Volume 45 Issue 2
Feb.  2024
Turn off MathJax
Article Contents
Jinling XIAO, Yaling GUAN, Sensen ZHU, Mengjie ZHUANG, Liping SU, Hongwei PU. Role of HK2 and VDAC1 in Diacetylmorphine-induced Cardiomyocyte Apoptosis[J]. Journal of Kunming Medical University, 2024, 45(2): 7-13. doi: 10.12259/j.issn.2095-610X.S20240202
Citation: Jinling XIAO, Yaling GUAN, Sensen ZHU, Mengjie ZHUANG, Liping SU, Hongwei PU. Role of HK2 and VDAC1 in Diacetylmorphine-induced Cardiomyocyte Apoptosis[J]. Journal of Kunming Medical University, 2024, 45(2): 7-13. doi: 10.12259/j.issn.2095-610X.S20240202

Role of HK2 and VDAC1 in Diacetylmorphine-induced Cardiomyocyte Apoptosis

doi: 10.12259/j.issn.2095-610X.S20240202
  • Received Date: 2023-11-29
    Available Online: 2024-02-27
  • Publish Date: 2024-02-25
  •   Objective  To investigate the role of HK2 and VDAC1 in diacetylmorphine-induced cardiomyocyte apoptosis.   Methods  A dose-escalation method was used to establish a rat model of diacetylmorphine addiction. Forty SD rats were randomly divided into three groups, the normal group (n=10) was injected with an equal amount of saline subcutaneously, the model group (n=15) was injected with 5 mg/kg of diacetylmorphine for the first time, and then the dose was increased by 2.5 mg/ (kg·d) day by day for 20 days, and the group of model + 10 D (n=15) continued to increase the dose based on the model group up to the 10th day. Lactate dehydrogenase (LDH) and glutamic oxaloacetic transaminase (GOT) were detected by ELISA; HE staining was used to observe the pathological changes of myocardial tissues in each group; TUNEL staining was used to detect apoptosis in myocardial tissues in each group; and immunohistochemistry, RT-q-analysis, and immunochemistry were used to detect apoptosis in myocardial tissues in each group. Immunohistochemistry, RT-qPCR and Western blot were used to detect the mRNA and protein expression of HK2, VDAC1 and apoptosis-related factors.   Results  HE staining revealed that myocardial tissues exhibited different degrees of damage with the prolongation of diacetylmorphine intervention. Compared with the normal group, serum LDH, GOT content and myocardial apoptosis rate increased in the model group, mRNA and protein levels of HK2 and anti-apoptotic factor Bcl-2 decreased, mRNA and protein levels of VDAC1 and pro-apoptotic factors Bax and Caspase-3 increased, and the protein level of Clevead Caspase-3 increased; in the model + 10 D group the above indexes, there was a statistically significant difference (P < 0.05).   Conclusion  Diacetylmorphine can cause cardiomyocyte apoptosis, and VDAC1 may be involved in the process of cardiomyocyte apoptosis caused by diacetylmorphine.
  • loading
  • [1]
    Milella M S,D'Ottavio G,De Pirro S,et al. Heroin and its metabolites: relevance to heroin use disorder[J]. Transl Psychiatry,2023,13(1):120. doi: 10.1038/s41398-023-02406-5
    [2]
    王珺,李光伟,汪娜,等. Kelch样ECH相关蛋白1/核因子E2相关因子2对2型糖尿病心肌细胞凋亡的影响[J]. 中国临床药理学杂志,2023,39(5):635-638.
    [3]
    刘小山,陈玉川,李朝晖,等. 海洛因成瘾大鼠心电图及心肌超微结构改变的研究[J]. 法医学杂志,2004,20(3):129-132,135.
    [4]
    Ciscato F,Ferrone L,Masgras I,et al. Hexokinase 2 in cancer: A prima donna playing multiple characters[J]. Int J Mol Sci,2021,22(9):4716. doi: 10.3390/ijms22094716
    [5]
    Bao C,Zhu S,Song K,et al. HK2: A potential regulator of osteoarthritis via glycolytic and non-glycolytic pathways[J]. Cell Commun Signal.,2022,20(1):132. doi: 10.1186/s12964-022-00943-y
    [6]
    Shoshan-Barmatz V,Maldonado E N,Krelin Y. VDAC1 at the crossroads of cell metabolism,apoptosis and cell stress[J]. Cell Stress,2017,1(1):11-36. doi: 10.15698/cst2017.10.104
    [7]
    周晓昕,张玉静,肖芳,等. 六价铬诱导的肝细胞线粒体依赖性凋亡中VDAC1的作用[J]. 生态毒理学报,2017,12(6):91-98.
    [8]
    Fan K,Fan Z,Cheng H,et al. Hexokinase 2 dimerization and interaction with voltage-dependent anion channel promoted resistance to cell apoptosis induced by gemcitabine in pancreatic cancer[J]. Cancer Med,2019,8(13):5903-5915. doi: 10.1002/cam4.2463
    [9]
    Ji M,Su L,Liu L,et al. CaMKII regulates the proteins TPM1 and MYOM2 and promotes diacetylmorphine-induced abnormal cardiac rhythms[J]. Sci Rep,2023,13(1):5827. doi: 10.1038/s41598-023-32941-6
    [10]
    Rosen D,Smith M L,Reynolds C F 3rd. The prevalence of mental and physical health disorders among older methadone patients[J]. Am J Geriatr Psychiatry,2008,16(6):488-497. doi: 10.1097/JGP.0b013e31816ff35a
    [11]
    杜磊,夏海发,吴映辉,等. 吗啡对急性心肌缺血大鼠的作用及机制研究[J]. 中国临床药理学杂志,2021,37(18):2451-2455.
    [12]
    Xi H,Wang S,Wang B,et al. The role of interaction between autophagy and apoptosis in tumorigenesis (Review)[J]. Oncol Rep,2022,48(6):208.
    [13]
    苟陶然,李重阳,欧锐,等. 海洛因对小鼠视网膜结构和抗氧化物酶的影响[J]. 解剖学报,2017,48(6):663-668.
    [14]
    Bernstein H G,Trübner K,Krebs P,et al. Increased densities of nitric oxide synthase expressing neurons in the temporal cortex and the hypothalamic paraventricular nucleus of polytoxicomanic heroin overdose victims: possible implications for heroin neurotoxicity[J]. Acta Histochem,2014,116(1):182-190. doi: 10.1016/j.acthis.2013.07.006
    [15]
    刘小山,刘水平,李朝晖,等. 海洛因成瘾大鼠心肌超微结构改变及凋亡检测[J]. 中山大学学报(医学科学版),2005,26(1):61-64,83.
    [16]
    Roberts D J,Miyamoto S. Hexokinase II integrates energy metabolism and cellular protection: Akting on mitochondria and TORCing to autophagy [published correction appears in cell death differ. 2015 Feb;22(2): 364][J]. Cell Death Differ,2015,22(2):248-257. doi: 10.1038/cdd.2014.173
    [17]
    Song G,Lu Q,Fan H,et al. Inhibition of hexokinases holds potential as treatment strategy for rheumatoid arthritis[J]. Arthritis Res Ther,2019,21(1):87. doi: 10.1186/s13075-019-1865-3
    [18]
    Kim K W,Kim S W,Lim S,et al. Neutralization of hexokinase 2-targeting miRNA attenuates the oxidative stress-induced cardiomyocyte apoptosis[J]. Clin Hemorheol Microcirc,2021,78(1):57-68. doi: 10.3233/CH-200924
    [19]
    Shoshan-Barmatz V,Shteinfer-Kuzmine A,Verma A. VDAC1 at the intersection of cell metabolism,apoptosis,and diseases[J]. Biomolecules,2020,10(11):1485. doi: 10.3390/biom10111485
    [20]
    Shoshan-Barmatz V,Nahon-Crystal E,Shteinfer-Kuzmine A,Gupta R. VDAC1,mitochondrial dysfunction,and Alzheimer’s disease[J]. Pharmacol Res,2018,131:87-101. doi: 10.1016/j.phrs.2018.03.010
    [21]
    宋阿北. VDAC1参与调控BCG感染的巨噬细胞凋亡的机制研究[D]. 银川: 宁夏大学, 2021.
    [22]
    Li Y,Kang J,Fu J,et al. PGC1α Promotes cisplatin resistance in ovarian cancer by regulating the HSP70/HK2/VDAC1 signaling pathway[J]. Int J Mol Sci,2021,22(5):2537. doi: 10.3390/ijms22052537
    [23]
    Yuan S,Fu Y,Wang X,et al. Voltage-dependent anion channel 1 is involved in endostatin-induced endothelial cell apoptosis[J]. FASEB J,2008,22(8):2809-2820. doi: 10.1096/fj.08-107417
    [24]
    Shoshan-Barmatz V,Ben-Hail D,Admoni L,et al. The mitochondrial voltage-dependent anion channel 1 in tumor cells[J]. Biochim Biophys Acta,2015,1848(10 Pt B):2547-2575.
  • Relative Articles

    [1] Yuyun YOU, Yunfei HONG, Xia ZHENG, Feifei LIU, Jinsong YIN. The Association between Serum Homocysteine to High-Density Lipoprotein Cholesterol Ratio and Premature Coronary Heart Disease. Journal of Kunming Medical University, 2025, 46(4): 1-7.
    [2] Weihua ZHANG, Shanshan QIN, Sicong WEN, Pingyu WU, Zhaoguang SONG. The Mechanism of Acetylcysteine Aerosol Inhalation Combined with Non-invasive Ventilator NIPSV Mode in the Treatment of AECOPD with Respiratory Failure by Regulating Immune Inflammatory Response. Journal of Kunming Medical University, 2024, 45(7): 113-118.  doi: 10.12259/j.issn.2095-610X.S20240717
    [3] Ji WANG, Songtao BIN, Li TAN. Study on the Efficacy of Acetylcysteine in Severe Pneumonia in Children under Electronic Bronchoscopy. Journal of Kunming Medical University, 2024, 45(6): 113-119.  doi: 10.12259/j.issn.2095-610X.S20240615
    [4] Jun-jie LI, Hai-yan JIANG, Wen-ya BAI, Si-ying HUO, Zhi-sheng SUN, Jian-lin SHAO. Effects of Silencing RND3 Expression on the Inflammatory Response and Apoptosis of Hippocampal Neurons Injured by Oxygen Glucose Deprivation/Reoxygenation. Journal of Kunming Medical University, 2021, 42(10): 14-21.  doi: 10.12259/j.issn.2095-610X.S20211012
    [5] Hai-ping ZHANG, Shu-juan YANG, Li-xia YANG, Zhao-juan RUAN, Rui-wei GUO. Effect of Hyperhomocysteinemia on Cardiac Function and Mortality of Patients with Acute Myocardial Infarction Concomitant Hypertension underwent Primary Percutaneous Coronary Intervention after 6 Months. Journal of Kunming Medical University, 2021, 42(3): 73-78.  doi: 10.12259/j.issn.2095-610X.S20210319
    [6] Li Jian Jiao , Dai Xiao Ming . A Study on Expression of Histone Deacetylase-2 in Humantongue Squamous Cell Carcinomas. Journal of Kunming Medical University, 2018, 39(08): 80-85.
    [7] Hou Yun He , Zhang Hao Xin , Wang Yi Yu , Su Yan Mei , Gu Dan Shan , Lin Shao Fang , Yang Shi Kun , Li Shu De . Regulatory Mechanism of Ginsenoside Rg1 on Homocysteine in NAFLD Model. Journal of Kunming Medical University, 2018, 39(04): 27-33.
    [8] Zhang Mei . The Effect of High Homocysteine on Blood Glucose Control in Type 2 Diabetic Patients. Journal of Kunming Medical University,
    [9] Deng Yong Qian . . Journal of Kunming Medical University, 2015, 36(09): 1-1.
    [10] Shen Yue Ling . . Journal of Kunming Medical University,
    [11] Huang Xiao Bin . . Journal of Kunming Medical University,
    [12] Lin Yan . . Journal of Kunming Medical University,
    [13] Chai Yan Jing . . Journal of Kunming Medical University,
    [14] Ling Da Qing . . Journal of Kunming Medical University,
    [15] Tao Hong Fei . . Journal of Kunming Medical University,
    [16] Gu Yu . Effect of Homocysteine on PDK1 in Skeletal Muscle Tissue of Mic. Journal of Kunming Medical University,
    [17] . . Journal of Kunming Medical University,
    [18] . TRB3 Mediates Homocysteine-induced Inhibition of Endothelial Cells Proliferation. Journal of Kunming Medical University,
    [19] . 2D-QSAR Studies on Flavonoids as Inhibitors of Recombinant Human Protein Kinase CK2 Holoenzyme. Journal of Kunming Medical University,
    [20] . Association between Serum Homocyteine and Coronary Arteriosclerosis. Journal of Kunming Medical University,
  • 加载中

Catalog

    通讯作者: 陈斌, bchen63@163.com
    • 1. 

      沈阳化工大学材料科学与工程学院 沈阳 110142

    1. 本站搜索
    2. 百度学术搜索
    3. 万方数据库搜索
    4. CNKI搜索

    Figures(6)  / Tables(1)

    Article Metrics

    Article views (812) PDF downloads(16) Cited by()
    Proportional views
    Related

    /

    DownLoad:  Full-Size Img  PowerPoint
    Return
    Return