Dityrosine suppresses the cytoprotective action of thyroid hormone T3 via inhibiting thyroid hormone receptor-mediated transcriptional activation.

Dityrosine (Dityr) is the most common oxidized form of tyrosine. In the previous studies of mice treated with dityrosine, cell death in the pancreas, kidneys, and liver was detected in the presence of enhanced plasma triiodothyronine (T3) content. Due to its structural similarity with the thyroid hormone T3, we hypothesized that dityrosine might disrupt T3-dependent endocrine signaling. The cytotoxic effect of dityrosine was studied in C57BL/6 mice by gavage with a dityrosine dose of 320 µg per kg per day for 10 weeks. Cell death in the liver was detected in the presence of enhanced plasma thyroid hormone content in mice treated with dityrosine. The antagonistic effect of dityrosine on T3 biofunction was studied using HepG2 cells. Dityrosine incubation reduced T3 transport ability and attenuated the T3-mediated cell survival via regulation of the PI3k/Akt/MAPK pathway. Furthermore, dityrosine inhibited T3 binding to thyroid hormone receptors (TRs) and suppressed the TR-mediated transcription. Dityrosine also downregulated the expressions of T3 action-related factors. Taken together, this study demonstrates that dityrosine inhibits T3-dependent cytoprotection by competitive inhibition, resulting in downstream gene suppression. Our findings offer insights into how dityrosine acts as an antagonist of T3. These findings shed new light on cellular processes underlying the energy metabolism disorder caused by dietary oxidized protein, thus contributing to a better understanding of the diet-health axis at a cellular level.

Propofol postconditioning protects H9c2 cells from hypoxia/reoxygenation injury by inducing autophagy via the SAPK/JNK pathway.

Propofol postconditioning (P­PostC) offers cardioprotection in mice, and the upregulation of autophagy protects cardiac cells against ischemia/reperfusion injury. The present study aimed to examine the effects of P­PostC on the induction of autophagy and its potential roles in hypoxia/reoxygenation (H/R) injury. Rat heart­derived H9c2 cells were exposed to H/R, comprising 6 h of hypoxia followed by 4 h of reoxygenation, as well as postconditioning with various concentrations of propofol at the onset of reperfusion. Lactate dehydrogenase (LDH) activity and the rate of cell apoptosis were measured to evaluate the degree of cardiomyocyte H/R injury. The induction of autophagy in myocytes subjected to H/R injury and P­PostC was detected by western blotting and immunofluorescence. Furthermore, the activation of c­Jun N­terminal kinase (JNK) in cells treated with P­PostC with or without co­treatment with SP600125, an inhibitor of JNK, was also determined by western blotting. P­PostC reduced the activity of LDH in the culture medium and the percentage of apoptotic cells compared with cells in the untreated H/R group. In addition, P­PostC induced autophagy and promoted survival signaling in H9c2 cardiac myoblast cells. The inhibition of autophagy by 3­methyladenine treatment diminished the cardioprotective effects of P­PostC. These results indicated that propofol postconditioning promoted cell survival through the induction of autophagy in H9c2 cardiac cells, and that the stress­activated protein kinase/JNK survival pathway may be partly involved in P­PostC­induced autophagy.

[Studies of potassium channel in pulmonary artery smooth muscle cells derived from renal hypertensive rat].

AIM: To investigate the differences of membrane capacitance, membrane current, current density and I-V curves between smooth muscle cells isolated from RHR and NTR pulmonary arteries. METHODS: Under antiseptic conditions, the left renal artery was exposed through a retroperitoneal flank incision and carefully dissected free of the left renal vein. A silver clip with an internal diameter of 0.2-0.3 mm was placed around the left renal artery, resulting in partial occlusion of renal perfusion. SBP was observed by tail blood pressure. Whole cell recordings were made from smooth muscle cells freshly isolated from pulmonary arteries derived from RHR or NTR. RESULTS: The average membrane capacitance was (3.43 +/- 1.16) pF, decreased by 31.1%; membrane current was (0.54 +/- 0.26) nA, decreased by 68.2%; current density was (180 +/- 90) pA/pF, decreased by 48.6%; membrane potential was (-26.96 +/- 7.23) mV, decreased by 2.5%, all compared with that of NTR respectively. Iptakalim hydrochloride at the concentration of 0.1-100 micromol/L can significantly increased NTR potassium currents. Iptakalim hydrochloride 1-100 micromol/L can significantly increased RHR potassium currents. CONCLUSION: Membrane capacitance, membrane current, membrane potential were decreased, I-V curves were shift downward, compared with that of NTR. Iptakalim hydrochloride might significantly increase NTR and RHR potassium currents.