Diabetic NephropathyCancer / Angiogenesis

Alzheimer’s

Cardiovascular Disease

COPD NeurohormonalStress / Depression

MembraneDamage

LocalizedCell

Death

JNKPathway

Activation

CalpainCaspase3

p35

p25

CDK5

CT26 CT31

C-TerminalFragments

(CTFs)

Tau Phosphorylation

NeurofibrillaryTangles (NFTs)

MicrotubuleDestabilization

GSK-3βMAPK

PathwayActivation

NitricOxide

ROS

Microglial Activation +Inflammatory Response

sAPPα

sAPPβ

α

α Secretase

APP

β/γ Secretases

γ β

AmyloidPlaque

Formation

AmyeloidPrecursor

Protein(APP)

Aβ40

Aβ42

Ca2+

Fas-L

Aβ

c-Jun c-Fos

Fas-L

RAS

RAF

MEK

ERK

SHC GRB2

SOS

PYK2

SRC

PLC-γ

STAT3 STAT1DAG

DAG

FYN

Growth FactorReceptors Angiotensin II

AdvancedGlycation

End-Products

SHP-2JAK2

ElectronTransport

SHP-1

ROS

STAT3 STAT1ELK1

c-Fosc-Jun

TGF-βPARP

Fructose

GAPDH

PLD2

PKC

NADPH

NOX

GP91RACp22

p67 p47

ROS

NADP+

TGF-β

Glucose

GLUT4

Glucose

Autooxidation

AldoseReductase

SorbitolPolyol

PathwaySorbitolDehydrogenase

NADHNAD+

DAGPyruvic

AcidGlycolysis

Ca2+

GaqAT1R

Glomerularsclerosis

GlomerularMesangial

Cell Growth

Collagen IV

RAGE

RAS

RAF

MEK

ERK

VEGF

Proteasome

Ubiquitination

p53Degradation

eNOS

NitricOxide

Ca2+

IP3

PLCγ

GrowthSignaling

VEGF-R

SHC GRB2

SOS

PI3K

AKT

XIAP

14-3-3

BAD

BclXLApoptosis

RSKVHL

HuR

HypoxiaRadiation

ATM

CK-1

MDM2

p53

MDM2

p53

NuclearImport

Thr18

Ser15

p53 mSin3A

p53 p300MDM2

VEGF mRNAStabilization

HIF-1α ARNT

VEGF

Radiation

DNA Damage

GROWTH ARREST GENESBAXp21

PARP-1

InflammatoryGene ExpressionIL-6TNFαMucin Production

IL-1βiNOS

ROS

Hypoxia-inducedVEGF Production

NatriureticPeptides

(NP)

ParticulateGC

PDE

SolubleGC PKG PKA

Ca2+

cGMP

PDEs

cAMP

MultipleTargets

NO

iNOS HO-1

ROS

CO

Nitric Oxide

CarbonMonoxide

H2O2

SOD

O2-

ONOO-

Peroxynitrite

Loss ofMitochondrial

MembranePotential

CaspaseActivation

AIF

EndoG

CytC

AIF

EndoG

DY

L-Arginine

COX-I/II

AA PGG2

PGH2

TXA2

LipidPeroxidation

TXA2

Vasoconstriction

DNAFragmentation

O2-

Superoxide

AKT

PI3K

ROS

GSH GSSG

MKKASK1

p38MAPK

JNK

MultiplePathway

Activation

GlutathioneOxidation/Reduction

GPX

GR

PGH2

PGE2Synthase

PGE2

PGG2

COX I/II

AA

PGE2

Inflammation-InducedLipid Peroxidation

8-iso-PGF2α EGFR

RAS

RAF

MEK

ERK

ROS

PKC

MSK-1

Keap-1

Nrf2

Nrf2 c-Fos

c-Jun

SODHO-1

RAP-1

PKA

cAMP

EP2/4

Gas AC

CREB NFκB

RSK

CREB

CREB

PKA ERK

MEK

cAMPβ-catenin

GSK-3

HRE Genes

GR

GR

GR

GR

c

c

c

c

c

c

EnhancedNeuroplasticity

NuclearImport

Bcl-2

BAD

AKTRAF

AKT

DSHV

AC

B2AR

Wnt

PI3K

IP3

Hsp90IM

GlucocorticoidReceptorActivation

RAS

SOS

Stress

BDNF

TrkB

PIP2

DAG

ACTH

Glucocorticoids(e.g. Cortisol)

CorticotropinReleasing Hormone

HPA AxisActivation

Norepinepherine

Gas

Fz

TrkBBDNF

Bcl-2

PhosphodiesteraseInhibitor

AntidepressantsPhosphorylation

BAD

RAS

RAF

MEK

ERK

Disease-Associated Stress Signaling

ProteinsNAME

NAME Transcription Factors

Inhibition

Gene Activation

Activation

Favored

Many key signaling pathways determine whether cells are able to maintain homeostasis upon temporary or persistent exposure to stress. A variety of stressors including infl ammation, an imbalance in nutrients, lack of oxygen (hypoxia), or improper folding of proteins, contribute to dysregualtion of critical pathways, ultimately resulting in disease. Enzo Life Sciences products are used by researchers around the world to investigate cellular stress signaling pathways involved in diabetes, cancer, cardiovascular disease, chronic obstructive pulmonary disease (COPD), Alzheimer’s disease and depression.

ZZ-W

0610

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1

8-iso prostaglandin F2α

Arachidonic acidAdenylyl cyclaseAdrenocorticotropic hormoneApoptosis-inducing factorAmyloid precursor proteinAryl hydrocarbon receptor nuclear translocatorAtaxia telangiectasia-mutated geneAmyloid betaBeta 2 adrenergic receptorBcl2-antagonist of cell deathB-cell lymphoma protein 2Brain derived neurotrophic factorcyclic adenosine monophosphateCyclin dependent kinaseCyclic guanosine monophosphateCyclooxygenaseCyclic AMP response element bindingC-terminalCytochrome CDiacylglycerolDisheveledEpidermal growth factor receptorEndonuclease G

Endothelial nitric oxide synthaseProstaglandin receptorsFrizzled receptorGlyceraldehyde 3-phosphate dehyrogenaseGuanylyl cyclaseGlucose transporter 4Glutathione peroxidaseGlucocorticoid receptor (Neurohormonal Stress)Glutathione reductase (COPD)Reduced glutathioneGycogen synthase kinaseGlutathione disulfi deHydrogen peroxideHypoxia inducible factorHeme oxygenase-1Hypothalamus pituitary adrenalHormone response elementHeat shock proteinHu antigen R ImmunophilinInducible nitric oxide synthaseInositol triphosphateKelch-like ECH-associated protein 1Mouse double minute 2 homolog

Nuclear factor κ-light-chain-enhancer of activated B cellsNADPH oxidaseNF-E2-related factor 2PhosphodiesteraseProstaglandin E2

Prostaglandin G2

Prostaglandin H2

Phosphoinositide 3-kinasePhosphatidyl inositol bisphosphateProtein kinase AProtein kinase CProtein kinase GPhospholipase D2

Reactive oxygen speciesSuperoxide dismutaseSignal transducer and activator of transcriptionTransforming growth factor betaTyrosine receptor kinase BThromboxane A2

Vascular endothelial growth factorvon Hippel-Lindau tumor suppressorX-linked inhibitor of apoptosis

8-iso-PGF2α

AAACACTHAIFAPPARNTATMAβB2ARBADBcl-2BDNFcAMP CDKcGMPCOX CREBCTCytCDAGDSHVEGFREndoG

eNOSEP2/4

FzGAPDHGCGLUT4GPXGRGRGSHGSKGSSGH2O2

HIF-1HO-1HPAHRE HspHuRIMiNOSIP3

Keap-1MDM2

NFκBNOXNrf2PDE PGE2

PGG2

PGH2

PI3KPIP2

PKAPKCPKGPLD2

ROSSODSTATTGF-βTrkBTXA2

VEGFVHLXIAP

Abbreviations