biostudies-literatureUnknown58Yin YLNational Natural Science Foundation of China<h4>Background</h4>s: Hyperhomocysteinemia (HHcy) is one of risk factors for vascular cognitive impairment (VCI). GTP cyclohydrolase 1 (GCH1) deficiency is critical to oxidative stress in vascular dysfunction. The aim of this study was designed to examine whether HHcy induces VCI through GCH1 S-nitrosylation, a redox-related post-translational modification of cysteine.<h4>Methods</h4>The VCI model was induced by feeding mice homocysteine thiolactone (HTL) for 16 consecutive weeks. The cognitive functions were evaluated by step-down avoidance test, passive avoidance step-through task test, and Morris water maze (MWM) test. Protein S-nitrosylation was assayed using a biotin-switch method.<h4>Results</h4>In cell-free system, nitric oxide (NO) donor induced GCH1 protein S-nitrosylation and decRedox biology102540https://www.ebi.ac.uk/biostudies/studies/S-EPMC9673109biostudies-literatureNitrosative stress induced by homocysteine thiolactone drives vascular cognitive impairments via GTP cyclohydrolase 1 S-nitrosylation in vivo.PMC9673109Lu JXWang SXLi PBai YPYin YLWang JZWang LRen FLu CBChen YZhu MLLiu CWang QQfalseNitrosative stress induced by homocysteine thiolactone drives vascular cognitive impairments via GTP cyclohydrolase 1 S-nitrosylation in vivo.<h4>Background</h4>s: Hyperhomocysteinemia (HHcy) is one of risk factors for vascular cognitive impairment (VCI). GTP cyclohydrolase 1 (GCH1) deficiency is critical to oxidative stress in vascular dysfunction. The aim of this study was designed to examine whether HHcy induces VCI through GCH1 S-nitrosylation, a redox-related post-translational modification of cysteine.<h4>Methods</h4>The VCI model was induced by feeding mice homocysteine thiolactone (HTL) for 16 consecutive weeks. The cognitive functions were evaluated by step-down avoidance test, passive avoidance step-through task test, and Morris water maze (MWM) test. Protein S-nitrosylation was assayed using a biotin-switch method.<h4>Results</h4>In cell-free system, nitric oxide (NO) donor induced GCH1 protein S-nitrosylation and dec2022-01-01T00:00:00Z2022 Nov2025-04-18T14:59:31.812Z2025-04-07T01:24:12.654ZS-EPMC96731093639995710.1016/j.redox.2022.102540