Eimre Margus, Paju Kalju, Pelloux Sophie, Beraud Nathalie, Roosimaa Mart, Kadaja Lumme, Gruno Marju, Peet Nadezhda, Orlova Ehte, Remmelkoor Reele, Piirsoo Andres, Saks Valdur, Seppet Enn
Department of Pathophysiology, Centre of Molecular and Clinical Medicine, Faculty of Medicine, University of Tartu, Tartu, Estonia.
Biochim Biophys Acta. 2008 Jun;1777(6):514-24. doi: 10.1016/j.bbabio.2008.03.019. Epub 2008 Mar 29.
Expression and function of creatine kinase (CK), adenylate kinase (AK) and hexokinase (HK) isoforms in relation to their roles in regulation of oxidative phosphorylation (OXPHOS) and intracellular energy transfer were assessed in beating (B) and non-beating (NB) cardiac HL-l cell lines and adult rat cardiomyocytes or myocardium. In both types of HL-1 cells, the AK2, CKB, HK1 and HK2 genes were expressed at higher levels than the CKM, CKMT2 and AK1 genes. Contrary to the saponin-permeabilized cardiomyocytes the OXPHOS was coupled to mitochondrial AK and HK but not to mitochondrial CK, and neither direct transfer of adenine nucleotides between CaMgATPases and mitochondria nor functional coupling between CK-MM and CaMgATPases was observed in permeabilized HL-1 cells. The HL-1 cells also exhibited deficient complex I of the respiratory chain. In conclusion, contrary to cardiomyocytes where mitochondria and CaMgATPases are organized into tight complexes which ensure effective energy transfer and feedback signaling between these structures via specialized pathways mediated by CK and AK isoforms and direct adenine nucleotide channeling, these complexes do not exist in HL-1 cells due to less organized energy metabolism.
在搏动(B)和非搏动(NB)的心脏HL-1细胞系以及成年大鼠心肌细胞或心肌组织中,评估了肌酸激酶(CK)、腺苷酸激酶(AK)和己糖激酶(HK)同工型的表达及功能,及其在调节氧化磷酸化(OXPHOS)和细胞内能量转移中的作用。在这两种类型的HL-1细胞中,AK2、CKB、HK1和HK2基因的表达水平均高于CKM、CKMT2和AK1基因。与皂素通透的心肌细胞相反,OXPHOS与线粒体AK和HK偶联,但不与线粒体CK偶联,并且在通透的HL-1细胞中未观察到腺嘌呤核苷酸在CaMgATP酶和线粒体之间的直接转移,也未观察到CK-MM与CaMgATP酶之间的功能偶联。HL-1细胞还表现出呼吸链复合体I缺陷。总之,与心肌细胞不同,在心肌细胞中,线粒体和CaMgATP酶形成紧密复合体,通过由CK和AK同工型介导的特殊途径以及腺嘌呤核苷酸的直接通道作用,确保这些结构之间有效的能量转移和反馈信号传递,但由于能量代谢组织性较差,这些复合体在HL-1细胞中不存在。