Cardiac overexpression of a mitochondrial SUR2A splice variant impairs cardiac function and worsens myocardial ischemia reperfusion injury in female mice.

The small splice variant of the sulfonylurea receptor protein isoform 2 A (SUR2A-55) targets mitochondria and enhances mitoK activity. In male mice the overexpression of this protein promotes cardioprotection, reducing myocardial injury after an ischemic insult. However, it is unclear what impact SUR2A-55 overexpression has on the female myocardium.

Indirect cardiac output assessment in a swine pediatric acute respiratory distress syndrome model.

Purpose: To investigate the correlation between volume of carbon dioxide elimination (V̇CO) and end-tidal carbon dioxide (PETCO) with cardiac output (CO) in a swine pediatric acute respiratory distress syndrome (ARDS) model.

Methods: Respiratory and hemodynamic variables were collected from twenty-six mechanically ventilated juvenile pigs under general anesthesia before and after inducing ARDS, using oleic acid infusion.

Results: Prior to ARDS induction, mean (SD) CO, V̇CO, PETCO, and dead space to tidal volume ratio (V/V) were 4.

Overexpression of a Short Sulfonylurea Splice Variant Increases Cardiac Glucose Uptake and Uncouples Mitochondria by Regulating ROMK Activity.

The mitochondrial splice variant of the sulfonylurea receptor (SUR2A-55) is associated with protection from myocardial ischemia-reperfusion (IR) injury, increased mitochondrial ATP sensitive K channel activity (mitoK) and altered glucose metabolism. While mitoK channels composed of CCDC51 and ABCB8 exist, the mitochondrial K pore regulated by SUR2A-55 is unknown. We explored whether SUR2A-55 regulates ROMK to form an alternate mitoK.

The p52 isoform of SHC1 is a key driver of breast cancer initiation.

Background: SHC1 proteins (also called SHCA) exist in three functionally distinct isoforms (p46SHC, p52SHC, and p66SHC) that serve as intracellular adaptors for several key signaling pathways in breast cancer. Despite the broad evidence implicating SHC1 gene products as a central mediator of breast cancer, testing the isoform-specific roles of SHC1 proteins have been inaccessible due to the lack of isoform-specific inhibitors or gene knockout models.

Methods: Here, we addressed this issue by generating the first isoform-specific gene knockout models for p52SHC and p66SHC, using germline gene editing in the salt-sensitive rat strain.