title: Homocysteine in Chronic Kidney Disease.
abstract: Hyperhomocysteinemia occurs in chronic- and end-stage kidney disease at the time when dialysis or transplant becomes indispensable for survival. Excessive accumulation of homocysteine (Hcy) aggravates conditions associated with imbalanced homeostasis and cellular redox thereby resulting in severe oxidative stress leading to oxidation of reduced free and protein-bound thiols. Thiol modifications such as N-homocysteinylation, sulfination, cysteinylation, glutathionylation, and sulfhydration control cellular responses that direct complex metabolic pathways. Although cysteinyl modifications are kept low, under Hcy-induced stress, thiol modifications persist thus surpassing cellular proteostasis. Here, we review mechanisms of redox regulation and show how cysteinyl modifications triggered by excess Hcy contribute development and progression of chronic kidney disease. We discuss different signaling events resulting from aberrant cysteinyl modification with a focus on transsulfuration.
authors.affiliation: Frontiers in Bioscience Research Institute in Aging and Cancer, Irvine, California, USA. Electronic address: eostrakh@uwo.ca.
authors.forename: Elena A
authors.initials: EA
authors.lastname: Ostrakhovitch
authors.affiliation: Frontiers in Bioscience Research Institute in Aging and Cancer, Irvine, California, USA.
authors.forename: Siamak
authors.initials: S
authors.lastname: Tabibzadeh
mesh_terms: D006710:Homocysteine / Q000097:blood*; D006801:Humans; D020138:Hyperhomocysteinemia / Q000209:etiology*; D007676:Kidney Failure, Chronic / Q000097:blood*; D008745:Methylation; D010084:Oxidation-Reduction; D018384:Oxidative Stress
chemical_list: D006710:Homocysteine
keywords: Cysteine-targeted oxidation/thiolation; Homocysteine; Hydrogen sulfide; Kidney; Podocytes; Protein posttranslation modification; Redox regulation; Sulfhydration; Transsulfuration pathway