PMID- 19720044 OWN - NLM STAT- MEDLINE DCOM- 20091030 LR - 20131121 IS - 1096-0384 (Electronic) IS - 0003-9861 (Linking) VI - 490 IP - 2 DP - 2009 Oct 15 TI - Apoptotic inducers activate the release of D-aspartate through a hypotonic stimulus-triggered mechanism in PC12 cells. PG - 118-28 LID - 10.1016/j.abb.2009.08.017 [doi] AB - We have characterized release of D-aspartate (D-Asp), a regulator of hormone synthesis and secretion, via a volume-sensitive organic anion channel (VSOC) in PC12 cells by studying its response to apoptotic stimuli. PC12 cells have been demonstrated to endogenously synthesize D-Asp. Apoptotic inducers, including staurosporin (STS), tumor necrosis factor (TNF)-alpha, H(2)O(2), and C2-ceramide, activate the release of D-Asp through a hypotonic stimulus-triggered mechanism. Putative blockers of the anion channel, 5-nitro-2-(3-phenylpropylamino)benzoic acid (NPPB) and 4,4'-diisothiocyanostilbene-2,2'-sulphonic acid (DIDS), significantly inhibited stress-induced D-Asp release under hypotonic conditions following the application of apoptotic inducers. Hypotonic conditions are essential for activation by apoptotic inducers. Phorbol 12-mirystate 13-acetate and the Ca(2+) ionophore A23187 increased D-Asp efflux via the VSOC, implying the involvement of intracellular Ca(2+) in the activation of the D-Asp efflux. However, hypotonic stress and STS had no effect on the concentration of intracellular Ca(2+) in PC12 cells. Furthermore, an unknown EGTA-sensitive factor(s), other than Ca(2+), and peroxynitrite may play pivotal roles in STS-enhanced D-Asp release. FAU - Furuchi, Takemitsu AU - Furuchi T AD - Laboratory of Biomolecular Science, Department of Pharmaceutical Life Sciences, Kitasato University, 5-9-1 Shirokane, Minato-ku, Tokyo 108-8641, Japan. FAU - Suzuki, Toshiyuki AU - Suzuki T FAU - Sekine, Masae AU - Sekine M FAU - Katane, Masumi AU - Katane M FAU - Homma, Hiroshi AU - Homma H LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20090829 PL - United States TA - Arch Biochem Biophys JT - Archives of biochemistry and biophysics JID - 0372430 RN - 0 (Hypotonic Solutions) RN - 0 (Ion Channels) RN - 0 (Ionophores) RN - 0 (N-acetylsphingosine) RN - 0 (Nitrobenzoates) RN - 0 (Tumor Necrosis Factor-alpha) RN - 268B43MJ25 (Uric Acid) RN - 30KYC7MIAI (Aspartic Acid) RN - 37H9VM9WZL (Calcimycin) RN - 3A35O9G3YZ (5-nitro-2-(3-phenylpropylamino)benzoic acid) RN - BBX060AN9V (Hydrogen Peroxide) RN - H88EPA0A3N (Staurosporine) RN - NGZ37HRE42 (Sphingosine) RN - NI40JAQ945 (Tetradecanoylphorbol Acetate) SB - IM MH - Animals MH - Apoptosis/*drug effects/*physiology MH - Aspartic Acid/chemistry/*metabolism MH - Calcimycin/pharmacology MH - Hydrogen Peroxide/pharmacology MH - Hypotonic Solutions MH - Ion Channels/drug effects/metabolism MH - Ionophores/pharmacology MH - Nitrobenzoates/pharmacology MH - PC12 Cells MH - Rats MH - Sphingosine/analogs & derivatives/pharmacology MH - Staurosporine/pharmacology MH - Stereoisomerism MH - Tetradecanoylphorbol Acetate/pharmacology MH - Tumor Necrosis Factor-alpha/pharmacology MH - Uric Acid/pharmacology EDAT- 2009/09/02 06:00 MHDA- 2009/10/31 06:00 CRDT- 2009/09/02 09:00 PHST- 2009/06/24 00:00 [received] PHST- 2009/08/25 00:00 [revised] PHST- 2009/08/27 00:00 [accepted] PHST- 2009/09/02 09:00 [entrez] PHST- 2009/09/02 06:00 [pubmed] PHST- 2009/10/31 06:00 [medline] AID - S0003-9861(09)00278-1 [pii] AID - 10.1016/j.abb.2009.08.017 [doi] PST - ppublish SO - Arch Biochem Biophys. 2009 Oct 15;490(2):118-28. doi: 10.1016/j.abb.2009.08.017. Epub 2009 Aug 29.