Renal dysfunction in adults following cardiopulmonary bypass is linked to declines in S-nitroso hemoglobin: a case series.

Background: Impaired kidney function is frequently observed in patients following cardiopulmonary bypass (CPB). Our group has previously linked blood transfusion to acute declines in S-nitroso haemoglobin (SNO-Hb; the main regulator of tissue oxygen delivery), reductions in intraoperative renal blood flow, and postoperative kidney dysfunction. While not all CPB patients receive blood, kidney injury is still common.

Protocol for preparing Thiopropyl Sepharose resin used for capturing S-nitrosylated proteins.

S-nitrosothiol (SNO)-Resin Assisted Capture (SNO-RAC) relies on a Thiopropyl Sepharose resin to identify S-nitrosylated proteins (SNO-proteins) and sites of S-nitrosylation. Here, we present a protocol for preparing Thiopropyl Sepharose resin with efficiency of SNO-protein capture comparable to the discontinued commercial version. We describe steps for amine coupling, disulfide reduction, and generation of thiol reactive resin.

Identification of a Selective SCoR2 Inhibitor That Protects Against Acute Kidney Injury.

Acute kidney injury (AKI) is associated with high morbidity and mortality, and no drugs are available clinically. Metabolic reprogramming resulting from the deletion of S-nitroso-coenzyme A reductase 2 (SCoR2; AKR1A1) protects mice against AKI, identifying SCoR2 as a potential drug target. Of the few known inhibitors of SCoR2, none are selective versus the related oxidoreductase AKR1B1, limiting therapeutic utility.

Control of tissue oxygenation by S-nitrosohemoglobin in human subjects.

S-Nitrosohemoglobin (SNO-Hb) is unique among vasodilators in coupling blood flow to tissue oxygen requirements, thus fulfilling an essential function of the microcirculation. However, this essential physiology has not been tested clinically. Reactive hyperemia following limb ischemia/occlusion is a standard clinical test of microcirculatory function, which has been ascribed to endothelial nitric oxide (NO).

S-nitrosylation is required for βAR desensitization and experimental asthma.

The β-adrenergic receptor (βAR), a prototypic G-protein-coupled receptor (GPCR), is a powerful driver of bronchorelaxation, but the effectiveness of β-agonist drugs in asthma is limited by desensitization and tachyphylaxis. We find that during activation, the βAR is modified by S-nitrosylation, which is essential for both classic desensitization by PKA as well as desensitization of NO-based signaling that mediates bronchorelaxation. Strikingly, S-nitrosylation alone can drive βAR internalization in the absence of traditional agonist.