Cell Growth Flashcards
What does EGF do?
Epidermal grwoth factor
Produced by stromal fibroblasts
Stimulates corneal epithlial migration and epithelial and fibroblast proliferation
By increasing fibronectin production
What are functions of TGF-beta
TGF-b1 casues dose related inhibtion of epithelial cell proliferation and inhibits stimulatory effect of EGF
TGF-b2 localised to superficial limbal epithelial cells - transdifferentiation of conj and corneal epithelium
TGF b3 stimulates proliferation of stromal fibroblasts and increased collagen and fibronectin synthesis
What does PDGF platelet derived growth factor do
Stimulate limbal stem cell proliferation
What does fibroblast growth factor do
Stimulates epithelial and fibroblast proliferation and production of ECM by fibroblastsW
What proteins make up ECM
Collagen
Laminin
Fibronectin
Plysaccharide glycosaminoglycans (negative charge, repeating disaccharide chain)
What is fibronectin structure? Role?
2 polypeptide chains linked by disulphide bond S-S
6 domains on each with binding sites for integrins, proteoglycans and collagen
Found at level of stromal side of Descemet’s
ROLE: Promote adhesion between cells and extracellular matrix via integrin a5b1 in wounded cornea
Forms temporary scaffold in injury for epithelial migration and adjesion
What stimualtes fibronectin production
Epidermal growth factor
Tissue growth factor B
What are laminin structures? Where found?
Role?
Large multidoamin glycoprotein
3 polypeptide chains
Found in lamina lucida of basal almina
Strctural component of basement membrane
Growth, migration, differentaition
What is an important laminin in corneal wound healing
laminin-5
Becomes continuous after wound closure
What are integrin structure? Function?
TRansmembrane glycoprotein
alpha and beta subunits
Mediate attachment of cells to ECM and cell-cell adhesion.
Transduce biochemical signals from ECM to the interior of the cell via phosphorylation cascades
Receptors for laminin, collagen, fibronectin, vitronectin, ICAM1, ICAM2
What integrin is important in hemodesmosomes
a6b4 integrin
What are mechanisms of cell surface signalling
GPCR
Adnylate cyclase - cAMP
Phophoinoitidase C (PIC) - 1,2 DAG, inositol, calcium
Ligand gated ion channels - nAChR
Tyrosine kinase linked receptro - EGF, PDGR
Structure/function of GPCRs
Guanin nucleotide - coupling protein
Effector protein - may be enzyme or ion channelW
What receptors activate adenylate cyclase?
B1 and B2 adrenergic receptors
TSH
ACTH
Glucagon
H2
What receptors inhibit adenylate cyclase?
a2 adrenergic
M muscarinic Ach
What receptros activate phosphoinositidase C (PIC) to result in 1,2 - DAG, inostol, claclium?
a1 adrenergic
H1
Endothelin
Platelet activating fators
What receptor activates nucleotide phosphodiesterase
RhodopsinW
What is a nicotinic ACh receptor? Muscarninic?
Nicotinic - ligand gated ion channel
Muscarinic - inhibits adenylate cyclase
What are beta adrenergic receptors
Activate adenylate cyclase
What are alpha 1 and alpha 2 adrenergic receptors
alpha 1 - activates PIC
Alpha 2 - inhibits adenylate cyclase
What are cadherins
Simpla transmembrane glycoproteins - calcium dependent cell adhesion
Zonula adherens and desmosome connections between epithelial cells
Homophillic binding of cadherins on adjacent cells
What are the phases of apoptosis
- precondensation - gene within cell reposnibel for apoptosis is induced
- Condensation - cytoplasmic and nuclear volume DECREASE
Chromatic condenses and interactions between cell and adjacent cells lost
Development of plasma membrane blebs - Fragmentation - non-lysosomal Ca and Mg dependent endonucleases break down DNA into smaller apoptotic bodies
Nucleus become pyknotic - Final phase - phagocytosis of apoptotic bodies and degradation by lesosommal enzymes, no immune reaction
Which factors activate apoptosis
Growth factor withdrawal
Glutamage and dopamine
TNF
TGF-beta
Calcium
Glucocorticoids
Iatrogenic factors - radiation, chemotherapy, toxins - ethanol, beta amyloid
What gene promots apoptosis?
BAX
What gene inhibits apoptosis
Bcl 2
