title: Are nitric oxide-mediated protein modifications of functional significance in diabetic heart? ye'S, -NO', wh'Y-NO't?
abstract: Protein modifications effected by nitric oxide (NO) primarily in conjunction with reactive oxygen species (ROS) include tyrosine nitration, cysteine S-nitrosylation, and glutathionylation. The physiological and pathological relevance of these three modifications is determined by the amino acids on which these modifications occur -cysteine and tyrosine, for instance, ranging from altering structural integrity/catalytic activity of proteins or by altering propensity towards protein degradation. Even though tyrosine nitration is a well-established nitroxidative stress marker, instilled as a footprint of oxygen- and nitrogen-derived oxidants, newer data suggest its wider role in embryonic heart development and substantiate the need to focus on elucidating the underlying mechanisms of reversibility and specificity of tyrosine nitration. S-nitrosylation is a covalent modification in specific cysteine residues of proteins and is suggested as one of the ways in which NO contributes to its ubiquitous signalling. Several sensitive and specific techniques including biotin switch assay and mass spectrometry based analysis make it possible to identify a large number of these modified proteins, and provide a great deal of potential S-nitrosylation sites. The number of studies that have documented nitrated proteins in diabetic heart is relatively much less compared to what has been published in the normal physiology and other cardiac pathologies. Nevertheless, elucidation of nitrated proteome of diabetic heart has revealed the presence of many mitochondrial and cytosolic proteins of functional importance. But, the existence of different models of diabetes and analyses at diverse stages of this disease have impeded scientists from gaining insights that would be essential to understand the cardiac complications during diabetes. This review summarizes NO mediated protein modifications documented in normal and abnormal heart physiology including diabetes.
authors.affiliation: Department of Biochemistry, Sree Chitra Tirunal Institute for Medical Sciences and Technology, Thiruvananthapuram 695011, India.
authors.forename: Nandini Ravikumar
authors.initials: NR
authors.lastname: Jayakumari
authors.affiliation: Department of Biochemistry, Sree Chitra Tirunal Institute for Medical Sciences and Technology, Thiruvananthapuram 695011, India.
authors.forename: Anand Chellappan
authors.initials: AC
authors.lastname: Reghuvaran
authors.affiliation: Department of Biochemistry, Sree Chitra Tirunal Institute for Medical Sciences and Technology, Thiruvananthapuram 695011, India.
authors.forename: Raji Sasikala
authors.initials: RS
authors.lastname: Rajendran
authors.affiliation: Department of Cardiovascular and Thoracic Surgery, Sree Chitra Tirunal Institute for Medical Sciences and Technology, Thiruvananthapuram 695011, India.
authors.forename: Vivek Velayudhan
authors.initials: VV
authors.lastname: Pillai
authors.affiliation: Department of Cardiovascular and Thoracic Surgery, Sree Chitra Tirunal Institute for Medical Sciences and Technology, Thiruvananthapuram 695011, India.
authors.forename: Jayakumar
authors.initials: J
authors.lastname: Karunakaran
authors.affiliation: Division of Laboratory Animal Sciences, Sree Chitra Tirunal Institute for Medical Sciences and Technology, Thiruvananthapuram 695011, India.
authors.forename: Harikrishnan Vijayakumar
authors.initials: HV
authors.lastname: Sreelatha
authors.affiliation: Department of Biochemistry, Sree Chitra Tirunal Institute for Medical Sciences and Technology, Thiruvananthapuram 695011, India. Electronic address: srinivasg@sctimst.ac.in.
authors.forename: Srinivas
authors.initials: S
authors.lastname: Gopala
mesh_terms: D003920:Diabetes Mellitus / Q000503:physiopathology; D006331:Heart Diseases / Q000503:physiopathology*; D006801:Humans; D009569:Nitric Oxide / Q000378:metabolism*; D046188:Protein Modification, Translational
chemical_list: D009569:Nitric Oxide
keywords: Diabetes; Nitration; Nitric oxide; Post translational modifications; S-nitrosylation