Witam, ja mam sprawę odnośnie nadmiernego pobudzenia receptorów NMDA, bo otóż stwierdzono że nadmierna stymulacja receptorów NMDA powoduje apoptoze komórek stawowych '' Excessive NMDAR stimulation in cartilage may be detrimental increasing activation of pro-apop- totic pathways or decreasing cellular oxidative defence mechanisms.''
''neuronal cells much of our current knowledge of the physiological and pathological functions of NMDAR is based on the study of neuronal cells. Physiological acti- vation of NMDAR promotes cell survival On the other hand pathological activation of NMDAR is detrimental to cell survival20. Pathological activation of NMDAR, with strong calcium fl ux, leads to mitochondrial dysfunction, calpain and MAP kinase activation.20 In circumstances where NMDAR blockade does not result in neuronal death, it can render neurons more vulnerable to mechani- cal trauma. In contrast to pathological activation, physi- ological stimulation of NMDAR results in pro-survival signalling involving the PI3K/Akt pathway, activation of CREB, down-regulation of pro-apoptotic gene expres- sion and boosting of intrinsic anti-oxidant defences.20''
zrodło: Expression and Function of Articular Chondrocyte NMDA Receptors
nie nadmierna stymulacja NMDAR powoduje zwiekszona żywotność komórek ''Inhibition of the PKA and PI3K pathways abolished the protection evoked by NMDA, and inhibition of the MEK pathway significantly diminished this protection. '' żródło:
http://www.ncbi.nlm.nih.gov/pubmed/21185872, i ''Also, neuroprotective levels of
NMDAR activity may stimulate PI3K/Akt
pathway to suppress neuronal apoptosis. The
importance of PI3K/Akt signaling in the
pro-survival activity of NMDARs was
demonstrated in cultured rat cerebellear
granule neurons [62, 67-69]. In this model,
PI3K inhibition with either LY294002 or
wortmanin reduced NMDA protection
against apoptosis induced by trophic
deprivation in low K+
media [62, 67-69].
Also, NMDA activated PI3K [67] and
activated Akt in a PI3K-dependent manner
[62, 68].'' i(z tego samego zrodla) ''to realize that NMDAR effects on GSK3β
depend on the stimulation intensity. For
instance, while low intensity stimulation
reduced the apoptotic activation of GSK3β
[48], excitotoxic stimulation activated this
kinase [89]. Therefore, NMDAR appear to
have bidirectional effects on GSK3β.
Inhibition of GSK3β is another
signaling event that contributes to NMDARprotection against apoptosis.''
żródło -
https://louisville.edu/kscirc/faculty-laboratory-websites/laboratory-of-neurosignalling/pdf/HetmanKharebavaCTMC.pdf
Zmieniony przez - mokremajtk w dniu 2013-09-23 22:52:37