Growth Factors II.docx

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Biological Sciences
Michelle Aarts

Platelet-Derived Growth Factor acts locally on injured blood vessels Whole blood serum is required for growth of certain cells in lab Serum prepared fromcell-free plasma has little or no mitogenic activity-> this activity can be restored by adding material released from blood platelets to sera therefore, the mitogenic principle in whole blood serum may be derived from platelets PDGF: Platelet-Derived Growth Factor - Is released from platelets during platelet aggregation in the process of blood clot formation - At sites of wounds, the platelets adhere to the endothelial lining of the blood vessel in such a way as to plug the defect”platelet adhesion” - Also release chemical messengers that stimulate contraction of the injured vessels to prevent further loss of blood “platelet granular release” - At site of injury, platelets release PDGF in response to thrombin - Role of PDGF at such site: 1) Induce proliferation of smooth muscle cells with in the arterial wall- the intima- as part of wound healing process.i.e fail to form in animals whose platelet function is inhibited by drugs - PDGF localized within α granules - Interaction of platelets with localized surfaces of damaged blood vessels provide for a site-specific release mechanism of PDGF to act as a local hormone - Due to wide distribution of smooth muscle cells throughout the body, this necessitates such specialized mode of hormone delivery - Atherosclerosis results from endothelial disruption due to many causes: proliferation of smooth muscle cells, formation of large amounts of collagen matrix by the proliferated smooth muscle cells, deposition of lipid etc. these plaques impede blood flow to brain resulting in brain stroke etc. PDGF plays a domiant role in development of atherosclerosis and it’s a also a potent vasoconstrictor. Structure of PDGF - PDGF consists of family of molecules wherein each peptide is a heterodimer composed of A and B chnain. The two chains share 60% sequence id & can dimerize to from PDGF-AA or PDGF-BB & PDGF-AB. - The dominant form PDGF-AB. - 2 PDGF receptor subtypes: one that recognizes all 3 PDGF varieties and a 2 receptor that binds only the BB variety - The existence of 2 receptors is bio important and they have diff functions—regulatory flexibility in response to PDGF. Epidermal Growth factor stimulates proliferation and keratinisation of epidermal tissue EGF: epidermal growth factor - Enhances cell proliferation in the deepest layer (basal layer) of the skin Mouse EGF: 50 aa , conformationally restricted by 3 intrachain disulfide bonds. Is found within salivary gland cobined with arginine esterase. Arginine esterase is a EGF-binding protein. EGF and NGF lots of similarities: i.e NGF found in submaxillary glands, also binds to a similar but not identical arginine esterase EGF and NGF derived from inactive precursors, similar biosynthesis & activation, under similar genetic locus control? Also, synthesis of both peptides is androgen-dependent Biological effects of EGF in mammals: 1)enhanced proliferation and differentiation (keratinisation) of the epidermis 2) increased growth and maturation of fetal pulmonary epithelium 3) stimulation of orithinine decarboxylase activity and DNA synthesis in the mucosa of the digestive tract -b/c EGF is not entirely destroyed in digestive tract, it may act directly on tissues of this dig. Tract 4) acceleration of healing of wounds of the corneal epithelium, phophorylation of membrane and nuclear properties - major growth promoting agent in breast milk Salivary EGF may play a role in wound-healing of the skin and gastric mucosa.i.e licking enhances wound- healing and application of EGF to a wound accelerated healing process.  EGF-rich excreta i.e saliva, tears etc have an imp role in promotion of wound healing Urogastrone: potent inhibitor of gastric acid secretion Found in urine Single polyp chain with 3 disulfide bonds—similar to mouse EGF length. Is a gastrointestinal peptide, inhibitory to gastric acid secretion at gastric mucosa Both egf and urogastrone stimulate DNA synthesis within human fibroblasts Both EGF and urogastrone elevated during pregnancy ~ evidence suggests that urogastrone human hormone equivalent of mouse EGF. Receptor [Rapid activation of cAMP-dependent phophorylation system] EGF binds to membrane receptors Intrinsic tyrosine kinase activity is triggered Rise in Ca concns Receptor internalization Receptor degradation Specific gene transcription in mins D
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