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Hydroxysafflower yellow A alleviates HK-2 cells injury in cold hypoxia/reoxygenation via mitochondrial apoptosis
Institution:1. Key Laboratory of Functional and Clinical Translational Medicine, Fujian Province University, Xiamen Medical College, Xiamen, Fujian 361023,China;2. Department of Basic Medicine, Xiamen Medical College, Xiamen, Fujian 361023, China;3. The Second Affiliated Hospital of Xiamen Medical College, Xiamen, Fujian 361023, China;4. Medical College of Xiamen University, Xiamen, Fujian 361100, China;1. Xenotransplantation Program, Department of Surgery, University of Alabama at Birmingham, Birmingham, AL, USA;2. Division of Cardiothoracic Surgery, Department of Surgery, University of Alabama at Birmingham, Birmingham, AL, USA;3. Revivicor, Blacksburg, VA, USA;4. Department of Pediatric Cardiology, Division of Critical Care, University of Alabama at Birmingham, Birmingham, AL, USA;1. Transfusion Medicine & Blood Centre, Jaypee Hospital, Noida, Delhi NCR, India;2. Nephrology & Renal Transplant, Jaypee Hospital, Noida, Delhi NCR, India;3. Urology & Renal Transplant, Jaypee Hospital, Noida, Delhi NCR, India;1. Medical Research Center, Affiliated Hospital of Jining Medical University, Jining, PR China;2. Institute of Immunology and Molecular Medicine, Jining Medical University, Jining, PR China;3. Department of Infectious Disease, Qingdao Municipal Hospital, Qingdao, PR China;4. Jilin University No 3 Hospital, Jilin, PR China;5. Shanghai Meifeng Biotechnology Co., Ltd, Shanghai, PR China;6. Institute of Liver Diseases, Affiliated Hospital of Jining Medical University, Jining, PR China
Abstract:Cold storage for organ preservation in kidney transplantation is a core predisposing factor for delayed graft function and the long-term outcome of transplanted kidneys. Hydroxysafflor yellow A (HSYA) is the most effective water-soluble active monomer in Safflower with a strong property of inhibiting hypoxia and reoxygenation (H/R). However, the evidence concerning the effect of HSYA on H/R in kidney transplantation is limited. To investigate whether HSYA has a protective effect on cold H/R injury,we investigated the possible protective mechanism. Here, we incubated HK-2 cells to establish a cold H/R model and observed HSYA activation in an in vitro model of cold-storage rewarming which included the cell survival rate, cell morphology and ultrastructure, protein expression of Bcl-2, Bax, Cytsingle bondC, Apaf-1, and caspase-3, and status of mitochondrial permeability transformation pores (MPTPs). Our data showed that HSYA pretreatment increased the survival rate of the cells, alleviated mitochondrial damage, decreased the expression of apoptosis-related proteins and inhibited the openness of mitochondrial permeability transformation pores. Our findings suggested that HSYA may be a major predisposing mediator of mitochondrial apoptosis and renal tubular injury in cold storage–associated transplantation and may be an effective therapeutic target for improving graft function and graft survival.
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