PMID- 24051401 OWN - NLM STAT- MEDLINE DCOM- 20140407 LR - 20211203 IS - 1422-0067 (Electronic) IS - 1422-0067 (Linking) VI - 14 IP - 9 DP - 2013 Sep 18 TI - Involvement of calcium-mediated reactive oxygen species in inductive GRP78 expression by geldanamycin in 9L rat brain tumor cells. PG - 19169-85 LID - 10.3390/ijms140919169 [doi] AB - Treatment with geldanamycin (GA) leads to an increase in [Ca2+]c and the production of reactive oxygen species (ROS) in rat brain tumor 9L RBT cells. GA-exerted calcium signaling was blocked by BAPTA/AM and EGTA. The effect of GA on [Ca2+]c was significantly reduced in the presence of thapsigargin (TG) and ruthenium red (RR). GA-induced GRP78 expression is significantly decreased in the presence of BAPTA/AM, EGTA and RR, suggesting that the calcium influx from the extracellular space and intracellular calcium store oscillations are contributed to by the calcium mobilization and GRP78 expression induced by GA. The induced GRP78 expression is sensitive to added U73122 and Ro-31-8425, pinpointing the involvement of phospholipase C (PLC) and protein kinase C (PKC) in GA-induced endoplasmic reticulum (ER) stress. The antioxidants N-acetylcysteine (NAC), BAPTA/AM, EGTA and H7 also have significant inhibitory effects on ROS generation. Finally, neither H7 nor NAC was able to affect the calcium response elicited by GA. Our results suggest that the causal signaling cascade during GA-inducted GRP78 expression occurs via a pathway that connects PLC to cytoplasmic calcium increase, PKC activation and, then, finally, ROS generation. Our data provides new insights into the influence of GA on ER stress response in 9L RBT cells. FAU - Sun, Fang-Chun AU - Sun FC AD - Department of Bioresources, Da-Yeh University, Changhua 515, Taiwan. fcsun@mail.dyu.edu.tw. FAU - Shyu, Hsin-Yi AU - Shyu HY FAU - Lee, Meng-Shiou AU - Lee MS FAU - Lee, Meng-Shiunn AU - Lee MS FAU - Lai, Yiu-Kay AU - Lai YK LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20130918 PL - Switzerland TA - Int J Mol Sci JT - International journal of molecular sciences JID - 101092791 RN - 0 (Antibiotics, Antineoplastic) RN - 0 (Benzoquinones) RN - 0 (Chelating Agents) RN - 0 (Endoplasmic Reticulum Chaperone BiP) RN - 0 (Estrenes) RN - 0 (Heat-Shock Proteins) RN - 0 (Indoles) RN - 0 (Lactams, Macrocyclic) RN - 0 (Maleimides) RN - 0 (Pyrrolidinones) RN - 0 (Reactive Oxygen Species) RN - 112648-68-7 (1-(6-((3-methoxyestra-1,3,5(10)-trien-17-yl)amino)hexyl)-1H-pyrrole-2,5-dione) RN - 131848-97-0 (Ro 31-8425) RN - EC 2.7.11.13 (Protein Kinase C) RN - EC 3.1.4.- (Type C Phospholipases) RN - SY7Q814VUP (Calcium) RN - Z3K3VJ16KU (geldanamycin) SB - IM MH - Animals MH - Antibiotics, Antineoplastic/*toxicity MH - Benzoquinones/*toxicity MH - Brain Neoplasms/metabolism/pathology MH - Calcium/*metabolism MH - Cell Line, Tumor MH - Chelating Agents/pharmacology MH - Endoplasmic Reticulum Chaperone BiP MH - Endoplasmic Reticulum Stress/drug effects MH - Estrenes/pharmacology MH - Gene Expression/*drug effects MH - Heat-Shock Proteins/genetics/*metabolism MH - Indoles/pharmacology MH - Lactams, Macrocyclic/*toxicity MH - Maleimides/pharmacology MH - Protein Kinase C/metabolism MH - Pyrrolidinones/pharmacology MH - Rats MH - Reactive Oxygen Species/*metabolism MH - Type C Phospholipases/antagonists & inhibitors/metabolism PMC - PMC3794827 EDAT- 2013/09/21 06:00 MHDA- 2014/04/08 06:00 PMCR- 2013/09/01 CRDT- 2013/09/21 06:00 PHST- 2013/07/24 00:00 [received] PHST- 2013/08/19 00:00 [revised] PHST- 2013/09/09 00:00 [accepted] PHST- 2013/09/21 06:00 [entrez] PHST- 2013/09/21 06:00 [pubmed] PHST- 2014/04/08 06:00 [medline] PHST- 2013/09/01 00:00 [pmc-release] AID - ijms140919169 [pii] AID - ijms-14-19169 [pii] AID - 10.3390/ijms140919169 [doi] PST - epublish SO - Int J Mol Sci. 2013 Sep 18;14(9):19169-85. doi: 10.3390/ijms140919169.