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8 Cards in this Set
- Front
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Structure of cytokine receptors (multisubunit) |
Usually heterodimer alpha: binding cytokine beta (larger intracellular domain): produce intracellular signals |
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Functions of alpha subunit of cytokine receptors |
- Antgonist (soluble, binds with cytokine to prevent its interaction with real cell surface receptor) - Trans-signalling: cytokine complex binds with signal producing beta-subunit expressed in another cell |
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Characteristics of cytokine effects |
1. Pleiotropy: same cytokine produce different effects on different cell types 2. Redundancy: Different cytokine receptors have different alpha but same beta subunit 3. Antagonism: different cytokines with different alpha subunit compete for same beta subunit 4. Synergy: two cytokines enhance each other's effect |
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Difference between the biochemical composition of cytokines and prostaglandins |
Cytokine: Low molecular weight protein Porstaglandin: Synthesized from fatty acid |
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Synthesis of prostaglandins |
Stimulation (e.g. hormones, growth factors) increase expression of cPLA2
Phospholipids --> (phospholipiase A2) --> Arachidonic acid --> (COX) --> Prostaglandin-G --> (peroxidase) --> Prostaglandin H --> various enzymes to produce various prostaglandins |
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Cell-type specific synthesis of prostaglandins form PGH and their funcitons |
1. Platelet - TxA2: Vasoconstriction, platelet aggregation 2. Endothelial cells - PGI2: vasodilation, platelet declumping 3. Uterus - PGF2alpha: uterine endothelial smooth muscle contraction 4. Mast cells - PGD2: Chemotaxis, allergy 5. Most cells - PGE2: pain, fever, ovulation |
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Two forms of COX (PGHS) (location, effect, lipids involved, activity level, |
COX1: - constitutively expressed in all cells - only use arachidonic acid - Physiological function: stomach protection, blood clotting, parturition
COX2: - Induced to express by inflammatory signals (bacterial LPS, IL1, IL2, TNF alpha) - Can use neutral derivatives of AA - Can use severl fatty acids in addition to AA - More active than COX1 at low concentrations of AA |
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Metabolism of arachidonic acid to LTs |
Cell stimulation --> increased cPLA2 and 5-LO
PL --> (cPLA2) --> AA --> (5-LO) --> LTA4 --> LTB4 --> LTC4 --> trasnported out of the cell by leukotrien transporter protein |