"The ubiquitin ligase SIAH2 is a female-specific regulator of circadian rhythms and metabolism".

Circadian clocks enable organisms to predict and align their behaviors and physiologies to constant daily day-night environmental cycle. Because the ubiquitin ligase Siah2 has been identified as a potential regulator of circadian clock function in cultured cells, we have used SIAH2-deficient mice to examine its function in vivo. Our experiments demonstrate a striking and unexpected sexually dimorphic effect of SIAH2-deficiency on the regulation of rhythmically expressed genes in the liver.

The E3 Ligases Spsb1 and Spsb4 Regulate RevErbα Degradation and Circadian Period.

The time-dependent degradation of core circadian clock proteins is essential for the proper functioning of circadian timekeeping mechanisms that drive daily rhythms in gene expression and, ultimately, an organism's physiology. The ubiquitin proteasome system plays a critical role in regulating the stability of most proteins, including the core clock components. Our laboratory developed a cell-based functional screen to identify ubiquitin ligases that degrade any protein of interest and have started screening for those ligases that degrade circadian clock proteins.

Eplerenone inhibits aldosterone-induced renal expression of cyclooxygenase.

Introduction: The upregulation of cyclooxygenase (COX) expression by aldosterone (ALDO) or high salt diet intake is very interesting and complex in the light of what is known about the role of COX in renal function. Thus, in this study, we hypothesize that apocynin (APC) and/or eplerenone (EPL) inhibit ALDO/salt-induced kidney damage by preventing the production of prostaglandin E₂ (PGE₂).

Methods: Dahl salt-sensitive rats on either a low-salt or high-salt diet were treated with ALDO (0.

The involvement of prostaglandins in the contractile function of the aorta by aldosterone.

Background: Aldosterone, one of the major culprits associated with the renin-angiotensin-aldosterone system (RAAS), is significantly elevated following high salt administration in Dahl rats. Since we have previously demonstrated that aldosterone (ALDO) upregulates cyclooxygenase (COX) expression in the kidney, the present study was design to assess whether prostaglandin release is involved in the effects of chronic aldosterone treatment on vascular function of the aorta from nonhypertensive Dahl salt-sensitive rats.

Findings: The effects of aldosterone on arachidonic acid metabolism and on the expression of cyclooxygenase (COX)-2 were evaluated in the Dahl salt sensitive (DS) rat aorta, renal, femoral and carotid arteries.

Eplerenone suppresses aldosterone/ salt-induced expression of NOX-4.

Introduction: Salt-induced hypertension in the Dahl rat is associated with increases in angiotensin II, aldosterone, free radical generation and endothelial dysfunction. However, little is known about the specific mechanism(s) associated with the end-organ damage effects of aldosterone. We hypothesised that eplerenone reduces kidney damage by blocking nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activity.