Lectures in University of Brawijaya, 2013

Biological Responses to Environmental Stress

Tetsuro Ishii, PhD.Professor Emeritus, University of Tsukuba, Japan

AnimalPlantpoisonsDetoxification systemNatural immunityRepair systemApoptosisAnimals have developed defense system against environmental stress agentsToxic agentsUV, As, Heavy metalsInfectionBacteria, Virus

Stress causes upregulation of stress proteinsstressorDetection by sensorsGene activationProtein synthesisRepair damagesCell damagesAcquire toleranceActivation of transcription factors

Biological Responses to Environmental Stress

1. Cellular response to heat 2. Cellular response to electrophiles and reactive oxygen species 3. Nrf2 target genes

Heat was necessary to create lifeAdaptation to heat is most important for life.Yellowstone hot springHydrothermal vent

Heat shock induces various proteins in cells37C43CTemperature shiftInduction of heat shock proteins (HSPs)Has60, Hsp70, Hsp90, etc.Activation of heat shock factors

Heat shock protein (HSP) familyHSP110HSP100HSP90HSP70 (DNAK)HSP60 (chaperonin, GroEL)HSP47HSP40 (DNAJ)HSP33HSP27HSP15HSP10Some of these proteins are constitutively expressed and play their roles under normal temperature.

Some proteins return to native form following heat denaturationdenature or unfoldingRenature or refoldingBut, many proteins became aggregated when denatured

Denatured/unfolded proteins tend to aggregateProtein aggregates

Inhibition of protein aggregation by Dank-ClpBHeat shockAggregationNative form

Chaperonin inhibits protein aggregationNative formDenatured formUrea + DTT chaperoninalbuminEnzyme activityturbidity

Opitical ScatteringInhibition of protein aggregate by chaperoninATP-dependent folding of GFP-protein by chaperoninGFP fluorescence(+) chaperonin(-) chaperoninTime (min)Time (min)

Without chaperoninWith chaperoninChaperonin inhibits protein aggregate by heat treatment

Double ring structure of chaperonin, GroEL

GroEL-GroES complex provides space for protein folding

Discovery of chaperoninMolecular chaperon was found in different systems

Functions of chaperonin during protein synthesischaperoninhspnormal foldingaggregatesProtein synthesisMiss-folding

Role of chaperons in protein synthesis

Role of chaperons in protein targeting to mitochondria

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