Publications by authors named "Anderson Kenedy Santos"

7 Publications

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Peptide fragments of bradykinin show unexpected biological activity not mediated by B or B receptors.

Br J Pharmacol 2022 Jun 9;179(12):3061-3077. Epub 2022 Feb 9.

Department of Physiology and Biophysics, Federal University of Minas Gerais, Belo Horizonte, Brazil.

Background And Purpose: Bradykinin (BK-(1-9)) is an endogenous nonapeptide involved in multiple physiological and pathological processes. Peptide fragments of bradykinin are believed to be biologically inactive. We have now tested the two major peptide fragments of bradykinin in human and animals.

Experimental Approach: BK peptides were quantified by MS in male rats. NO release was quantified from human, mouse and rat cells loaded with DAF-FM. Rat aortic rings were used to measure vascular reactivity. Changes in BP and HR were measured in conscious male rats. To evaluate pro-inflammatory effects both vascular permeability and nociception were measured in adult mice.

Key Results: BK-(1-7) and BK-(1-5) are produced in vivo from BK-(1-9). Both peptides induced NO production in all cell types tested. However, unlike BK-(1-9), NO production elicited by BK-(1-7) or BK-(1-5) was not inhibited by B or B receptor antagonists. BK-(1-7) and BK-(1-5) induced concentration-dependent vasorelaxation of aortic rings, without involvement of B or B receptors. Intravenous or intra-arterial administration of BK-(1-7) or BK-(1-5) induced similar hypotensive response in vivo. Nociceptive responses of BK-(1-7) and BK-(1-5) were reduced compared to BK-(1-9), and no increase in vascular permeability was observed for BK-(1-9) fragments.

Conclusions And Implications: BK-(1-7) and BK-(1-5) are endogenous peptides present in plasma. BK-related peptide fragments show biological activity, not mediated by B or B receptors. These BK fragments could constitute new, active components of the kallikrein-kinin system.
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http://dx.doi.org/10.1111/bph.15790DOI Listing
June 2022

GATA-1 mutation alters the spermatogonial phase and steroidogenesis in adult mouse testis.

Mol Cell Endocrinol 2022 02 26;542:111519. Epub 2021 Nov 26.

Laboratory of Cellular Biology, Department of Morphology, Institute of Biological Sciences, Federal University of Minas Gerais, Belo Horizonte, MG, Brazil. Electronic address:

GATA-1 is a transcription factor from the GATA family, which features zinc fingers for DNA binding. This protein was initially identified as a crucial regulator of blood cell differentiation, but it is currently known that the Gata-1 gene expression is not limited to this system. Although the testis is also a site of significant GATA-1 expression, its role in testicular cells remains considerably unexplored. In the present study, we evaluated the testicular morphophysiology of adult ΔdblGATA mice with a mutation in the GATA-1 protein. Regarding testicular histology, GATA-1 mutant mice exhibited few changes in the seminiferous tubules, particularly in germ cells. A high proportion of differentiated spermatogonia, an increased number of apoptotic pre-leptotene spermatocytes (Caspase-3-positive), and a high frequency of sperm head defects were observed in ΔdblGATA mice. The main differences were observed in the intertubular compartment, as ΔdblGATA mice showed several morphofunctional changes in Leydig cells. Reduced volume, increased number and down-regulation of steroidogenic enzymes were observed in ΔdblGATA Leydig cells. Moreover, the mutant animal showed lower serum testosterone concentration and high LH levels. These results are consistent with the phenotypic and biometric data of mutant mice, i.e., shorter anogenital index and reduced accessory sexual gland weight. In conclusion, our findings suggest that GATA-1 protein is an important factor for germ cell differentiation as well as for the steroidogenic activity in the testis.
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http://dx.doi.org/10.1016/j.mce.2021.111519DOI Listing
February 2022

Flow cytometry in the analysis of hematological parameters of tilapias: applications in environmental aquatic toxicology.

Environ Sci Pollut Res Int 2021 Feb 4;28(5):6242-6248. Epub 2021 Jan 4.

Department of Morphology, UFMG, Belo Horizonte, MG, Brazil.

Blood tissue has been used to assess animal health and the environment in which they live. This tissue is easily acquired and has the ability to respond to various adverse conditions. Several techniques have been employed in the detection of xenobiotic-induced cell damage in blood cells. In general, traditionally used technologies, such as cellular analysis in blood smears, are time-consuming and require great analytical capacity. The present study proposes flow cytometry as a method to detect changes in blood cell populations. Tilapia (Oreochromis niloticus) was selected as a model for plotting the profile of fish blood cell populations after exposure to xenobiotics without euthanizing animals or using cell markers. Populations of erythrocytes and lymphocytes were detected only by combining the techniques of FACSAria cell sorting and light microscopy. Systemic deleterious effects were found through blood analysis, such as an increased lymphocyte-rich population at 48 h of exposure followed by a subsequent decrease. Moreover, the time-dependent expression of Nrf2 suggests its participation in increased membrane disruption, indicating it has a central role in erythrocyte lifespan. The present results shed light on the viability of using flow cytometry for blood analysis of living fish.
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http://dx.doi.org/10.1007/s11356-020-12119-7DOI Listing
February 2021

An imaging flow cytometry-based technique to quantify erythrocyte nuclear alterations.

Aquat Toxicol 2020 Nov 28;228:105649. Epub 2020 Sep 28.

Department of Morphology, UFMG, Belo Horizonte, Minas Gerais, Brazil. Electronic address:

Morphological nuclear alterations are indicative of DNA damage and have been considered excellent markers of exposure to several pollutants in aquatic environments. Flow cytometry is a powerful technique for measuring cell phenotypes in large numbers of cells in a short period of time. This technique is suited to the study of cell populations and subset identification as a function of its high-throughput and multi-parameter characteristics. We used the quantification of erythrocyte nuclear alterations to compare the techniques of imaging flow cytometry and light microscopy. The comparison used blood samples of the fish Oreochromis niloticus assayed using cadmium as a nuclear alteration-inducing agent. The results showed that imaging flow cytometry has higher sensitivity than light microscopy for detecting and quantifying erythrocytic nuclear alterations. We conclude that imaging flow cytometry can produce fast and reliable results and could potentially be useful in studies involving fish erythrocytes under normal and impacted environmental conditions.
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http://dx.doi.org/10.1016/j.aquatox.2020.105649DOI Listing
November 2020

Alamandine enhances cardiomyocyte contractility in hypertensive rats through a nitric oxide-dependent activation of CaMKII.

Am J Physiol Cell Physiol 2020 04 8;318(4):C740-C750. Epub 2020 Jan 8.

Department of Physiology and Biophysics, Institute of Biological Sciences, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil.

Overstimulation of the renin-angiotensin system (RAS) has been implicated in the pathogenesis of various cardiovascular diseases. Alamandine is a peptide newly identified as a protective component of the RAS; however, the mechanisms involved in its beneficial effects remain elusive. By using a well-characterized rat model of hypertension, the TGR (mREN2)27, we show that mREN ventricular myocytes are prone to contractile enhancement mediated by short-term alamandine (100 nmol/L) stimulation of Mas-related G protein-coupled receptor member D (MrgD) receptors, while Sprague-Dawley control cells showed no effect. Additionally, alamandine prevents the Ca dysregulation classically exhibited by freshly isolated mREN myocytes. Accordingly, alamandine treatment of mREN myocytes attenuated Ca spark rate and enhanced Ca reuptake to the sarcoplasmic reticulum. Along with these findings, KN-93 fully inhibited the alamandine-induced increase in Ca transient magnitude and phospholamban (PLN) phosphorylation at Thr17, indicating CaMKII as a downstream effector of the MrgD signaling pathway. In mREN ventricular myocytes, alamandine treatment induced significant nitric oxide (NO) production. Importantly, NO synthase inhibition prevented the contractile actions of alamandine, including PLN-Thr17 phosphorylation at the CaMKII site, thereby indicating that NO acts upstream of CaMKII in the alamandine downstream signaling. Altogether, our results show that enhanced contractile responses mediated by alamandine in cardiomyocytes from hypertensive rats occur through a NO-dependent activation of CaMKII.
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http://dx.doi.org/10.1152/ajpcell.00153.2019DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7191420PMC
April 2020

Metabolic Disturbances Identified in Plasma Samples from ST-Segment Elevation Myocardial Infarction Patients.

Dis Markers 2019 1;2019:7676189. Epub 2019 Jul 1.

Departamento de Bioquímica e Imunologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil.

ST-segment elevation myocardial infarction (STEMI) is the most severe form of myocardial infarction (MI) and the main contributor to morbidity and mortality caused by MI worldwide. Frequently, STEMI is caused by complete and persistent occlusion of a coronary artery by a blood clot, which promotes heart damage. STEMI impairment triggers changes in gene transcription, protein expression, and metabolite concentrations, which grants a biosignature to the heart dysfunction. There is a major interest in identifying novel biomarkers that could improve the diagnosis of STEMI. In this study, the phenotypic characterization of STEMI patients ( = 15) and healthy individuals ( = 19) was performed, using a target metabolomics approach. Plasma samples were analyzed by UPLC-MS/MS (ultra-high-performance liquid chromatography-tandem mass spectrometry) and FIA-MS (MS-based flow injection analysis). The goal was to identify novel plasma biomarkers and metabolic signatures underlying STEMI. Concentrations of phosphatidylcholines, lysophosphatidylcholines, sphingomyelins, and biogenic amines were altered in STEMI patients in relation to healthy subjects. Also, after multivariate analysis, it was possible to identify alterations in the glycerophospholipids, alpha-linolenic acid, and sphingolipid metabolisms in STEMI patients.
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http://dx.doi.org/10.1155/2019/7676189DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6636502PMC
December 2019

Decoding resistant hypertension signalling pathways.

Clin Sci (Lond) 2017 Dec 28;131(23):2813-2834. Epub 2017 Nov 28.

Department of Biochemistry and Immunology, Institute of Biological Sciences, Universidade Federal de Minas Gerais, Av. Antôniol Carlos, 6627, Belo Horizonte 31270-901, MG, Brazil

Resistant hypertension (RH) is a clinical condition in which the hypertensive patient has become resistant to drug therapy and is often associated with increased cardiovascular morbidity and mortality. Several signalling pathways have been studied and related to the development and progression of RH: modulation of sympathetic activity by leptin and aldosterone, primary aldosteronism, arterial stiffness, endothelial dysfunction and variations in the renin-angiotensin-aldosterone system (RAAS). miRNAs comprise a family of small non-coding RNAs that participate in the regulation of gene expression at post-transcriptional level. miRNAs are involved in the development of both cardiovascular damage and hypertension. Little is known of the molecular mechanisms that lead to development and progression of this condition. This review aims to cover the potential roles of miRNAs in the mechanisms associated with the development and consequences of RH, and explore the current state of the art of diagnostic and therapeutic tools based on miRNA approaches.
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http://dx.doi.org/10.1042/CS20171398DOI Listing
December 2017
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