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| Endoplasmic reticulum D-myo-inositol 1,4,5-trisphosphate-sensitive stores regulate nuclear factor-kappa B binding activity in a calcium-dependent manner |
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| Author(s): Glazner GW, Camandola S, Geiger JD, Mattson MP |
| Source: JOURNAL OF BIOLOGICAL CHEMISTRY Volume: 276 Issue: 25 Pages: 22461-22467 Published: JUN 22 2001 |
| Times Cited: 16 References: 82 |
| Abstract: The transcription factor nuclear factor-kappaB (NF-kappaB) plays critical roles in neuronal survival and plasticity and in activation of immune responses. The activation of NF-kappaB has been closely associated with changes in intracellular calcium levels, but the relationship be tween the two remains unclear. Here we report that inhibition of endoplasmic reticulum (ER) D-myo-inositol 1,4,5-trisphosphate (IP3)-gated calcium release caused decreased basal NF-kappaB DNA-binding activity in cultured rat cortical neurons. Activation of NF-kappaB in response to tumor necrosis factor-alpha and glutamate was completely abolished when IP3 receptors were blocked, and NF-kappaB activation in response to depletion of ER calcium by thapsigargin treatment was also decreased by IP3 receptor blockade, We further investigated the relationship between IP3 receptor activation and NF-kappaB activity using a cell-free system. Microsomes enriched in the ER were isolated from adult rat cerebral cortex, resuspended, and treated with agents that induce or inhibit ER calcium release, They were then recentrifuged, and the supernatant was added to cytoplasmic extract isolated from the same source tissue. We found that microsomes released an NF-kappaB stimulating signal in response to activation of IP3 receptors or inhibition of the ER Ca2+-ATPase, but not in response to ryanodine. Studies of intact cells and cell-free preparations indicated that the signal released from the ER was not calcium and was heat- and trypsin sensitive. Our data suggest that activation of IP3 receptors is required for a major component of both constitutive and inducible NF-kappaB binding activity in neurons and that decreasing ER intraluminal calcium levels triggers release of a diffusible NF-kappaB-activating signal from the ER. |
| Document Type: Article |
| Language: English |
| Reprint Address: Mattson, MP (reprint author), NIA, Neurosci Lab, Gerontol Res Ctr, NIH, GRC 4F02,5600 Nathan Shock Dr, Baltimore, MD 21224 USA |
Addresses:
1. NIA, Neurosci Lab, Gerontol Res Ctr, NIH, Baltimore, MD 21224 USA
2. Univ Manitoba, Fac Med, Dept Pharmacol & Therapeut, Winnipeg, MB R3E 0T6 Canada
3. Johns Hopkins Univ, Sch Med, Dept Neurosci, Baltimore, MD 21205 USA |
| Publisher: AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC, 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA |
| Subject Category: Biochemistry & Molecular Biology |
| IDS Number: 444RE |
| ISSN: 0021-9258 |
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| | | | | | | | | Record from Web of Science® | | | | | | | | | |