Sunghyangjungisan protects PC12 cells against neurotoxicity elicited by withdrawal of trophic support via CRE activation.
Sunghyangjungisan (SHJS) is a commonly prescribed drug for cerebrovascular diseases in Oriental medicine. The water extract of SHJS was found to be protective against neurotoxicity elicited by deprivation of tropic factors. SHJS inhibited the activation of caspase 3-like protease and nucleosome-sized DNA fragmentation in serum-deprived PC12 Pheochromocytoma cells. Interestingly, pretreatment with an inhibitor of protein kinase A, KT5720 inhibited the neuroprotective effects of SHJS via inhibition of capase 3-like protease activation. When PC12 cells were treated with SHJS, Ser133 phosphorylation of cAMP-responsive elements binding protein (CREB), a transcription factor, was also increased in a time- and dose-dependent manner. In addition, CRE DNA binding activity of CREB was also increased in a time-dependent manner. SHJS-induced CRE binding activity was blocked by KT5720. Taken together, we suggest the possibility that SHJS may provide a neuroprotective effects on serum-deprived apoptosis of PC12 cells in a CREB- and CRE-dependent manner.
Kim
Myung-Sunny
MS
Institute of Medical Science, Wonkwang University, Iksan Chonbuk, South Korea.
Lee
Kang-Min
KM
Jung
Hun
H
Moon
Byung-Soon
BS
Ko
Chang-Bo
CB
Lee
In
I
Park
Raekil
R
D000818:Animals; D002227:Carbazoles; D053148:Caspase 3; D061945:Caspase Inhibitors; D016895:Culture Media, Serum-Free; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism*; D019610:Cytoprotection / Q000187:drug effects*; D053938:DNA Fragmentation / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D007211:Indoles / Q000494:pharmacology; D008518:Medicine, East Asian Traditional; D018696:Neuroprotective Agents / Q000494:pharmacology*; D016716:PC12 Cells; D010766:Phosphorylation; D010936:Plant Extracts / Q000494:pharmacology*; D010946:Plants, Medicinal; D011758:Pyrroles / Q000494:pharmacology; D051381:Rats; D015842:Serine Proteinase Inhibitors / Q000494:pharmacology; D013997:Time Factors
D002227:Carbazoles; D061945:Caspase Inhibitors; D016895:Culture Media, Serum-Free; D017362:Cyclic AMP Response Element-Binding Protein; D007211:Indoles; D018696:Neuroprotective Agents; D010936:Plant Extracts; D011758:Pyrroles; D015842:Serine Proteinase Inhibitors; C057416:KT 5720; C505410:Casp3 protein, rat; D053148:Caspase 3