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8 Cards in this Set

  • Front
  • Back

Structure of cytokine receptors (multisubunit)

Usually heterodimer


alpha: binding cytokine


beta (larger intracellular domain): produce intracellular signals

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

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

Difference between the biochemical composition of cytokines and prostaglandins

Cytokine: Low molecular weight protein


Porstaglandin: Synthesized from fatty acid

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

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

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

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