@entity12325 ( @entity5322 ) is the most abundant @entity11670 protein in @entity1 liver and intestine and is highly inducible by a variety of drugs and other compounds. The @entity11670 catalytic cycle is known to uncouple and release reactive @entity26 species (ROS), but the effects of ROS from @entity11670 and other enzymes in the endoplasmic reticulum have been poorly studied from the perspective of effects on cell biology. In this study, we expressed low levels of @entity5322 in HepG2 cells, a @entity1 hepatocarcinoma cell line, and examined effects on intracellular levels of ROS and on the secretion of a variety of growth factors that are important in extracellular communication. Using the redox-sensitive dye RedoxSensor red, we demonstrate that @entity5322 expression increases levels of ROS in viable cells. A custom ELISA microarray platform was employed to demonstrate that expression of @entity5322 increased secretion of @entity1915 , intracellular adhesion molecule 1, matrix metalloprotease 2, platelet-derived growth factor (PDGF), and @entity7 , but suppressed secretion of @entity5750 . The antioxidant @entity898 suppressed all @entity11670 -dependent changes in protein secretion except for @entity5750 . Quantitative RT-PCR demonstrated that changes in protein secretion were consistently associated with corresponding changes in gene expression. Inhibition of the NF-kB pathway blocked @entity11670 effects on PDGF secretion. @entity5322 expression also altered protein secretion in @entity1 mammary epithelial cells and @entity23882 @entity19 lung cells. Overall, these results suggest that increased ROS production in the endoplasmic reticulum alters the secretion of proteins that have key roles in paracrine and autocrine signaling.

Reactive XXXX species alter autocrine and paracrine signaling.

@entity1 :: ('9606', 'Species') :: ['human'] @entity11670 :: ('1555', 'Gene') :: ['P450'] @entity1915 :: ('374', 'Gene') :: ['amphiregulin'] @entity12325 :: ('4051', 'Gene') :: ['Cytochrome P450 (P450) 3A4'] @entity7 :: ('7422', 'Gene') :: ['vascular endothelial growth factor'] @entity5322 :: ('1576', 'Gene') :: ['CYP3A4'] @entity5750 :: ('929', 'Gene') :: ['CD14'] @entity26 :: ('MESH:D010100', 'Chemical') :: ['oxygen'] @entity23882 :: ('3226', 'Gene') :: ['C10'] @entity19 :: ('10090', 'Species') :: ['mouse'] @entity898 :: ('MESH:D000111', 'Chemical') :: ['N-acetylcysteine']
@entity26 :: (MESH:D010100,Chemical) :: ['oxygen']
