MCM-SV-Eicosanoids and Lipid Mediators-2 (2)

which cells produce leukotrienes? Why are they called ‘trienes”? Which receptor do they act through and what do they do?

Leukocytes, mast cells, oesinophils and other immunocells; trienes = 3 double bond in succession; act through GPCR and has pro-inflammatory effects (including inflammatory effect in asthma); They also play a role in vasoconstriction, smooth muscle constriction, musocal secretion, and constriction of airways

Explain the biosynthesis pathway for leukotrienes. What are the three cysteinyl leukotrienes? What drug inhibit this synthesis? What chemical is an antagonist to leukotrienes?

AA —> LOX 5 —> LTA4 —> LTBCD4; LTB4, LTC4, LTD4 are the three cysteinyl leukotreins

zyflo (zileutron) inhibit this synthesis (asthma medicine)

singulair (montelukast) acts as an antagonist for leukotriene receptors

What are peptidoleukotrienes? What are SRS-A? What does SRS-A do? Where is it implicated?

leukotrienes that has some peptides attached. SRS-A are the Lts that triggers anaphylatic. SRS-A is released from lungs by immunological stress and causes smooth muscle contraction of bronchi.

Implicated by hypersensitivity reaction.

What are the functions of neutrophils? What does activated neutrophils secrete? What is this chemical’s function? How can neutrophils cause emphysema? What is PGP?

Neutrophils can created inflammation of the lungs. This inflammation can cause diseases such as COPD, cystic fibrosis,…

Activated neutrophils secrete ROS which is proinflammatory while inhibiting anti-inflammatory effects of glucocorticoids

Neutrophils can cause emphysema by degrading elastin/collagin via:

1. secretion of elastase and proteinase-3 which degrades elastin and secrete mucus

2. secretion of MMP 8/9 which causes elastin and collagen degradation

PGP is the biproduct of elastin/collagen degradation by MMP8/9. It acts as a neutrophil attractang

What is the function of LTA4H and why does smoke inhibits its action?

LTA4H helps with the synthesis of LTB4 and also degrades PGP. Smoke causes acetylation of PGP which makes it harder for it to be degraded by LTA4H

Compare and Contrast the functions of LTB4 and LTC/D4

LTB4: Increase vasopermeability, increase IFN-gamma, increase IL1 and IL2, leukocyte aggregation, T-cell proliferation

LTC4/LTD4: Increase vasopermeability, increase IFN-gamma. bronchoconstriction

Which cells produce eicosanoids during inflammation? Discuss the role of eicosanoids during inflamation? How can PGs have contradictory inflammation roles? What eicosaonoids play a role in resolving inflammation

granucyte, macrophages, neutrophils, platelets, mast cells, endothial cells.

Role of eicossanoids in inflammation:

LTB4: chemoattractant

LTs: vasopermeability

cystein LTs: smooth muscle contract

TXA4: platelet aggregation

PGH2: proinflammatory

PGs’ effects is determined by the different EP receptors.

Lipoxins resolve inflammation

What is the relationship between leukotrienes and rheumatoid arthritis?

Leukotriens have found to develop rheumatoid arthritis, specifically LTB4

Describe the synthesis of lipoxins (LX). What are the two discovered Lipoxins? What do they do? How does Aspirin affect this?

AA —> LOX5 and LOX 15 —> LXA4 and LXB4;

They oppose some leukotriens function by:

1. They resolves inflammation

2. prevent platelet degranulation and chemotaxis

3. inhibit vasoconstriction by VD4

4. could be used to reduce constriction of airways

Aspirin creates 15-epi- LXA4 which inhibits inflammation and carcinogenesis.

Draw out the relationship between Cox1, Cox2, and cancer

How does cox-2 derived PGE2 cause cancer?

through five ways

1. increases cell proliferation and angiogenesis

2. decreases apoptosis

3. increase cell invasiveness

4. decreases immune surveilence

5. inhibit function and differentiation of dendritic cells

What is anandamide? Describe how it is produced/degraded. explain one theory on why chocolate is so addictive

anadamide is an endogenous cannaboid binding receptor;

phosphotidylethanolamine is cleaved by TEA (transacyclase) which result in AA binding to ethanolamine. This is then cleaved by phospholipase D which results in AA + ethanolamine.

Anandamid promotes analgesic effects via CB1 (CNS) and CB2 (peripheral)

Chocolate is addictive because it has compounds that slow down anandamid degradation (fatty acid amide hydrolysis)

Describe the synthesis and function of isoprosteins? What lab test used this for? How can this have anti-cancer effects?

isoprosteins are produced via free radicals. PLA2 release these altered AAs which can covalently modify lots of stuff. This test is used to assess oxidative stress .

This can have anti-cancer effects if produced from DHA

What is hemostasis? What are the four phases?

hemostasis is clot formation

1. vascular phase

2. platelet phase

3. coagulation phase

4. fibrinolytic phase

What are the three ways in which endolithium cells have anti-thrombotic properties?

1. they have PGI2 which has anti platelet aggregation and stimulates smooth muscle relaxation

2. They have NO (aka EDRF, endolitheum derived relaxing factor)

3. Heparin sulfate and thrombomodulin

Describe how production of TXA2 is initiated when there is damage to blood vessels. How does TXA2 help with clot formation

damage to vessels —> collagin exposed —> platelet attaches —> PLA2 creates TXA2

TXA2 causes platelet aggregation, vasoconstriction, degranulation of platelets

What is platelet aggregation controlled by? How does aspirin and omega 3 help reduce platelet aggregation

controlled by levels of PGI2 and TXA2; aspirin inhibits COX 1 which means no production of TXA2;

OMEGA 3 slows down synthesis of TXA2 and reduce production of proinflammatory eicosanoids