apoptosis-related diseases insufficient apoptosis excessive apoptosis coexistence of insufficient...
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Apoptosis-related DiseasesApoptosis-related DiseasesApoptosis-related DiseasesApoptosis-related Diseases
Insufficient apoptosis Excessive apoptosis Coexistence of insufficient and
excessive apoptosis
Growth Apoptosis
Balance of Growth and ApoptosisBalance of Growth and ApoptosisBalance of Growth and ApoptosisBalance of Growth and Apoptosis
Diseases Mechanism Apoptosis
Heart failure Ischemia, inflammation, etc.
AIDS HIV infection of T4 cell
AD, PD Ischemia, inflammation, etc
Cancer P53, Bcl-2
Autoimmune diseases Autoreactive T cells or B cells
Atherosclerosis Endothelial cell, muscle cell
Apoptosis and DiseasesApoptosis and DiseasesApoptosis and DiseasesApoptosis and Diseases
Gene Affected diseaseTumor necrosis factor Familial periodic fever syndrome receptor 1 (TNF-R1)Fas (CD95; Apo-1) Autoimmune lymphoproliferative syndrome type I(ALPS I), malignant lymphoma, bladder cancerFas ligand Systemic lupus erythematodesPerforin Familial hemophagocytic lymphohistiocytosis (FHL)Caspase 10 Autoimmune lymphoproliferative syndrome type II (ALPS II)
bcl-10 Non-Hodgkin’s lymphomap53 Various malignant neoplasmsBax Colon cancer; hematopoetic malignanciesbcl-2 Non-Hodgkin’s lymphomac-IAP2 Low-grade MALT lymphomaNAIP1 Spinal muscular atrophy
Apoptosis Genes mutated in DiseasesApoptosis Genes mutated in DiseasesApoptosis Genes mutated in DiseasesApoptosis Genes mutated in Diseases
Autoimmune disease,Tumor, virus infection, etc
Proliferation
Apoptosis
Insufficient Apoptosis in DiseasesInsufficient Apoptosis in DiseasesInsufficient Apoptosis in DiseasesInsufficient Apoptosis in Diseases
(1) Tumor Pathogenesis for tumor:
stimulated cell proliferation inhibited cell apoptosis
Cell survival > cell death in diseased tissue Cell apoptosis is actually one of the natural anti-
carcinogenic mechanisms
Signaling Pathways Involved in Apoptosis(Molecules highlighted in red have been found mutated in tumor cells)
Tumor----P53 mutation
ChemicalsVirusRadiation
(2) Autoimmune diseases
The lesion is caused by attack of auto-antibody or sensitized T cell to self-antigen.
Normally, T cells against auto-antigen are eliminated by apoptosis during the development.
When the negative selection is deregulated
(thymus diseases), T cells survive and abnormally proliferate, then attack self tissue, lead to autoimmune diseases.
Mechanism of autoimmune diseases — Disrupted apoptosis of self-reactive cell
Point mutation of FasL
Insertion mutation of Fas
Structural abnormity of FasL
Decreased expression of Fas protein
Escape the negative selection of self-reactive
T cells
Autoimmune diseases
Rheumatoid arthritis
It is caused by decreased apoptosis and increased proliferation of arthral cell ;
Increased IL-1 and TGF-β1 and decreased Fas expression, which inhibit apoptosis;
Increased Bcl-2 、 Bcl-XL, which increased the threshold of apoptosis;
Resistance of T-cells to apoptosis.
AIDS, neurodegenerative diseases, aberrant myocardial ischemic-reperfusion
Excessive Apoptosis in DiseasesExcessive Apoptosis in DiseasesExcessive Apoptosis in DiseasesExcessive Apoptosis in Diseases
( 1 ) Acquired Immune Deficiency Syndrome —AIDS
HIV infection increased Fas gene expression
gp120glycoprotein expression + receptor in CD4 lymphocyte
infusion of infected CD4 cell leads to syncytin formation
produce tat protein (enhance Fas expression) secret TNF
CD+4T- lymphocyte apoptosis
AIDS
(2) Cardiovascular diseases
Cell death induced by ischemia-reperfusion Apoptosis Necrosis Early stage Later stage Peripheral region of infarct Center of infarct Mild ischemia Severe ischemia Chronic Acute
Possible mechanism (myocardial cell apoptosis induced by ischemia-reperfusion):
(1) oxidative stress; (2) calcium overload; (3) p53 gene activation;
(4) death receptor Fas, TNF over expressed.
Heart failure: Myocardial cell diminishes in pressure-
overload-induced heart failure
Possible mechanisms: Oxidative stress; cytokines; ischemia; hypoxia; pressure or volume overload, neural-endocrine system deregulation;
Lead to myocardial cell apoptosis
Alzheimer disease , Parkinson disease , Huntington disease , multiple sclerosis
Factors involved in neuronal apoptosis:
amyloid peptide, calcium overload,
oxidative stress, neuronal growth factor insufficiency,
etc.
Lead to neuronal cell apoptosis
( 3 ) Neurodegenerative diseases
oxidative LDL
platelet activation Ang Ⅱ
hypertension
excess apoptosis insufficiency in in endothelium smooth muscle
atherosclerosis
Coexistence of Excessive and Coexistence of Excessive and Insufficient Apoptosis in DiseasesInsufficient Apoptosis in Diseases
Coexistence of Excessive and Coexistence of Excessive and Insufficient Apoptosis in DiseasesInsufficient Apoptosis in Diseases
Prevention and Therapeutic Potential of Apoptosis
•Interfere signal transduction, signal molecules, receptors, 2nd messengers, etc •Regulate apoptosis-related enzymes and genes •Prevent decrease in mitochondria trans-membrane potential •Others
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