Overexpression of Rcan1-1L Inhibits Hypoxia-Induced Cell Apoptosis through Induction of Mitophagy

Lijun Sun,Yuewen Hao,Rui An,Haixun Li,Cong Xi,Guohong Shen 한국분자세포생물학회 2014 Molecules and cells Vol.37 No.11

Mitophagy, a cellular process that selectively targets dysfunctional mitochondria for degradation, is currently a hot topic in research into the pathogenesis and treatment of many human diseases. Considering that hypoxia causes mitochondrial dysfunction, which results in cell death, we speculated that selective activation of mitophagy might promote cell survival under hypoxic conditions. In the present study, we introduced the Regulator of calcineurin 1-1L (Rcan1-1L) to initiate the mitophagy pathway and aimed to evaluate the effect of Rcan1-1L-induced mitophagy on cell survival under hypoxic conditions. Recombinant adenovirus vectors carrying Rcan1-1L were transfected into human umbilical vein endothelial cells and human adult cardiac myocytes. Using the 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide MTT assay and Trypan blue exclusion assay, Rcan1-1L overexpression was found to markedly reverse cell growth inhibition induced by hypoxia. Additionally, Rcan1-1L overexpression inhibited cell apoptosis under hypoxic conditions, as detected by annexin V-fluorescein isothiocyanate (FITC)/propidium iodide (PI) apoptosis assay. Meanwhile, the mitochondria-mediated cell apoptotic pathway was inhibited by Rcan1-1L. In contrast, knockdown of Rcan1-1L accelerated hypoxia-induced cell apoptosis. Moreover, Rcan1-1L overexpression significantly reduced mitochondrial mass, decreased depolarized mitochondria, and downregulated ATP and reactive oxygen species production. We further delineated that the loss of mitochondrial mass was due to the activation of mitophagy induced by Rcan1-1L. Rcan1-1L overexpression activated autophagy flux and promoted translocation of the specific mitophagy receptor Parkin into mitochondria from the cytosol, whereas inhibition of autophagy flux resulted in the accumulation of Parkin-loaded mitochondria. Finally, we demonstrated that mitochondrial permeability transition pore opening was significantly increased by Rcan1-1L overexpression, which suggested that Rcan1-1L might evoke mitophagy through regulating mitochondrial permeability transition pores. Taken together, we provide evidence that Rcan1-1L overexpression induces mitophagy, which in turn contributes to cell survival under hypoxic conditions, revealing for the first time that Rcan1-1L-induced mitophagy may be used for cardioprotection.

Overexpression of Rcan1-1L Inhibits Hypoxia-Induced Cell Apoptosis through Induction of Mitophagy

Sun, Lijun,Hao, Yuewen,An, Rui,Li, Haixun,Xi, Cong,Shen, Guohong Korean Society for Molecular and Cellular Biology 2014 Molecules and cells Vol.37 No.11

Mitophagy, a cellular process that selectively targets dysfunctional mitochondria for degradation, is currently a hot topic in research into the pathogenesis and treatment of many human diseases. Considering that hypoxia causes mitochondrial dysfunction, which results in cell death, we speculated that selective activation of mitophagy might promote cell survival under hypoxic conditions. In the present study, we introduced the Regulator of calcineurin 1-1L (Rcan1-1L) to initiate the mitophagy pathway and aimed to evaluate the effect of Rcan1-1L-induced mitophagy on cell survival under hypoxic conditions. Recombinant adenovirus vectors carrying Rcan1-1L were transfected into human umbilical vein endothelial cells and human adult cardiac myocytes. Using the 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide MTT assay and Trypan blue exclusion assay, Rcan1-1L overexpression was found to markedly reverse cell growth inhibition induced by hypoxia. Additionally, Rcan1-1L overexpression inhibited cell apoptosis under hypoxic conditions, as detected by annexin V-fluorescein isothiocyanate (FITC)/propidium iodide (PI) apoptosis assay. Meanwhile, the mitochondria-mediated cell apoptotic pathway was inhibited by Rcan1-1L. In contrast, knockdown of Rcan1-1L accelerated hypoxia-induced cell apoptosis. Moreover, Rcan1-1L overexpression significantly reduced mitochondrial mass, decreased depolarized mitochondria, and downregulated ATP and reactive oxygen species production. We further delineated that the loss of mitochondrial mass was due to the activation of mitophagy induced by Rcan1-1L. Rcan1-1L overexpression activated autophagy flux and promoted translocation of the specific mitophagy receptor Parkin into mitochondria from the cytosol, whereas inhibition of autophagy flux resulted in the accumulation of Parkin-loaded mitochondria. Finally, we demonstrated that mitochondrial 1permeability transition pore opening was significantly increased by Rcan1-1L overexpression, which suggested that Rcan1-1L might evoke mitophagy through regulating mitochondrial permeability transition pores. Taken together, we provide evidence that Rcan1-1L overexpression induces mitophagy, which in turn contributes to cell survival under hypoxic conditions, revealing for the first time that Rcan1-1L-induced mitophagy may be used for cardioprotection.

An experimental study on the ballistic performance of FRP-steel plates completely penetrated by a hemispherical-nosed projectile

Changhai Chen,Xi Zhu,Hailiang Hou,Lijun Zhang,Xiaole Shen,Ting Tang 국제구조공학회 2014 Steel and Composite Structures, An International J Vol.16 No.3

Experiments were carried out to investigate the ballistic performance of fiber reinforced plastic(FRP)-steel plates completely penetrated by hemispherical-nosed projectiles at sub-ordnance velocities greater than their ballistic limits. The FRP-steel plate consists of a front FRP laminate and a steel backing plate. Failure mechanisms and impact energy absorptions of FRP-steel plates were analyzed and compared with FRP laminates and single steel plates. The effects of relative thickness, manufacturing method and fabric type of front composite armors as well as the joining style between front composite armors and steel backing plates on the total perforation resistance of FRP-steel plates were explored. It is found that in the case of FRP-steel plates completely penetrated by hemispherical-nosed projectiles at low velocities, the failure modes of front composite armors are slightly changed while for steel backing plates, the dominate failure modes are greatly changed due to the influence of front composite armors. The relative thickness and fabric type of front composite armors as well as the joining style of FRP-steel plates have large effects whereas the manufacturing method of front composite armors has slight effect on the total perforation resistance of FRP-steel plates.

Biodegradation of C5-C8 Fatty Acids and Production of Aroma Volatiles by Myroides sp. ZB35 Isolated from Activated Sludge

Zijun Xiao,Xiankun Zhu,Lijun Xi,Xiaoyuan Hou,Li Fang,Jian R. Lu 한국미생물학회 2014 The journal of microbiology Vol.52 No.5

In the effluents of a biologically treated wastewater from aheavy oil-refining plant, C5-C8 fatty acids including pentanoicacid, hexanoic acid, heptanoic acid, octanoic acid, and2-methylbutanoic acid are often detected. As these residualfatty acids can cause further air and water pollution, a newMyroides isolate ZB35 from activated sludge was explored todegrade these C5-C8 fatty acids in this study. It was foundthat the biodegradation process involved a lag phase thatbecame prolonged with increasing acyl chain length whenthe fatty acids were individually fed to this strain. However,when fed as a mixture, the ones with longer acyl chains werefound to become more quickly assimilated. The branched 2-methylbutanoic acid was always the last one to be depletedamong the five fatty acids under both conditions. Metaboliteanalysis revealed one possible origin of short chain fatty acidsin the biologically treated wastewater. Aroma volatiles including2-methylbutyl isovalerate, isoamyl 2-methylbutanoate,isoamyl isovalerate, and 2-methylbutyl 2-methylbutanoatewere subsequently identified from ZB35 extracts, linking thesource of the fruity odor to these esters excreted by Myroidesspecies. To our best knowledge, this is the first finding of thesearoma esters in bacteria. From a biotechnological viewpoint,this study has revealed the potential of Myroides species asa promising source of aroma esters attractive for food andfragrance industries.

Kinetic modeling of C2–C7 olefins interconversion over ZSM-5 catalyst

Lei Ying,Jiajia Zhu,Youwei Cheng,Lijun Wang,Xi Li 한국공업화학회 2016 Journal of Industrial and Engineering Chemistry Vol.33 No.-

The kinetics of C2–C7 olefins interconversion were studied by feeding individual olefin into industrialZSM-5 catalyst at temperatures of 400–490 8C, space time of 0.0046–0.34 h and partial pressure of13.1 kPa. A kinetic model involving oligomerization, cracking and aromatization of olefins wasestablished. The results showed that the calculated apparent activation energy was negative foroligomerization reactions and positive for cracking reactions. The proposed kinetic model was able topredict the product concentrations in the C2–C7 olefins interconversion over ZSM-5 catalyst, with R2values ranged from 0.969 to 0.996 for the major species.

Hydrogenation of methyl methacrylate under mild conditions using biosynthesis Ru catalyst

Hongling Zhou,Yangqiang Huang,Youwei Cheng,Lijun Wang,Xi Li 한국공업화학회 2017 Journal of Industrial and Engineering Chemistry Vol.47 No.-

Hydrogenation of methyl methacrylate (MMA) was investigated over Ru-based catalyst supported onactive carbons (AC), which was prepared by bio-reduction method, using C. Platycladi (CP) leaf extract asreductant. By varying reaction temperature, hydrogen pressure and reaction time, hydrogenation ofMMA over the biosynthesis Ru-based catalyst was carried out, and resulted the optimum conditions,30 C (room temperature), 2.0 MPa, and 50 min. The as-prepared Ru/AC catalyst showed high catalyticactivity towards the hydrogenation of MMA, affording 100% of MMA conversion even under mildconditions without solvent and methyl isobutyrate was the only product.

Association Between Metabolic Risk Factors and Cognitive Impairment in Schizophrenia Based on Sex

Hongna Huang,Lizhao Du,Zhengping Pu,Yuan Shi,Zifan Xiao,Xi Chen,Shun Yao,Lijun Wang,Zezhi Li,Ting Xue,Donghong Cui 대한신경정신의학회 2023 PSYCHIATRY INVESTIGATION Vol.20 No.10

Objective Sex differences have been observed in many aspects of schizophrenia, including cognitive deficits. Despite extensive research into the relationship between metabolic factors and cognitive deficits in schizophrenia, few studies have explored the potential sex difference in their association. Methods We recruited 358 schizophrenia patients and 231 healthy controls. The participants underwent measurements of body mass index (BMI), waist circumference, blood pressure, triglycerides, high-density lipoprotein cholesterol, and fasting blood glucose. Metabolic risk factors included abdominal obesity, hypertension, hyperglycemia, and dyslipidemia. A collection of these metabolic risk factors has been defined as metabolic syndrome. These diagnoses were based on the criteria of the National Cholesterol Education Program’s Adult Treatment Panel III. Cognitive performance was measured using the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). A descriptive analysis, difference analysis, and linear regression model were used to identify the metabolic risk factors for cognitive function in schizophrenia. Results Our findings revealed sex differences in the rate of abdominal obesity and hypertension in schizophrenic patients. Additionally, we observed sex differences in the association between metabolic risk factors and cognitive impairment in schizophrenia. Specifically, hyperglycemia was associated with the immediate memory index score of RBANS in male patients, while dyslipidemia was associated with language, attention, delayed memory index scores, and RBANS total score in female patients. Conclusion Our results suggest that sex should be considered when evaluating the impact of metabolic disorders on the cognitive function of schizophrenic patients. Moreover, our study identifies hyperglycemia and dyslipidemia as potential targets for precise treatment by sex stratification, which could benefit the improvement of cognitive impairment in schizophrenic patients.