Hypoxia tolerance in fish depends on catabolic preference between lipids and carbohydrates

Hypoxia is a common environmental stress factor in aquatic organisms,which varies among fish species.However,the mechanisms underlying the ability of fish species to tolerate hypoxia are not well known.Here,we showed that hypoxia response in different fish species was affected by lipid catabolism and preference for lipid or carbohydrate energy sources.Activation of biochemical lipid catabolism through peroxisome proliferator-activated receptor alpha(Pparα)or increasing mitochondrial fat oxidation in tilapia decreased tolerance to acute hypoxia by increasing oxygen consumption and oxidative damage and reducing carbohydrate catabolism as an energy source.Conversely,lipid catabolism inhibition by suppressing entry of lipids into mitochondria in tilapia or individually knocking out three key genes of lipid catabolism in zebrafish increased tolerance to acute hypoxia by decreasing oxygen consumption and oxidative damage and promoting carbohydrate catabolism.However,anaerobic glycolysis suppression eliminated lipid catabolism inhibition-promoted hypoxia tolerance in adipose triglyceride lipase(atgl)mutant zebrafish.Using 14 fish species with different trophic levels and taxonomic status,the fish preferentially using lipids for energy were more intolerant to acute hypoxia than those preferentially using carbohydrates.Our study shows that hypoxia tolerance in fish depends on catabolic preference for lipids or carbohydrates,which can be modified by regulating lipid catabolism.

Rates of oxygen consumption and tolerance of hypoxia and desiccation in Chinese black sleeper(Bostrichthys sinensis)and mudskipper(Boleophthalmus pectinirostris)embryos

The rates of oxygen consumption, tolerance of hypoxia and desiccation of the Chinese black sleeper （ Bostrichthys sinensis） and mudskipper （Boleophthalmus pectinirostris） embryos were investigated. The pattern of oxygen consumption of the Chinese black sleeper embryos was similar to that of the mudskipper ones. The lowest rates of oxygen consumption [ （ 1.65 ±0. 66） nmol/ （ind. ·h） ] of the Chinese black sleeper embryos 16 h after fertilization and the lowest rates of oxygen consumption [ （0.79± 0.08 ）nmolf（ ind. · h） ] of the mudskipper embryos 6 h after fertilization were recorded, respectively. Then the rates of oxygen consumption of these two species embryos increased gradually until hatching [ （8.26 ± 1.70 ） nmolf（ ind.· h） in the Chinese black sleeper, （2.69 ± 0.23 ）nmolf（ ind. · h） in mudskipper]. After exposure to hypoxia water （0.16 mg/dm^3）, bradycardia of the embryos occurred in both the Chinese black sleeper and the mudskipper. However, the Chinese black sleeper embryos survived approximately 45 min longer than the mudskipper ones. After exposure to desiccation at a relative humidity of 58%, bradycardia of the embryos was observed in both the Chinese black sleeper and the mudskipper, and the Chinese black sleeper embryos lived approximately 9 min longer than the mudskipper ones.

Expression of hypoxia inducible factor-1 alpha and ischemic erythropoietin tolerance in the brain of cerebral ischemic tolerance model rats

BACKGROUND： Hypoxia inducible factor-1 alpha （HIF-1 （x） and erythropoietin（EPO）, possessing neuroprotective effect in the cerebral ischemia, might play an important role in the formation of cerebral ischemic tolerance （IT）. OBJECTIVE：To observe the neuroprotective effect of cerebral ischemic preconditioning（IPC） of rats, and the expression and mechanism of HIF-1α and target gene erythropoietin in the brain tissue following the formation of cerebral IT. DESIGN ： A randomized and controlled observation SETTING： Department of Neurology, the Affiliated Hospital of Medical College, Qingdao University MATERIALS： Totally 84 enrolled adult healthy male Wistar rats of clean grade, weighing 250 to 300 g, were provided by the Animal Experimental Department, Tongji Medical College of Huazhong University of Science and Technology. Ready-to-use SABC reagent kit and rabbit anti-rat HIF-1α monoclonal antibody were purchased from Boshide Bioengineering Co.Ltd （Wuhan）; Rabbit anti-rat EPO monoclonal antibody was purchased from Santa Cruz Company （USA）. METHODS： This experiment was carried out in the Department of Anatomy, Medical College, Qingdao University during March 2005 to March 2006. ① The 84 rats were divided into 3 groups by a lot： IPC group （n=40）, sham-operation group （n=40） and control group （n=4）. In the IPC group, middle cerebral artery was occluded for 2 hours respectively on the 1^st, 3^rd, 7^th, 14^th and 21^st days of the reperfusion following 10-minute preischemia was made using a modified middle cerebral artery second suture method from Zea-Longa. The rats were sacrificed 22 hours after reperfusion in the end of middle cerebral artery occlusion （MCAO）. That was to say, after 10-minute preischemia, suture was exited to the extemal carotid artery and embedded subcutaneously. Middle cerebral artery was occluded again to form the second reperfusion at the set time point after reperfusion. Twenty-two hours later, rats were sacrificed; In the sham-operation group,the preischemia was substituted by sham-operation（only common carotid artery and crotch were exposed, and MCAO by suture was omitted）, and the other procedures were the same as those in the IPC group. In the control group, rats were given sham-operation twice at an interval of one day, and they were sacrificed 24 hours after the second sham-operation. ② Brain tissue was taken from the rats in each group. Cerebral infarction area of each layer was measured with TTC staining, and total cerebral infarction volume （The total cerebral infarction area of each layerxinterspace ） was calculated. After brain tissue was stained by haematoxylin-esoin （HE）, the form of nerve cells was observed under an optical microscope, and the expressions of HIF-1α（and EPO protein in the brain tissue were detected with immunohistochemical method. MAIN OUTCOME MEASURES： ①Cerebral infarction volume;②form of nerve cell; ③ the expression of HIF-1α and EPO protein in the brain tissue. RESULTS：Totally 84 rats were enrolled in the experiment. The dead rats were randomly supplied during the experiment, and finally 84 rats entered the stage of result analysis. ① Detection of cerebral infarction volume of rats in each group： Cerebral infarction volume in the IPC group was significantly smaller than that in the sham-operation group on the 1^st, 3^rd and 7^th days after reperfusion respectively [（161.2±6.9） mm^3 vs （219.9±11.2） mm^3, （134.9±9.0） mm^3 vs （218.6±13.0） mm^3, （142.9±13.7） mm^3 vs （221.3±14.2） mm^3, t=-8.924, 10.587,7.947, P〈 0.01]. ② Observation of nerve cell form of brain tissue： HE staining showed that the ischemic degree, range and cerebral edema degree of IPC group were significantly milder than those of sham-operation group. ③ The expressions of HIF-1α and EPO protein in cerebral cortex and hippocampus ： The expression of HIF-1αof IPC group was significantly higher than that of sham-operation group on the 1^st, 3^rd and 7^th days after reperfusion respectively （125.93±3.79 vs 117.65±5.60, 140.63±4.64 vs 119.33±4.26, 131.15±2.74 vs 107.60±3.89, t=2.449, 6.763,9.899,P 〈 0.05-0.01）. The expression of EPO of IPC group was significantly higher than that of sham-operation group on the 3^rd and 7^th days after perfusion respectively （141.68±3.29 vs 126.33±4.51, 138.88±2.59 vs 125.58±6.18,t=5.499,3.970, P〈 0.05）. CONCLUSION ： ①IPC can protect the never cells in rat brain and the best time to onset of cerebral IT induced by IPC is 1 to 7 days after reperfusion. ② Neuroprotective effect of cerebral IT might be related to the expression of HIF-1α and its target gene EPO.

The Protective Effects of In Vitro Cultivated Calculus Bovis on the Cerebral and Myocardial Cells in Hypoxic Mice

The protective effects of in vitro cultivated calculus bovis （ICCB） on the cerebral and myocardial cells in hypoxic mice and the mechanism were examined. In one group, mice were intragastrically （i.g.） given ICCB for 15 days and then they were subjected to acute cerebral ischemia by decapitation, and then the panting time was recorded. In the other group, 12 min after exposure to hypoxia, mice was administered the ICCB i.g. for 5 days, and then the blood serum and tissues of brain, heart, liver were harvested and examined for SOD, GSH-px and T-AOC activity and content of MDA. The tissues of brain and heart were observed electron-microscopically for ultrastructural changes. The corpus striatum and hippocampus of brain were collected and examined for content of dopamine （DA） and norepinephrine （NE）. The ultrastrural examination showed that the pathological change in brain and heart in the ICCB group was very slight, while abnormal changes in the control group were obviously more serious. ICCB significantly prolonged the panting time of the hypoxic mice （P〈0.001）, increased the activity of SOD, GSH-px, T-AOC in serum and tissues of brain, liver, heart and elevated the content of DA and NE. ICCB also pronouncedly reduced content of MDA in serum and tissues of brain, heart and liver. Significant differences in these parameters were noted between ICCB group and controls. It is concluded that ICCB can exert protective effect on the cells of brain and myocardium by enhancing the tolerance of the tissues to hypoxia and the body＇s ability to remove free radicals and regulating the neurotransmitters.