Abstract
Historically, proteolytic enzymes have been responsible for breaking peptide bonds between amino acids, catalyzing various reactions in metabolic pathways, and are important for maintaining and regulating these pathways. Recent studies have shown that the levels of various enzymes in the Renin-Angiotensin System (RAS), includingangiotensin-converting enzymes 1 and 2 (ACE and ACE2), neutral endopeptidase (NEP), chymase, renin, and cathepsin D, are altered in animal models subjected to fructose or glucose overloaded diets. Fructose metabolism leads to urate formation, which can cause tubular damage, inflammation, and hemodynamic changes. This study evaluated the modulation of peptide generation by classical and alternative RAS enzymes under the influence of fructose in immortalized human mesangial cells (MCs). Cells stimulated with 5mM and 30mM fructose showed decreased intracellular ACE activity and increased extracellular ACE activity, indicating the formation of Ang II. Increased intracellular Ang I result in increased renin and Cathepsin D activities, mediated by the stimulation of gene transcription enzymes. The activity of ACE2/NEP, responsible for the formation of Ang (1–7), counterbalances the actions of Ang II and protects against pathophysiological alterations caused by fructose. Intracellular chymase showed a higher expression than ACE, suggesting its involvement in the generation of increased intracellular Ang II, which may have an intracrine action. Fructose modulated the Ang II and Ang (1–7) axes in both intra-and extracellular compartments, demonstrating a balance between classical and alternative pathways and protecting MCs against matrix expansion and inflammation that contribute to glomerular sclerosis.