RESUMEN
Endogenous methylarginines, the catabolism products of proteins containing post-translationally methylated arginine residues, are the modulators of arginine metabolism. Endogenous methylarginines compete with arginine about cationic aminoacid transporter and some of them, e.g. asymmetric dimethylarginine (ADMA) and N-mono-methylarginine (MMA), are competitive inhibitors of nitric oxide synthases. The changes of arginine metabolism, induced by these methylarginines, may have serious consequences, because arginine is the precursor of cell-signalling molecules such as NO, agmatine, glutamate and gamma-aminobutyric acid (GABA) and the regulatory molecules polyamines. ADMA has also prooxidant properties and increases endothelial adhesiveness for monocytes. Asymmetric methyl-arginines induce endothelial dysfunction, which may be reversed by L-arginine supplementation, what is defined as "arginine paradox". The increased plasma concentration of asymmetric methylarginines is induced by hypercholesterolemic or hyperhomocysteinemic diets and by rich sodium chloride intake. The high level of plasma asymmetric methyl-arginines accompanies atherosclerosis, hypertension, chronic renal failure, diabetes, insulin resistence, hyperthyreosis, schizophrenia and sclerosis multiplex. The causes of increased concentration ADMA and MMA in these diseases are just now discovered. The hope in the future is the modulation of methylarginines concentration by regulation of expression and activities of enzymes taking part in the metabolism of these substances, particularly of dimethyl-arginine dimethyl-aminotransferase. The main aim of the present study is to pay attention to possibility of the modulation of asymmetric methyl-arginines concentration, what may be a new way of synthase nitric oxide activity regulation in vivo and may be useful in future therapy of patologies in which synthesis of NO is troubled.
Asunto(s)
Arginina/análogos & derivados , Enfermedades Cardiovasculares/metabolismo , Proteína-Arginina N-Metiltransferasas/metabolismo , Arginina/metabolismo , Enfermedades Cardiovasculares/etiología , Endotelio Vascular/metabolismo , Inhibidores Enzimáticos/metabolismo , HumanosRESUMEN
In chemical plant workers producing pesticides chronic bronchitis and disturbed pulmonary ventilation are frequent. The aim of the examination of the staff (sewage-treatment plant, waste combustion plant, waste storage, industrial water pumping station)--16 males aged 21-53 years--was to assess: 1. Connective tissue metabolism--serum concentration of type I and III procollagen propeptides, collagen I telopeptide, hydroxyproline, alpha1-AP and alpha2-M antiproteases, interstitial collagenase (MMP-1) activity, as well as urine hydroxyproline and desmosine. 2. Free radical damage--serum malonic dialdehyde (TBARS) and ceruloplasmin concentration, erythrocyte antioxidant enzymes activity (SOD, catalase, GPx, GR), and neutrophils myeloperoxidase reaction. 3. Humoral (serum IgG, A and M, C3 complement component and the circulating immune complexes) and cellular (percentage of CD3, CD4 and CD8 lymphocytes) immunity rates. As compared to controls the following changes were found: 1. decreased MMP-1 activity and increased alpha2-M serum concentration; 2. increased erythrocyte SOD and GPx activities; 3. decreased percentage of T lymphocytes (CD3), increased serum concentration of the C3 complement component and the circulating immune complexes. The results were compared with those in workers of the departments producing liquid pesticides, dust pesticides and chlorfenvinphose, the changes of the investigated parameters were found to be less expressed.