Protective Effects of Amino Acids Against Gabexate Mesilate–Induced Cell Injury in Porcine Aorta Endothelial Cells

Abstract

Abstract. Gabexate mesilate (GM), a serine protease inhibitor, often causes severe vascular injury. We previously reported that GM induced necrotic cell death via injury of the cell membrane in porcine aorta endothelial cells (PAECs). In the present study, we investigated the protective effects of amino acids against this GM-induced cell injury in PAECs.-threonine, and L-isoleucine significantly inhibited the GM-induced decrease of cell viability. Gly showed the most potent effect among these amino acids. Gly, L-Cys, L-Glu, and L-Gln also inhibited the GM-induced increase in the number of necrotic cells stained by propidium iodide (PI). However, these amino acids had no effect on the GM-induced inhibition of trypsin activity. Strychnine, MK-801, or dichlorokynurenic acid did not affect the protective effect of Gly. Gly completely suppressed the GM-induced increase in PI uptake, which occurred immediately after exposure to GM. These findings suggest that Gly exerts protection against GM-induced cellular membrane injury, and several amino acids such as Gly may be useful for prophylaxis of the GM-induced severe vascular injury.

Glycine transporter GLYT1 is essential for glycine-mediated protection of human intestinal epithelial cells against oxidative damage

“…Evidence of GlyR‐independent mechanisms of glycine cytoprotection has also been found in other tissues. High concentrations of glycine (10–30 m m compared with 1–5 m m used here) protected lung endothelial cells against gabexate mesilate‐induced injury and appeared to work by blocking the opening of membrane channels and pores in a glycine receptor‐independent mechanism (Aki et al 2008). Cytoprotection of liver cells by glycine has been observed in the absence of chloride and calcium ions (Frank et al 2000) in an as yet unexplained process.…”

Serum Metabolomic Profiling of All-Cause Mortality: A Prospective Analysis in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC) Study Cohort

“…Histidine may be independently inversely associated with age (51), and it can be metabolized to carnosine, a known antioxidant characterized as an "anti-aging" biochemical based on suppression of oxidative damage, glycation of proteins, and scavenging toxic age-related molecules (52). Glycine is the precursor of several molecular species, including purines and glutathione, and a substantial body of evidence supports its beneficial role in cytoprotection, antioxidation, antiinflammation responses, and metabolic regulation (53)(54)(55)(56)(57). Increased CVD mortality was also related to elevated serum mannose, consistent with findings from the Atherosclerosis Risk in Communities study (3), as well as to lysolipids (e.g., 1-linoleoyl-glycerophosphoethanolamine), which are considered important cell-signaling molecules that contribute to regulation of cell differentiation, growth, proliferation, and invasion (58)(59)(60)(61)(62), and to steroid hormones in the androgen pathway (e.g., 4-androsten-3β,17β-diol disulfate 1).…”