Pre-treatment of the beta3-adrenergic receptor agonist BRL37344 reduces in vivo myocardial ischemia/reperfusion injury by improving AMPK and SIRT1 activity and by suppressing mTOR and p70S6K signaling pathways

Abstract This study aimed to investigate the role and signaling pathways of β3-AR in myocardial ischemia/reperfusion (I/R) injury, which is one of the leading causes of death worldwide. 47 male rats were randomly divided into two main groups to evaluate infarct size and molecular parameters. Rats in both groups were randomly divided into 4 groups. Control (sham), I/R (30 min ischemia/120 min reperfusion), BRL37344 (BRL) (A) (5 µg/kg single-dose pre-treatment (preT) before I/R) and BRL (B) (5 µg/kg/day preT for 10 days before I/R). Infarct size was determined with triphenyltetrazolium chloride staining and analyzed with ImageJ program. The levels of AMPK, SIRT1, mTOR, and p70SK6 responsible for cellular energy and autophagy were evaluated by western blot. Infarct size increased in the I/R group (44.84 ± 1.47%) and reduced in the single-dose and 10-day BRL-treated groups (32.22 ± 1.57%, 29.65 ± 0.55%; respectively). AMPK and SIRT1 levels were decreased by I/R but improved in the treatment groups. While mTOR and p70S6K levels increased in the I/R group, they decreased with BRL preT. BRL preT protects the heart against I/R injury. These beneficial effects are mediated in part by activation of AMPK and SIRT1, inhibition of mTOR and p70S6K, and consequently protected autophagy.

Molecular biology investigation of diabetes cystopathy in rats:relationship beween bladder relaxation characters and 3-adrenergic receptor level / 中华泌尿外科杂志

Objective To investigate the relationship beween bladder relaxation characters and 3-adrenergic receptor level in DM rats. Methods The studying subjects consist of induced diabetes and normal control rats,30 rats in each group,to detect bladder relaxation charaters in 2 groups and its relationship with 3-adrenergic receptor,cAMP contents.Western blot was performed to probe 3-adrenergic receptor.cAMP products of bladder was studied with radioimmunoassay. Results Bladder relaxation in response to isoproterenal stimulation was observed. Bladder pressure of streptozotocin induced diabetes rats at week 2,4,12 were (11.8?2.3),(11.9?2.2),(11.5?3.0)cm H_2O respectively,and (32.8?7.6),(33.9? 5.2 ),(34.7?2.7)cm H_2O in control group.3-adrenergic receptor level in diabetes group were (104?7),(105?11),(126?14)?m at week 2,4,12,and in control group (151?11),(151?10),(152?13)?m.cAMP products were detected at the same time points,namely,(0.195?0.026),(0.198?0.030),( 0.109? 0.031)pmol/L in diabetes group,and (0.349?0.051),(0.350?0.052),(0.353?0.051)pmol/L in control group. Conclusions Relaxation abilities is impaired in diabetes bladder.Though 3-adrenergic receptor level was up-regulated,cAMP products is donw-regulated,which is responsible for detrusor relaxation.3-adrenergic receptor pathway is impaired via donw-regulating cAMP products in diabetes cystopathy.