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Lectures in University of Brawijaya, 2013 Biological Responses to Environmental Stress

Lectures in University of Brawijaya, 2013 Biological Responses to Environmental Stress Tetsuro Ishii, PhD. Professor Emeritus, University of Tsukuba, Japan. Animals have developed defense system against environmental stress agents. Plant. Animal. poisons. Detoxification system

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Lectures in University of Brawijaya, 2013 Biological Responses to Environmental Stress

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  1. Lectures in University of Brawijaya, 2013 Biological Responses to Environmental Stress Tetsuro Ishii, PhD. Professor Emeritus, University of Tsukuba, Japan

  2. Animals have developed defense system against environmental stress agents Plant Animal poisons Detoxification system Natural immunity Repair system Apoptosis Toxic agents UV, As, Heavy metals Infection Bacteria, Virus

  3. Stress causes upregulation of stress proteins Detection by sensors stressor Cell damages Activation of transcription factors Heat shock Oxidative stress HSFs Nrf2 Acquire tolerance Gene activation Protein synthesis Repair damages

  4. Biological Responses to Environmental Stress 1. Cellular response to heat 2. Cellular response to electrophiles and reactive oxygen species 3. Nrf2 target genes

  5. Heat was necessary to create life Hydrothermal vent Yellowstone hot spring Adaptation to heat is most important for life.

  6. Heat shock induces various proteins in cells Temperature shift 43°C 37°C Activation of heat shock factors Induction of heat shock proteins (HSPs) Has60, Hsp70, Hsp90, etc.

  7. Heat shock protein (HSP) family HSP110 HSP100 HSP90 HSP70 (DNAK) HSP60 (chaperonin, GroEL) HSP47 HSP40 (DNAJ) HSP33 HSP27 HSP15 HSP10 Some of these proteins are constitutively expressed and play their roles under normal temperature.

  8. Some proteins return to native form following heat denaturation denature or unfolding Renature or refolding But, many proteins became aggregated when denatured

  9. Denatured/unfolded proteins tend to aggregate Protein aggregates

  10. Inhibition of protein aggregation by Dank-ClpB Heat shock Aggregation Native form

  11. Chaperonin inhibits protein aggregation albumin Native form Urea + DTT Denatured form Enzyme activity turbidity ± chaperonin

  12. ATP-dependent folding of GFP-protein by chaperonin GFP fluorescence Time (min) (-) chaperonin Inhibition of protein aggregate by chaperonin Opitical Scattering (+) chaperonin Time (min)

  13. Chaperonin inhibits protein aggregate by heat treatment Without chaperonin With chaperonin

  14. Double ring structure of chaperonin, GroEL

  15. GroEL-GroES complex provides space for protein folding

  16. Discovery of chaperonin “Molecular chaperon” was found in different systems

  17. Functions of chaperonin during protein synthesis Protein synthesis hsp Miss-folding chaperonin aggregates normal folding

  18. Role of chaperons in protein synthesis

  19. Role of chaperons in protein targeting to mitochondria

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