RESUMO
Oxidative (OS), reductive (RS), and nitrosative (NSS) stresses produce carbonylation, glycation, glutathionylation, sulfhydration, nitration, and nitrosylation reactions. OS, RS, and NSS are interrelated since RS results from an overactivation of antioxidant systems and NSS is the result of the overactivation of the oxidation of nitric oxide (NO). Here, we discuss the general characteristics of the three types of stress and the way by which the reactions they induce (a) damage the DNA structure causing strand breaks or inducing the formation of 8-oxo-d guanosine; (b) modify histones; (c) modify the activities of the enzymes that determine the establishment of epigenetic cues such as DNA methyl transferases, histone methyl transferases, acetyltransferases, and deacetylases; (d) alter DNA reparation enzymes by posttranslational mechanisms; and (e) regulate the activities of intracellular enzymes participating in metabolic reactions and in signaling pathways through posttranslational modifications. Furthermore, the three types of stress may establish new epigenetic marks through these reactions. The development of cardiometabolic disorders in adult life may be programed since early stages of development by epigenetic cues which may be established or modified by OS, RS, and NSS. Therefore, the three types of stress participate importantly in mediating the impact of the early life environment on later health and heritability. Here, we discuss their impact on cardiometabolic diseases. The epigenetic modifications induced by these stresses depend on union and release of chemical residues on a DNA sequence and/or on amino acid residues in proteins, and therefore, they are reversible and potentially treatable.
Assuntos
Doenças Cardiovasculares/enzimologia , Doenças Cardiovasculares/genética , Doenças Metabólicas/enzimologia , Doenças Metabólicas/genética , Estresse Nitrosativo/fisiologia , Estresse Oxidativo/fisiologia , Processamento de Proteína Pós-Traducional , Animais , Doenças Cardiovasculares/metabolismo , Doenças Cardiovasculares/patologia , Epigênese Genética , Humanos , Doenças Metabólicas/metabolismo , Doenças Metabólicas/patologia , Transdução de SinaisRESUMO
Prevalence of metabolic syndrome and progression of nephropathy depend on sex. We examined a protective effect of estradiol against nephropathy in metabolic syndrome through the modulation of the arachidonic acid metabolism by activating the 5-lipoxygenase and cytochrome p450 4A pathways. 28 female Wistar rats were divided into four groups of seven animals each: control, intact metabolic syndrome, ovariectomized metabolic syndrome, and metabolic syndrome ovariectomized plus estradiol. Blood pressure, body weight, body fat, triglycerides, insulin, HOMA-index, albuminuria, and TNF-α were increased in ovariectomized metabolic syndrome rats (p < 0.001). The perfusion pressure in isolated kidneys of ovariectomized metabolic syndrome rats in presence of 4 µg of arachidonic acid was increased. The inhibitors of the arachidonic acid metabolism Baicalein, Miconazole, and Indomethacin in these rats decreased the perfusion pressure by 57.62%, 99.83%, and 108.5%, respectively and they decreased creatinine clearance and the arachidonic acid percentage. Phospholipase A2 expression in the kidney of ovariectomized metabolic syndrome rats was not modified. 5-lipoxygenase was increased in metabolic syndrome ovariectomized rats while cytochrome p450 4A was decreased. In conclusion, the loss of estradiol increases renal damage while the treatment with estradiol benefits renal function by modulating arachidonic acid metabolism through the 5-lipoxygenase and cytochrome p450 4A pathways.
RESUMO
Renin-Angiotensin System (RAS) plays an important role in the development of Metabolic Syndrome (MS) and in aging. Angiotensin 1-7 (Ang 1-7) has opposite effects to Ang II. All of the components of RAS are expressed locally in adipose tissue and there is over-activation of adipose RAS in obesity and hypertension. We determined serum and abdominal adipose tissue Ang II and Ang 1-7 in control and MS rats during aging and the expression of AT1, AT2 and Mas in white adipose tissue. MS was induced by sucrose ingestion during 6, 12 and 18 months. During aging, an increase in body weight, abdominal fat and dyslipidemia were found but increases in aging MS rats were higher. Control and MS concentrations of serum Ang II from 6-month old rats were similar. Aging did not modify Ang II seric concentration in control rats but decreased it in MS rats. Ang II levels increased in WAT from both groups of rats. Serum and adipose tissue Ang 1-7 increased during aging in MS rats. Western blot analysis revealed that AT1 expression increased in the control group during aging while AT2 and Mas remained unchanged. In MS rats, AT1 and AT2 expression decreased significantly in aged rats. The high concentration of Ang 1-7 and adiponectin in old MS rats might be associated to an increased expression of PPAR-γ. PPAR-γ was increased in adipose tissue from MS rats. It decreased with aging in control rats and showed no changes during aging in MS rats. Ang 1-7/Mas axis was the predominant pathway in WAT from old MS animals and could represent a potential target for therapeutical strategies in the treatment of MS during aging.