Since the first studies of betaine

Since the first studies of betaine aldehyde oxidation in rats [13], the participation of betaine in the detoxification of homocysteine has well described, considering the activity of other salbutamol sulfate as betaine homocysteine methyltransferase and methionine synthase. But, there is a lack of attention when it comes to betaine synthesis and regulation. In this work, we quantified the BADH mRNA, protein levels and enzyme activity, along with GB content in left ventricle during physiological cardiac hypertrophy induced by pregnancy, and their reversible process postpartum.
Materials and methods
Results
Discussion Previous studies describe the tissue distribution of the mRNA and enzyme activity of human aldehyde dehydrogenase E3 (ALDH9) [6], this isoenzyme was identified as a BADH enzyme [5]. The human BADH has a high identity (92%) with the γ-trimethylaminobutyraldehyde dehydrogenase from rat, which is involved in the carnitine and betaine biosynthesis [2]. Their results indicated that higher mRNA levels were present in the skeletal and heart muscle. However, the major activity levels were located in the liver tissue (6.3 ± 1.8 nmol/min/mg), and the heart muscle presented 4-fold lower activity values (1.5 ± 0.4 nmol/min/mg). In this sense, authors found some discrepancies with the mRNA expression and catalytic activity in the samples evaluated, excluding a possible decomposition of mRNA samples and suggest a translational regulation of the enzyme. Our results regarding enzyme activity correlate with those reported in heart tissue of human ALDH9 with activity values of 1.33 nmol/min/mg protein in samples from non-pregnant rats. However, the mRNA, protein levels and enzyme activity increase during late pregnancy, pointing out that BADH in Sprague-Dawley rats seems not to be translational regulated, and is needed for the GB synthesis. With the development of more technology in genomics and proteomics, the hypertension studies to understand the mechanisms involved in their regulation are increased exponentially. To date, hundreds of gene loci and proteins associated with multiple cardiovascular diseases have been described [10], [11], [12]. Yet, some of the studies are not replicable, and further specific investigations are necessary to confirm the proteins identified in massive screenings. Despite the characterization studies of the members of the ALDH family, to the best of our knowledge, the only investigation related to cardiac hypertrophy is from the aldehyde dehydrogenase 2. The ALDH2 is a mitochondrial enzyme implicated in the detoxification of reactive aldehydes as 4-hydroxynonenal (4-HNE) and involved in the second step of ethanol metabolism, therefore protecting from cardiovascular diseases and alcoholic cardiomyopathy. The hypertensive rats presented an increase in ALDH2 activity, improved the redox profile and had a better ventricular function [17], [18]. The up-regulation of the ALDH2 is associated with the cardioprotective effect of ethanol postconditioning [19], and activation reduces ischemic damage in rats avoiding cardiomyocyte apoptosis [20]. The increase in GB levels at late pregnancy and postpartum correlates with the role of GB as a cellular osmolyte and osmoprotectant, considering their significant role in the reduction in vascular risk factor through methyl groups donor for the remethylation of homocysteine [21]. Besides, GB participates as a precursor of glycine from dimethylglycine dehydrogenase and sarcosine dehydrogenase activity [22]. Also, recent studies demonstrate that glycine reduces the pressure overload induced in cardiac hypertrophy in Sprague-Dawley rats in a dose-dependent manner, describing glycine as a novel cardioprotector [23]. Moreover, the synthesis of GB reduces the accumulation of toxic aldehydes and therefore avoids glutathione depletion and oxidative stress development, as aldehyde accumulation is related to the progression of the chronic cardiovascular diseases [24].