OBJECTIVES: Acute treatment with valproate (VPA) or lithium (Li+) protects cerebellar granule cells (CGC) against apoptosis induced by low potassium (K+) (5 mM). As the protection induced by VPA is absolutely dependent on insulin, in contrast to the observed effects of Li+, we decided to study the different role of the PI3K/PKB pathway in the neuroprotective effects of both drugs. METHODS: We have studied the neuroprotection elicited by Li+ or VPA in cultures of rat CGC. We induced the apoptosis by switching to a medium with a low concentration of K+ or by adding C2-ceramide to the cultures. We studied the effect of Li+ and VPA on viability and on the regulation of the PI3K/PKB pathway. RESULTS AND CONCLUSIONS: Insulin also protects against low K(+)-induced apoptosis in CGC, probably through its interaction with an insulin-like growth factor receptor. Moreover, whereas Li+ protects against the apoptosis induced by C2-ceramide, VPA cannot, probably due to the inhibition of protein kinase B (PKB) caused in this apoptotic stimulus. These results suggest that VPA protects against low K(+)-induced apoptosis by acting on the PI3K/PKB pathway; however, VPA does not affect the increase of PKB activity caused by insulin in these cells. The protection by Li+ is independent of this transduction pathway. Moreover, Li+ blocks the caspase 3 activation induced by low K+, whereas neither VPA nor insulin affects this activation.
OBJECTIVES: Acute treatment with valproate (VPA) or lithium (Li+) protects cerebellar granule cells (CGC) against apoptosis induced by low potassium (K+) (5 mM). As the protection induced by VPA is absolutely dependent on insulin, in contrast to the observed effects of Li+, we decided to study the different role of the PI3K/PKB pathway in the neuroprotective effects of both drugs. METHODS: We have studied the neuroprotection elicited by Li+ or VPA in cultures of rat CGC. We induced the apoptosis by switching to a medium with a low concentration of K+ or by adding C2-ceramide to the cultures. We studied the effect of Li+ and VPA on viability and on the regulation of the PI3K/PKB pathway. RESULTS AND CONCLUSIONS: Insulin also protects against low K(+)-induced apoptosis in CGC, probably through its interaction with an insulin-like growth factor receptor. Moreover, whereas Li+ protects against the apoptosis induced by C2-ceramide, VPA cannot, probably due to the inhibition of protein kinase B (PKB) caused in this apoptotic stimulus. These results suggest that VPA protects against low K(+)-induced apoptosis by acting on the PI3K/PKB pathway; however, VPA does not affect the increase of PKB activity caused by insulin in these cells. The protection by Li+ is independent of this transduction pathway. Moreover, Li+ blocks the caspase 3 activation induced by low K+, whereas neither VPA nor insulin affects this activation.
Authors: Xuehua Xu; Annette Müller-Taubenberger; Kathryn E Adley; Nadine Pawolleck; Vivian W Y Lee; Claudia Wiedemann; Talvinder S Sihra; Markus Maniak; Tian Jin; Robin S B Williams Journal: Eukaryot Cell Date: 2007-04-13
Authors: M Yeste; D Alvira; E Verdaguer; M Tajes; J Folch; V Rimbau; M Pallàs; A Camins Journal: J Neural Transm (Vienna) Date: 2006-08-17 Impact factor: 3.575
Authors: Leandre Carmen Wilot; Andressa Bernardi; Rudimar Luiz Frozza; Ana Lucilia Marques; Helena Cimarosti; Christianne Salbego; Elizabete Rocha; Ana Maria Oliveira Battastini Journal: Neurochem Res Date: 2007-05-04 Impact factor: 3.996