Involvement of adenosine kinase in the phosphorylation of formycin B in CHO cells |
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| Authors: | K D Mehta R S Gupta |
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| Institution: | 1. Department of Geography, Patna University, Bihar, India;2. Department of Geography & Regional Development, University of Kashmir, Srinagar, India;1. Department of Immunology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China;2. Department of Clinical Laboratory, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China;3. Prenatal Diagnosis Center, Guangdong Provincial Emergency Hospital, Guangdong Second Provincial General Hospital, Guangzhou, China;4. Department of Laboratory Medicine, The Second Affiliated Hospital of Guilin Medical University, Guilin, China;5. Department of Dermatology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China;6. Department of Rheumatology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China;7. Department of Immunology and Microbiology, Shanghai Institute of Immunology, Shanghai Jiao Tong University School of Medicine, Shanghai Jiao Tong University, Shanghai, China;8. Department of Urology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China;9. The Key Laboratory of Stem Cell Biology, Institute of Health Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences and Shanghai Jiao Tong University School of Medicine, Shanghai, China;10. Key Laboratory of Organ Transplantation, Ministry of Education, Wuhan, China;11. NHC Key Laboratory of Organ Transplantation, Wuhan, China;12. Key Laboratory of Organ Transplantation, Chinese Academy of Medical Sciences, Wuhan, China |
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| Abstract: | In Chinese hamster ovary cells, 3H]formycin B is metabolized into formycin B-5'-monophosphate, formycin A-5'-monophosphate and higher phosphorylated derivatives of formycin A which are incorporated into RNA. Mutants of CHO cells independently selected for resistance to various adenosine analogs viz. toyocamycin, tubercidin, 6-methylmercaptopurine riboside, which contain no detectable activity of adenosine kinase (AK) in cell extracts, all exhibited between 2- to 3-fold increased resistance to formycin B. Formycin B-resistant mutants of CHO cells are also affected in AK, as indicated by the absence of AK activity in cell extracts. Both types of AK- mutants showed reduced uptake and phosphorylation of 3H]formycin B in comparison to the parental (AK+) cells. In addition, toxicity of formycin B towards CHO cells was reduced in presence of adenosine in a concentration dependent manner. These observations strongly indicate that in CHO cells, formycin B is phosphorylated via AK and that like other nucleoside analogs its phosphorylation may be essential for the drugs cellular toxicity. |
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