Targeting eNOS for stroke protection Li-ping Wu 2004-10-13
Targeting eNOS for stroke protection Li-ping Wu 2004-10-13
Background L-arginine nitric oxide synthase (NOS) eNOS NO In vascular diseases >Neuroprotective:increasing cerebral Blood flow during brain ischemia >Vasodilatory >Anti-inflammatory >Antithrombotic >Antiproliferative
Background nitric oxide synthase (NOS) L-arginine NO ➢Neuroprotective:increasing cerebral Blood flow during brain ischemia ➢Vasodilatory ➢Anti-inflammatory ➢Antithrombotic ➢Antiproliferative eNOS In vascular diseases
Main isomers of NOS Constitutively expressed CNOS > Calcium-dependent consitutive form Including: 00 Neuronal(nNOS) Endothelial (eNOS) > iNOS Induced in inflammatory and other cell types by stimuli such as endotoxin and proinflammatory inducible form cytokines Calcium-independent
Main isomers of NOS cNOS consitutive form iNOS inducible form ➢ Constitutively expressed ➢ Calcium-dependent ➢ Including: ➢ Induced in inflammatory and other cell types by stimuli such as endotoxin and proinflammatory cytokines ➢ Calcium-independent Neuronal (nNOS) Endothelial (eNOS)
TeNOS:neuroprotective (knocked out) regional cerebral blood flow cerebral infarction nNOS
eNOS: neuroprotective eNOS nNOS cerebral infarction regional cerebral blood flow (knocked out)
TeNOS:neuroprotective L-NAME (inhibiting activity) eNOS regional cerebral blood flow cerebral infarction (lacking)
eNOS: neuroprotective L-NAME eNOS nNOS cerebral infarction regional cerebral blood flow (lacking) (inhibiting activity)
TeNOS:neuroprotective enhancing NO production) eNOS regional cerebral blood flow L-arginine cerebral infarction nNOS
eNOS nNOS L-arginine cerebral infarction regional cerebral blood flow (enhancing NO production) eNOS: neuroprotective
TeNOS:neuroprotective Enhanacing eNOS function Increuse the number of cireuluting Endothelial Progenitor cells (EPCS) Contribute to neovasularization after ischemia stroke
eNOS: neuroprotective Enhanacing eNOS function Increase the number of circulating Endothelial Progenitor cells (EPCs) Contribute to neovasularization after ischemia stroke
Janus effect of NO in the brain brain ischemia nNOS eNOS iNOS NO toxic to surrounding neurons neuroprotective secondary damage
Janus effect of NO in the brain brain ischemia nNOS NO toxic to surrounding neurons iNOS secondary damage eNOS neuroprotective
What we should do eNOS 2 upregulate and/or activate ow nNOS inhibit iNOS
What we should do eNOS nNOS iNOS upregulate and/or activate inhibit how
How to upregulate/activate eNOS Statins Steroid hormones Physical activity Nutrients
How to upregulate/activate eNOS Statins Steroid hormones Physical activity Nutrients