S-nitrosylation: a radical way to protect the heart

Abstract

In this review, the role of S-nitrosylation (SNO) in cardioprotection will be discussed. This review will cover the methodology used to measure SNO levels, and the mechanisms by which SNO serves to modulate cell function and mediate protection. We will also consider whether SNO acts through many targets or whether there are a few key SNO proteins that mediate protection. Issues regarding the percentage of the total protein which is SNO and how this plays a role in the modulation of cell function will also be discussed. The role of nitric oxide synthase uncoupling in cardioprotection will also be addressed. This article is part of a Special Section entitled "Post-translational Modification."

Figure 1

Panel 1A illustrates the protocol for the DyLight switch. Panel 1B shows a representative 2D-gel where control samples are pseudo-colored in green and GSNO treated samples are in red.

Figure 2

A comparison of proteins identified with 2D-DyLight switch versus those identified with SNO-RAC. There were 4 common proteins identified with both SNO-RAC and the 2D gel. There wer proteins that were only identified with SNO-RAC and 13 proteins that were only identified with the 2D-gel method.

Figure 3

Preconditioning increases SNO which can shield thiol groups from irreversible oxidation.

Figure 4

SNO of GAPDH protects from oxidation.

Figure 5

Localized NOS signaling can result in targeted SNO. This is a hypothetical depiction of how localized signaling could play a role in signaling and why it is important to understand the localization of SNO as well as the total percentage of a protein that is SNO. For example if there is only 20% modification of a protein (protein X) and the modification is uniformly distributed, this would have a different effect on the cell than if for example 20% of the protein was localized in a compartment (e.g. mitochondria) and all of the protein in this compartment was SNO.