id	author	title	date	pages	extension	mime	words	sentences	flesch	summary	cache	txt
cord-103496-8tq78p2z	Wang, Ting	RAC1 nitration at Y32 IS involved in the endothelial barrier disruption associated with lipopolysaccharide-mediated acute lung injury	2020-11-13		.txt	text/plain	5855	302	45	title: RAC1 nitration at Y32 IS involved in the endothelial barrier disruption associated with lipopolysaccharide-mediated acute lung injury Using a molecular modeling approach, we designed a nitration shielding peptide for Rac1, designated NipR2 (nitration inhibitor peptide for the Rho GTPases 2), which attenuated the LPS-induced nitration of Rac1 at Y32, preserves Rac1 activity and attenuates the LPS-mediated disruption of the endothelial barrier in human lung microvascular endothelial cells (HLMVEC). Using a murine model of ALI induced by intratracheal installation of LPS we found that NipR2 successfully prevented Rac1 nitration and Rac1 inhibition, and more importantly attenuated pulmonary inflammation, reduced lung injury and prevented the loss of lung function. We anticipate that a successful clinical efficacy of NipR2 or similar product might require: 1) precision medicine approach to identify patients in the sub-group with satisfactory responsiveness of Rac1 nitration blockade, as not all triggers of ALI (e.g., trauma) will lead to endothelial oxidative stress and peroxynitrite generation; 2) combination therapy with other effective reagents, including suppressor of the cytokine storm and/or neutrophil eliminators; 3)	./cache/cord-103496-8tq78p2z.txt	./txt/cord-103496-8tq78p2z.txt