A pair of transporters controls mitochondrial Zn2+ levels to maintain mitochondrial homeostasis

Zn2+ is required for the activity of many mitochondrial proteins, which regulate mitochondrial dynamics, apoptosis and mitophagy. However, it is not understood how the proper mitochondrial Zn2+ level is achieved to maintain mitochondrial homeostasis. Using Caenorhabditis elegans, we reveal here that a pair of mitochondrion-localized transporters controls the mitochondrial level of Zn2+. We demonstrate that SLC-30A9/ZnT9 is a mitochondrial Zn2+ exporter. Loss of SLC-30A9 leads to mitochondrial Zn2+ accumulation, which damages mitochondria, impairs animal development and shortens the life span. We further identify SLC-25A25/SCaMC-2 as an important regulator of mitochondrial Zn2+ import. Loss of SLC-25A25 suppresses the abnormal mitochondrial Zn2+ accumulation and defective mitochondrial structure and functions caused by loss of SLC-30A9. Moreover, we reveal that the endoplasmic reticulum contains the Zn2+ pool from which mitochondrial Zn2+ is imported. These findings establish the molecular basis for controlling the correct mitochondrial Zn2+ levels for normal mitochondrial structure and functions.

Comparison of landiolol and esmolol for treatment of intraoperative arrhythmia in dogs / 中华麻醉学杂志

Objective To compare landiolol and esmolol for treatment of intraoperative arrhythmia in dogs.Methods Experiment Ⅰ Eighty-eight KM mice (44 males, 44 females) , aged 4-6 weeks, were studied.The median lethal dose (LD50) and median effective dose (ED50) of landiolol and esmolol were determined using the sequential method.Treatment index (TI) was calculated.Experiment Ⅱ Eighteen dogs (9 males, 9 females), aged 8-12 months, weighing 7-10 kg, were equally and randomly divided into 3 groups: model group (group M) , landiolol group (group L) and esmolol group (group E).Intraoperative arrhythmia model was established by using gastrointestinal surgery combined with epinephrine.When sustained ventricular arrhythmias occurred, normal saline 0.5 ml/kg, landiolol 8.3 mg/kg and esmolol 10.0 mg/kg were given intravenously in C, L and E groups, respectively.The duration of arrhythmias was recorded.If bradycardia occurred (decrease in heart rate [HR] ≥ 25％ of the baseline value) , isoprenaline 0.05 mg/kg and atropine 0.03 mg/kg were injected intravenously.The occurrence of bradycardia after the initial administration of landiolol and esmolol, and the accumulated dose of landiolol and esmolol consumed when bradycardia occurred were recorded.Isoprenaline and atropine-induced improvement in bradycardia was recorded.Results Compared with esmolol, the LD50 and TI of landiolol were significantly increased (P＜0.01), and no significant change was found in ED50 of landiolol (P＞0.05).The duration of arrhythmias was significantly shorter in L and E groups than in group C, and in group L than in group E (P＜0.01).After the initial administration of landiolol and esmolol, the incidence of bradycardia was 0 and 100％, respectively, and the accumulated dose of landiolol and esmolol consumed when bradycardia occurred was (30± 13) mg/kg.Atropine could not effectively treat bradycardia, while isoprenaline could treat bradycardia.Compared with group L, the time for HR to rise and the duration for HR returning to the baseline value were significantly prolonged in group E (P＜0.05).Conclusion Compared with esmolol, landiolol provides faster improvement in intraoperative arrhythmia, weaker negative chronotropic effect, and higher safety;isoproterenol produces better efficacy in treating landiololinduced bradycardia in dogs.

Protective effects of penehyclidine hydrochloride on transient forebrain ischemia reperfusion injury in gerbils / 中国临床药理学与治疗学

AIM:To study the protective effects of penehyclidine hydrochloride(PHC) on transient forebrain ischemia reperfusion injury in gerbils.METHODS:The model of transient forebrain ischemia reperfusion was established in gerbils by bilateral carotid artery clamping.The effects of PHC on neurological function scores and the morphous of hippocampal pyramidal neuron of gerbils were observed after receiving transient forebrain ischemia reperfusion.SOD activities and contents of MDA in the hippocampus and cortex of gerbils were measured.RESULTS:In the groups of PHC(0.08),(0.24)(mg?kg~(-1)) and atropine,the stroke index was decreased,compared with the ischemia-reperfusion group after the gerbils received transient forebrain ischemia reperfusion for six hours.PHC could reduce the degree of injury in hippocampal pyramidal neuron after ischemia reperfusion for three days.CONCLUSION: PHC has protective effects on transient forebrain ischemia reperfusion injury in gerbils.