The aim of the present study was to assess age-dependent changes of proteins in the vastus lateralis muscle of physically active elderly and young subjects by a combination of two-dimensional difference gel electrophoresis, SDS-PAGE and ESI-MS/MS. The differences observed in the elderly group included down-regulation of regulatory myosin light chains, particularly the phosphorylated isoforms, a higher proportion of myosin heavy chain isoforms 1 and 2A, and enhanced oxidative and reduced glycolytic capacity.
Nitric oxide is becoming an increasingly important signalling molecule implicated in a growing number of physiological and pathophysiological processes. Moreover, with the recent advances in nitric oxide biochemistry, many well known drugs have been shown to act totally or partially by modulating NO metabolism with varying therapeutic results. The classic organic nitrates have been shown to exhibit beneficial therapeutic but suffer from some well known pitfalls (tolerability induction, abrupt cephalea and hypotension). Similarly, sydnonimines, another well known class of NO donor drugs, have a characteristically low therapeutic index (i.e., cyanide toxicity). At present, pharmacological researchers are designing and synthesising various chemical compounds capable of modulating NO metabolism for therapeutic purposes that also possess an optimal therapeutic index. Specifically, various new classes of NO donors are under intense pharmacological investigation (such as S-nitrosothiols, diazeniumdiolates, furoxans, zeolites and so on), each characterised by a particular pharmacokinetic and pharmacodynamic profile. To known the pharmacological development of these new NO donor drugs could help to ameliorate the use of these molecules in various therapeutic protocols. In fact, the pharmacologically modulated nitric oxide release showed to have an important therapeutic impact in the treatment of diseases such as arteriopathies, various acute and chronic inflammatory conditions, and several degenerative diseases. At present, the most important obstacle in the field of new NO donor drugs seems to be carefully targeting NO release to a particular tissue at an optimal concentration, so as to achieve a beneficial action and to limit possible toxic effects.
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