Evaluation of acute antiapoptotic effects of Li+ in neuronal cell cultures.
Li(+) exerts protective effect against several neurotoxins in neuronal cell preparations. Here we examined the antiapoptotic effects of GSK3beta in cerebellar granule neurons (CGNs) in the presence of several neurotoxins. Acute treatment with Li(+) protected neurons against nocodazole and serum/potassium (S/K) deprivation, but were ineffective against kainic acid and MPP(+). Li(+) 5 mM also decreased caspase-3 activation induced by nocodazole and S/K deprivation as measured by Ac-DEVD-p-nitroaniline and the breakdown of alpha-spectrin. All the neurotoxins used in the present study activated GSK3beta, evaluated with a specific antibody phospho-GSK-3beta (Ser9) by Western-blot and immunocytochemistry and were always inhibited by Li(+) 5 mM. Our results implicate Li(+) in the regulation of apoptosis mediated by caspase activation (Type I). Furthermore inhibition of GSK3beta by acute treatment with Li(+) 5 mM is not an indicator of neuroprotection. The acute antiapoptotic function of Li(+) is discussed in terms of its inhibition of Type I pathway, the intrinsic (mitochondrial) apoptotic pathway in cerebellar granule cells.
Yeste
M
M
Unitat de Farmacologia i Farmacognòsia, Facultat de Farmàcia, Universitat de Barcelona, Nucli Universitari de Pedralbes, Barcelona, Spain.
Alvira
D
D
Verdaguer
E
E
Tajes
M
M
Folch
J
J
Rimbau
V
V
Pallàs
M
M
Camins
A
A
D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine / Q000494:pharmacology; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D020169:Caspases / Q000187:drug effects / Q000378:metabolism; D002478:Cells, Cultured; D015259:Dopamine Agents / Q000633:toxicity; D004789:Enzyme Activation / Q000187:drug effects; D018690:Excitatory Amino Acid Agonists / Q000633:toxicity; D005434:Flow Cytometry; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism; D000071679:Glycogen Synthase Kinase 3 beta; D007150:Immunohistochemistry; D007608:Kainic Acid / Q000633:toxicity; D018021:Lithium Chloride / Q000494:pharmacology*; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D018696:Neuroprotective Agents / Q000494:pharmacology*; D015739:Nocodazole / Q000633:toxicity; D051381:Rats; D017207:Rats, Sprague-Dawley
D015259:Dopamine Agents; D018690:Excitatory Amino Acid Agonists; D018696:Neuroprotective Agents; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D000071679:Glycogen Synthase Kinase 3 beta; C000605508:Gsk3b protein, rat; D038362:Glycogen Synthase Kinase 3; D020169:Caspases; D018021:Lithium Chloride; D015739:Nocodazole; D007608:Kainic Acid