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HCV ALTERS POLYAMINE METABOLISM IN HUH7 CELLS

Engelhardt Institute of Molecular Biology Russian Academy of Sciences. HCV ALTERS POLYAMINE METABOLISM IN HUH7 CELLS. Olga Smirnova, Tuomo Keinanen , Mervi Hyvonen , Inna Karpenko , Vera Tunitskaya , Maria Isaguliants, Sergey Kochetkov, Alexander Ivanov.

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HCV ALTERS POLYAMINE METABOLISM IN HUH7 CELLS

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  1. Engelhardt Institute of Molecular Biology Russian Academy of Sciences HCV ALTERS POLYAMINE METABOLISM IN HUH7 CELLS Olga Smirnova, TuomoKeinanen, MerviHyvonen, Inna Karpenko, Vera Tunitskaya, Maria Isaguliants, Sergey Kochetkov, Alexander Ivanov

  2. Principles of polyamine metabolism Nrf2

  3. Questions 1. What happens to the polyamine metabolism in Huh7 cells under oxidative stress?

  4. Oxidative stress triggers an increase in polyamine levels by activating the transcription of ODC over to the transcription of SSAT in Huh7 cells

  5. Oxidative stress activates transcription of both SSAT and ODC via Nrf2 and NF-kB ROS Nrf2 NF-kB ODC SSAT Increase in the levels of polyamines

  6. Questions 1. What happens to the polyamine metabolism in Huh7 cells under oxidative stress? • Polyamine levels: strong increase • Enzymes: elevated ODC and SSAT levels 2. What happens to the polyamine metabolism during Transient expression of HCV proteins?

  7. Transient expression of the core and NS5A proteins activated transcription of SSAT and ODC genes ODC SSAT

  8. Expression of the core and NS5A proteins results in elevation of putrescine level… …not accompanied by increase in the intracellular ODC activity

  9. Questions 1. What happens to the polyamine metabolism in Huh7 cells under oxidative stress? • Polyamine levels: strong increase • Enzymes: elevated ODC and SSAT levels 2. What happens to the polyamine metabolism during Transient expression of HCV proteins? • Polyamine levels: moderate elevation of putrescine level • Enzymes: suppressed ODC expression 2. Are there differences in polyamine metabolism between transient and long-term expression of HCV proteins?

  10. In Huh7 cells harboring HCV replicon there is no pronounced activation of transcription of polyamine-metabolizing enzymes… … and other Nrf2-dependent genes

  11. Acknowledgements Sergey Kochetkov lab (EIMB)KarolinskaInstitutet (Sweden) Alex Ivanov Inna Karpenko Vera Tunitskaya Maria Isaguliants Alexey Khomutov A.I. Virtanen Institute (Finland) TuomoKeinänen MerviHyvonen The project was supported by: • Russian Foundation for Basic Research • Grant of President of Russian Federation

  12. THANK YOU FOR YOUR ATTENTION

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