anche a 10 KGy, dose circa 3000 volte superiore a quella letale per l’uomo.
La comprensione dei meccanismi molecolari che stanno alla base della radioprotezione può aprire la strada a molteplici potenziali applicazioni: dal campo della medicina e della biotecnologia, a quello ambientale.
Il meccanismo di difesa del Dr, sebbene non completamente compreso, sembra coinvolgere l’interazione dello ione Mn(II) con enzimi ROS-scavenging e la formazione di complessi ROS-scavenging tra lo ione metallico e piccole o medie molecole quali carotenoidi, amminoacidi, peptidi e gruppi fosfato, la cui azione è risultata essere cruciale per la protezione delle proteine dal danno ossidativo causato dall'irradiazione e, di conseguenza, per la sopravvivenza del batterio.
La presentazione si concentrerà sul ruolo dei complessi del Mn(II) con peptidi e proteine nel meccanismo di radioresistenza del Dr, con un approccio basato su tecniche potenziometriche, spettroscopiche (NMR, EPR, UV-Vis, CD), spettrometriche (ESI-MS) e in silico quali strategie bioinformatiche combinate: Retrieval of Domains and Genome Browsing [1,3].
Riferimenti:
[1] M. Peana, C.T. Chasapis, G. Simula, S. Medici, M.A. Zoroddu, A Model for Manganese interaction with Deinococcus radiodurans proteome network involved in ROS response and defense, J Trace Elem Med Biol 50 (2018) 465-473.
[2] M. Peana, S. Medici, H.A. Pangburn, T.J. Lamkin, M. Ostrowska, E. Gumienna-Kontecka, M.A. Zoroddu, Manganese binding to antioxidant peptides involved in extreme radiation resistance in Deinococcus radiodurans, J Inorg Biochem 164 (2016) 49-58.
[3] M. Peana, S. Medici, M. Ostrowska, E. Gumienna-Kontecka, M.A. Zoroddu, Interaction of Mn(II) and Cu(II) with antioxidant peptides derived from the extremophile bacterium Deinococcus Radiodurans, in preparation
Novel Approaches in the Immunotherapy of Multiple Sclerosis: Cyclization of Myelin Epitope Peptides and Conjugation with Mannan
No full textMultiple Sclerosis (MS) is a serious autoimmune disease. The patient in an advanced state of the disease has restrained mobility and remains handicapped. It is therefore understandable that there is a great need for novel drugs and vaccines for the treatment of MS. Herein we summarise two major approaches applied for the treatment of the disease using peptide molecules alone or conjugated with mannan. The first approach focuses on selective myelin epitope peptide or peptide mimetic therapy alone or conjugated with mannan, and the second on immune-therapy by preventing or controlling disease through the release of appropriate cytokines. In both approaches the use of cyclic peptides offers the advantage of increased stability from proteolytic enzymes. In these approaches, the synthesis of myelin epitope peptides conjugated to mannan is of particular interest as this was found to protect mice against experimental autoimmune encephalomyelitis, an animal model of MS, in prophylactic and therapeutic protocols. Protection was peptide-specific and associated with reduced antigen-specific T cell proliferation. The aim of the studies of these peptide epitope analogs is to understand their molecular basis of interactions with human autoimmune T-cell receptor and a MS-associated human leucocyte antigen (HLA)-DR2b. This knowledge will lead the rational design to new beneficial non-peptide mimetic analogs for the treatment of MS. Some issues of the use of nanotechnology will also be addressed as a future trend to tackle the disease. We highlight novel immunomodulation and vaccine-based research against MS based on myelin epitope peptides and strategies developed in our laboratories. © 2021 by the authors. Licensee MDPI, Basel, Switzerland
Identification of the zinc, copper and cadmium metalloproteome of the protozoon Tetrahymena thermophila by systematic bioinformatics
No full textTetrahymena thermophila (T. thermophila) is a ciliated protozoon that can detect freshwater pollution by heavy metals (“whole-cell biosensor”). This work employed a systematic bioinformatics approach to predict and analyze the metalloproteome of T. thermophila for the essential Zn, Cu and the non-essential Cd. 3784 metal-binding proteins were identified compared to the 456 annotated so far in UniProt. The localization, functional classification, and the functionally enriched network of the newly identified metalloproteome are presented. Cd toxicity could be explained in terms of the metal replacing Cu and especially Zn in MAPKs, transporters and antioxidant enzymes. The predicted results for Cd toxicity and responses reflect those observed experimentally in different organisms after their exposure to Cd. © 2017, Springer-Verlag Berlin Heidelberg
Actions of Novel Angiotensin Receptor Blocking Drugs, Bisartans, Relevant for COVID-19 Therapy: Biased Agonism at Angiotensin Receptors and the Beneficial Effects of Neprilysin in the Renin Angiotensin System
No full textAngiotensin receptor blockers (ARBs) used in the treatment of hypertension and potentially in SARS-CoV-2 infection exhibit inverse agonist effects at angiotensin AR1 receptors, suggesting the receptor may have evolved to accommodate naturally occurring angiotensin ‘antipeptides’. Screening of the human genome has identified a peptide (EGVYVHPV) encoded by mRNA, complementary to that encoding ANG II itself, which is an inverse agonist. Thus, opposite strands of DNA encode peptides with opposite effects at AR1 receptors. Agonism and inverse agonism at AR1 receptors can be explained by a receptor ‘switching’ between an activated state invoking receptor dimerization/G protein coupling and an inverse agonist state mediated by an alternative/second messenger that is slow to reverse. Both receptor states appear to be driven by the formation of the ANG II charge-relay system involving TyrOH-His/imidazole-Carboxylate (analogous to serine proteases). In this system, tyrosinate species formed are essential for activating AT1 and AT2 receptors. ANGII is also known to bind to the zinc-coordinated metalloprotease angiotensin converting enzyme 2 (ACE2) used by the COVID-19 virus to enter cells. Here we report in silico results demonstrating the binding of a new class of anionic biphenyl-tetrazole sartans (‘Bisartans’) to the active site zinc atom of the endopeptidase Neprilysin (NEP) involved in regulating hypertension, by modulating humoral levels of beneficial vasoactive peptides in the RAS such as vasodilator angiotensin (1–7). In vivo and modeling evidence further suggest Bisartans can inhibit ANG II-induced pulmonary edema and may be useful in combatting SARS-CoV-2 infection by inhibiting ACE2-mediated viral entry to cells. © 2022 by the authors
