BACKGROUND Evidence suggestive of endoplasmic reticulum (ER) stress in the pulmonary arteries of patients with pulmonary arterial hypertension has been described for decades but has never been therapeutically targeted. ER stress is a feature of many conditions associated with pulmonary arterial hypertension like hypoxia, inflammation, or loss-of-function mutations. ER stress signaling in the pu...

21 Background: Endoplasmic reticulum (ER) stress has been implicated in the pathogenesis of nonalcoholic 22 steatohepatitis. The ER stress response is activated in the livers of mice fed a methionineand choline23 deficient (MCD) diet yet the role of ER stress in the pathogenesis of MCD diet-induced steatohepatitis is 24 unknown. We aim to determine the effects of reducing ER stress using chemic...

Endoplasmic reticulum (ER) stress has been implicated in the pathogenesis of nonalcoholic steatohepatitis. The ER stress response is activated in the livers of mice fed a methionine- and choline-deficient (MCD) diet, yet the role of ER stress in the pathogenesis of MCD diet-induced steatohepatitis is unknown. Using chemical chaperones on hepatic steatosis and markers of inflammation and fibrosi...

More than 200 heterozygous mutations in the type 2 BMP receptor gene, BMPR2, have been identified in patients with Heritable Pulmonary Arterial Hypertension (HPAH). More severe clinical outcomes occur in patients with BMPR2 mutations by-passing nonsense-mediated mRNA decay (NMD negative mutations). These comprise 40% of HPAH mutations and are predicted to express BMPR2 mutant products. However ...

Proteases and chaperones together serve to maintain quahty control of cellular proteins. Both types of en­ zymes have as their substrates the variety of misfolded and partially folded proteins that arise from slow rates of folding or assembly, chemical or thermal stress, intrinsic structural instability, and biosynthetic errors. The pri­ mary function of classical chaperones, such as the Esch­ ...

A complex pathway involving many molecular chaperones has been proposed for the folding, assembly, and maintenance of a high-affinity ligand-binding form of steroid receptors in vivo, including the glucocorticoid receptor. To better understand this intricate folding and assembly process, we studied the folding of the ligand-binding domain of the glucocorticoid receptor in vitro. We found that t...