The polycystins are modulated by cellular oxygen-sensing pathways and regulate mitochondrial function.

Autosomal dominant polycystic kidney disease is caused by mutations in the genes encoding polycystin-1 (PC1) and polycystin-2 (PC2), which form an ion channel complex that may mediate ciliary sensory processes and regulate endoplasmic reticulum (ER) Ca release. Loss of PC1 expression profoundly alters cellular energy metabolism. The mechanisms that control the trafficking of PC1 and PC2, as well as their broader physiological roles, are poorly understood.

Development of a high-throughput mass spectrometry based analytical method to support an in vitro OATP1B1 inhibition screening assay.

Rationale: It is well known that the organic anion transporting polypeptide 1B1 (OATP1B1) plays a major role in the hepatic uptake of a range of drugs. To this end, it is pivotal that the potential for new molecular entities (NMEs) to inhibit OATP1B1 activity be assessed during early drug discovery. The work reported herein describes the development of a high-throughput analytical method to measure the clinically relevant probe substrate, pitavastatin, for the in vitro assessment of OATP1B1 inhibition.

Adiponectin in the heart and vascular system.

Adipose tissue is not only a storage depot for energy, but also an active endocrine tissue. Adipokines, hormones and cytokines secreted from adipocytes, relay information about energy stores to peripheral tissues throughout the body. Most adipokines are produced in direct proportion to fat mass, and many have proinflammatory or otherwise adverse effects on the cardiovascular system.