Current Therapeutic Landscape and Safety Roadmap for Targeting the Aryl Hydrocarbon Receptor in Inflammatory Gastrointestinal Indications.

Target modulation of the AhR for inflammatory gastrointestinal (GI) conditions holds great promise but also the potential for safety liabilities both within and beyond the GI tract. The ubiquitous expression of the AhR across mammalian tissues coupled with its role in diverse signaling pathways makes development of a "clean" AhR therapeutically challenging. Ligand promiscuity and diversity in context-specific AhR activation further complicates targeting the AhR for drug development due to limitations surrounding clinical translatability.

All--retinoic acid-mediated cytoprotection in LLC-PK renal epithelial cells is coupled to -ERK activation in a ROS-independent manner.

Although all--retinoic acid (ATRA) provides protection against a variety of conditions in vivo, particularly ischemia, the molecular mechanisms underpinning these effects remain unclear. The present studies were designed to assess potential mechanisms by which ATRA affords cytoprotection against renal toxicants in LLC-PK cells. Pretreatment of LLC-PK cells with ATRA (25 μM) for 24 h afforded cytoprotection against oncotic cell death induced by -aminophenol (PAP), 2-(glutathion--yl)hydroquinone (MGHQ), and iodoacetamide but not against apoptotic cell death induced by cisplatin.

Hepatic triacylglycerol hydrolysis regulates peroxisome proliferator-activated receptor alpha activity.

Recent evidence suggests that fatty acids generated from intracellular triacylglycerol (TAG) hydrolysis may have important roles in intracellular signaling. This study was conducted to determine if fatty acids liberated from TAG hydrolysis regulate peroxisome proliferator-activated receptor alpha (PPARalpha). Primary rat hepatocyte cultures were treated with adenoviruses overexpressing adipose differentiation-related protein (ADRP) or adipose triacylglycerol lipase (ATGL) or treated with short interfering RNA (siRNA) targeted against ADRP.