Adoptive passive transfer of rabbit beta1-adrenoceptor peptide immune cardiomyopathy into the Rag2-/- mouse: participation of the ER stress.

Auto-antibodies against the beta(1)-adrenoceptors are present in 30-40% of patients with dilated cardiomyopathy. Recently, a synthetic peptide corresponding to a sequence of the second extracellular loop of the human beta(1)-adrenoceptor (beta(1)-EC(II)) has been shown to produce endoplasmic reticulum (ER) stress, myocyte apoptosis and cardiomyopathy in immunized rabbits. To study the direct cardiac effects of anti-beta(1)-EC(II) antibody in intact animals and if they are mediated via beta(1)-adrenoceptor stimulation, we administered IgG purified from beta(1)-EC(II)-immunized rabbits to recombination activating gene 2 knock-out (Rag2(-/-)) mice every 2 weeks with and without metoprolol treatment.

Norepinephrine-induced oxidative stress causes PC-12 cell apoptosis by both endoplasmic reticulum stress and mitochondrial intrinsic pathway: inhibition of phosphatidylinositol 3-kinase survival pathway.

Norepinephrine (NE) induces endoplasmic reticulum (ER) unfolded protein response and reduces maturation and translocation of NE transporter to cell membrane via enhanced formation of reactive oxygen species in PC-12 cells. In the present study, we investigated whether ER stress is also implicated in the proapoptotic effect of NE. We found that the apoptotic effect of NE was associated with increased processing of ER-resident pro-caspase-12, cleavage of caspase-9 and -3, and mitochondrial release of cytochrome c.

Extracellular norepinephrine reduces neuronal uptake of norepinephrine by oxidative stress in PC12 cells.

Cardiac norepinephrine (NE) uptake activity is reduced in congestive heart failure. Our studies in intact animals suggest that this effect on the cardiac sympathetic nerve endings is caused by oxidative stress and/or NE toxic metabolites derived from NE. In this study, we investigated the direct effects of NE on neuronal NE uptake activity and NE transporter (NET), using undifferentiated PC12 cells.

Loss of cardiac sympathetic neurotransmitters in heart failure and NE infusion is associated with reduced NGF.

Sympathetic neurotransmitters are diminished in cardiac efferent nerve endings in congestive heart failure (CHF). Similar changes occur after exogenous norepinephrine (NE) infusion. Since NE reduces nerve growth factor (NGF) in cultured cardiomyocytes, we proposed to determine whether the loss of noradrenergic transmitters in the failing heart is caused by the NE-mediated reduction of NGF or its neurotrophic receptor tyrosine kinase A (TrKA).