scholarly journals The Role of Mitochondria-Derived Peptides in Cardiovascular Diseases and Their Potential as Therapeutic Targets

2021 ◽  
Vol 22 (16) ◽  
pp. 8770
Author(s):  
Siarhei A. Dabravolski ◽  
Nikita G. Nikiforov ◽  
Antonina V. Starodubova ◽  
Tatyana V. Popkova ◽  
Alexander N. Orekhov

Mitochondria-derived peptides (MDPs) are small peptides hidden in the mitochondrial DNA, maintaining mitochondrial function and protecting cells under different stresses. Currently, three types of MDPs have been identified: Humanin, MOTS-c and SHLP1-6. MDPs have demonstrated anti-apoptotic and anti-inflammatory activities, reactive oxygen species and oxidative stress-protecting properties both in vitro and in vivo. Recent research suggests that MDPs have a significant cardioprotective role, affecting CVDs (cardiovascular diseases) development and progression. CVDs are the leading cause of death globally; this term combines disorders of the blood vessels and heart. In this review, we focus on the recent progress in understanding the relationships between MDPs and the main cardiovascular risk factors (atherosclerosis, insulin resistance, hyperlipidaemia and ageing). We also will discuss the therapeutic application of MDPs, modified and synthetic MDPs, and their potential as novel biomarkers and therapeutic targets.

Biomedicines ◽  
2021 ◽  
Vol 9 (4) ◽  
pp. 376
Author(s):  
Chantal B. Lucini ◽  
Ralf J. Braun

In the last decade, pieces of evidence for TDP-43-mediated mitochondrial dysfunction in neurodegenerative diseases have accumulated. In patient samples, in vitro and in vivo models have shown mitochondrial accumulation of TDP-43, concomitantly with hallmarks of mitochondrial destabilization, such as increased production of reactive oxygen species (ROS), reduced level of oxidative phosphorylation (OXPHOS), and mitochondrial membrane permeabilization. Incidences of TDP-43-dependent cell death, which depends on mitochondrial DNA (mtDNA) content, is increased upon ageing. However, the molecular pathways behind mitochondrion-dependent cell death in TDP-43 proteinopathies remained unclear. In this review, we discuss the role of TDP-43 in mitochondria, as well as in mitochondrion-dependent cell death. This review includes the recent discovery of the TDP-43-dependent activation of the innate immunity cyclic GMP-AMP synthase/stimulator of interferon genes (cGAS/STING) pathway. Unravelling cell death mechanisms upon TDP-43 accumulation in mitochondria may open up new opportunities in TDP-43 proteinopathy research.


2021 ◽  
Vol 22 (16) ◽  
pp. 8393
Author(s):  
Valentina Alfieri ◽  
Veronika A. Myasoedova ◽  
Maria Cristina Vinci ◽  
Maurizio Rondinelli ◽  
Paola Songia ◽  
...  

Diabetes mellitus (DM) is one of the most common and costly disorders that affect humans around the world. Recently, clinicians and scientists have focused their studies on the effects of glycemic variability (GV), which is especially associated with cardiovascular diseases. In healthy subjects, glycemia is a very stable parameter, while in poorly controlled DM patients, it oscillates greatly throughout the day and between days. Clinically, GV could be measured by different parameters, but there are no guidelines on standardized assessment. Nonetheless, DM patients with high GV experience worse cardiovascular disease outcomes. In vitro and in vivo studies showed that high GV causes several detrimental effects, such as increased oxidative stress, inflammation, and apoptosis linked to endothelial dysfunction. However, the evidence that treating GV is beneficial is still scanty. Clinical trials aiming to improve the diagnostic and prognostic accuracy of GV measurements correlated with cardiovascular outcomes are needed. The present review aims to evaluate the clinical link between high GV and cardiovascular diseases, taking into account the underlined biological mechanisms. A clear view of this challenge may be useful to standardize the clinical evaluation and to better identify treatments and strategies to counteract this DM aspect.


1984 ◽  
Vol 39 (9) ◽  
pp. 1276-1280 ◽  
Author(s):  
R. Baumann ◽  
M. Herrmann ◽  
H. Parlar

Dimerizations and reactions with water of pyrimidine bases are the primary steps held respon­sible for the deformation of DNA at short wavelengths in vitro and in vivo experiments. However the influence of oxygen in combination with water on the UV deformation at wavelengths rep­resentative for troposphere is evident from the observed data and both together are needed to change the DNA structure. The only plausible explanation for the effect of oxygen is the forma­tion of reactive oxygen species during the UV irradiation of DNA. In the present work the deformation of DNA by different oxygen species like singlet oxygen (1O2), superoxideanion (O2-), hydroxyradical (·OH), ozone (O3) and hydrogenperoxide (H2O2) is excluded with the help of chemical-trapping experiments. The photo-induced transformation proceeds via excited states of DNA. which react with groundstate oxygen to afford peroxide.


2019 ◽  
Vol 2019 ◽  
pp. 1-9 ◽  
Author(s):  
Shuang Li ◽  
Shilin Li ◽  
Shaobo Wu ◽  
Limin Chen

Although current diagnosis and treatment of hepatitis B virus (HBV) infection can maintain viral suppression, new therapies need to be invented to sustain off-treatment virologic suppression and reduce side effects. Exosomes act as intercellular communicators to facilitate direct transfer of proteins, lipids, and nucleic acids between cells in vitro and in vivo. Pioneering work has demonstrated that exosomal cargos changed markedly during HBV infection. An improved understanding of the functions of exosomes during HBV infection could lead to a powerful new strategy for preventing and treating HBV. In this review, we point out the role of exosomes in HBV infection: (1) exosomes could directly participate in HBV replication; (2) exosomes modulate immune response during HBV infections; (3) exosomal RNAs and proteins might be selected as novel biomarkers for the diagnosis of HBV infections; and (4) exosomes can also be designed as vaccines.


2012 ◽  
Vol 2012 ◽  
pp. 1-8 ◽  
Author(s):  
Vanessa Palermo ◽  
Fulvio Mattivi ◽  
Romano Silvestri ◽  
Giuseppe La Regina ◽  
Claudio Falcone ◽  
...  

In recent years, epidemiological and biochemical studies have shown that eating apples is associated with reduction of occurrence of cancer, degenerative, and cardiovascular diseases. This association is often attributed to the presence of antioxidants such as ascorbic acid (vitamin C) and polyphenols. The substances that hinder the presence of free radicals are also able to protect cells from aging. In our laboratory we used yeast, a unicellular eukaryotic organism, to determinein vivoefficacy of entire apples and their components, such as flesh, skin and polyphenolic fraction, to influence aging and oxidative stress. Our results indicate that all the apple components increase lifespan, with the best result given by the whole fruit, indicating a cooperative role of all apple components.


2015 ◽  
Vol 6 (9) ◽  
pp. 2890-2917 ◽  
Author(s):  
Cristian Del Bo’ ◽  
Daniela Martini ◽  
Marisa Porrini ◽  
Dorothy Klimis-Zacas ◽  
Patrizia Riso

Severalin vitroandin vivostudies have demonstrated that polyphenol-rich berries may counteract oxidative stress. In this review, we summarized the main finding from human intervention trials on the role of berries in the modulation of markers of oxidative lipid, protein and DNA damage.


Author(s):  
C A Le Guen ◽  
A F Jones ◽  
A H Barnett ◽  
J Lunec

Fluorescence (excitation 360 nm, emission 454 nm) generation in glycated albumin was investigated. Antioxidants and the metal chelator desferrioxamine (DFX) were used to study the mechanism of fluorescence generation. Delipidation studies, reverse phase chromatography and scanning fluorimetry were performed to examine the nature of this fluorescence. The mechanism of action of aminoguanidine, a compound which has been shown to inhibit the formation of visible fluorescence in proteins in vitro and in vivo was investigated in relation to glycation and by comparison with compounds with structural similarities. We conclude that hydrogen peroxide, metal ions and hydroxyl radicals are involved in fluorescence generation in glycated albumin, which is largely lipid in nature, and arises through glycation, amino acid oxidation and changes in bound lipid. Our results suggest that the action of aminoguanidine is not specifically related to blocking of ketoamine groups on glycated proteins as previously suggested.


Cells ◽  
2020 ◽  
Vol 9 (9) ◽  
pp. 1932
Author(s):  
Chiara D’Angelo ◽  
Sara Franceschelli ◽  
José Luis Quiles ◽  
Lorenza Speranza

The growing incidence of cardiovascular disease (CVD) has promoted investigations of natural molecules that could prevent and treat CVD. Among these, hydroxytyrosol, a polyphenolic compound of olive oil, is well known for its antioxidant, anti-inflammatory, and anti-atherogenic effects. Its strong antioxidant properties are due to the scavenging of radicals and the stimulation of synthesis and activity of antioxidant enzymes (SOD, CAT, HO-1, NOS, COX-2, GSH), which also limit the lipid peroxidation of low-density lipoprotein (LDL) cholesterol, a hallmark of atherosclerosis. Lowered inflammation and oxidative stress and an improved lipid profile were also demonstrated in healthy subjects as well as in metabolic syndrome patients after hydroxytyrosol (HT) supplementation. These results might open a new therapeutic scenario through personalized supplementation of HT in CVDs. This review is the first attempt to collect together scientific literature on HT in both in vitro and in vivo models, as well as in human clinical studies, describing its potential biological effects for cardiovascular health.


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