Developmental and Liver Metabolite Changes Induced by TPhP Exposure in Brown Frog(Rana zhenhaiensis)Tadpoles

As an organophosphorus compound that frequently detected in water samples,triphenyl phosphate(TPhP)has been showed to have multiple toxicological effects on aquatic species.However,no attention has been paid to its potential impact on non-model amphibian species.Here,tadpoles of the Zhenhai brown frog(Rana zhenhaiensis)were exposed to different concentrations of TPh P(0,0.02 and 0.1 mg/L)throughout the developmental period to assess physiological and meta bolic impacts of TPh P exposure on amphibian larvae.After 30-day TPh P exposure,the developmental stage of tadpoles from the high-concentration treatment appeared to be more advanced than that from the other two treatments,but other measured traits(including body size,tail length and liver weight)did not differ among treatments.Metabolite profiles in tadpole livers based on liquid chromatographymass spectrometry(LC-MS)revealed a distinct metabolic disorder in exposed animals.Specifically,significant changes in various hepatic amino acids(such as glutamine,glutamate,valine and leucine)were observed.Overall,our results indicated that chronic TPhP exposure potentially caused developmental and hepatic physiological changes in R.zhenhaiensis tadpoles,although its impact on tadpole growth appeared to be minor.     

Zacopride selectively activates the Kir2.1 channel via a PKA signaling pathway in rat cardiomyocytes

We recently reported that zacopride is a selective inward rectifier potassium current (IK1 ) channel agonist, suppressing ventricular arrhythmias without affecting atrial arrhythmias. The present study aimed to investigate the unique pharmacological properties of zacopride. The whole-cell patch-clamp technique was used to study IK1 currents in rat atrial myocytes and Kir2.x currents in human embryonic kidney (HEK)-293 cells transfected with inward rectifier potassium channel (Kir)2.1, Kir2.2, Kir2.3, or mutated Kir2.1 (at phosphorylation site S425L). Western immunoblots were performed to estimate the relative protein expression levels of Kir2.x in rat atria and ventricles. Results showed that zacopride did not affect the IK1 and transmembrane potential of atrial myocytes. In HEK293 cells, zacopride increased Kir2.1 homomeric channels by 40.7%±9.7% at 50 mV, but did not affect Kir2.2 and Kir2.3 homomeric channels, and Kir2.1-Kir2.2, Kir2.1-Kir2.3 and Kir2.2-Kir2.3 heteromeric channels. Western immunoblots showed that similar levels of Kir2.3 protein were expressed in rat atria and ventricles, but atrial Kir2.1 protein level was only 25% of that measured in the ventricle. In addition, 5-hydroxytryptamine (5-HT) 3 receptor was undetectable, whereas 5-HT 4 receptor was weakly expressed in HEK293 cells. The Kir2.1-activating effect of zacopride in these cells was abolished by inhibition of protein kinase A (PKA), but not PKC or PKG. Furthermore, zacopride did not activate the mutant Kir2.1 channel in HEK293 cells but selectively activated the Kir2.1 homomeric channel via a PKA-dependent pathway, independent to that of the 5-HT receptor.     

Identification of an kB-like motif at the 5' upstream region of human lymphotoxin gene

INTR0DUCTIONLymphotoxin(LT),alsocalledtum0rnecrosisfactord(TNF-P),isalymphokinereleasedbymit0genorantigen-activatedTlymphocytes.Undercircumstancesofvariousneoplastandautoimmunediseases,LTpr0ducti0ncanals0bedetectedre-spectively,contributingtothecytotoxici…