Abstract

The endoplasmic reticulum (ER) is a principal site for protein synthesis, protein folding, calcium storage, and calcium signaling. Thapsigargin (TG), an inducer of ER stress, inhibits ER-associated Ca²⁺-ATPase and disrupts Ca²⁺ homeostasis. ER stress plays an important pathogenetic role in Alzheimer's disease, Parkinson's disease, Huntington's disease, Lou Gehrig's disease, and prion protein diseases. This study was conducted to evaluate the protective mechanisms of Scrophularia ningpoensis (SN) extracts and chemicals on TG-stimulated U-87MG cells. In this study, the recovery activities of E-harpagoside (EHA), harpagide (HA), 8-O-E-p-methoxycinnamoylharpagide (MH), aucubin (AB), cinnamic acid (CA), p-coumaric acid (pCA), p-methoxycinnamic acid methyl ester (MME), caffeic acid (CFA), ferulic acid (FA), and (E)-p-methoxycinnamic acid (MA) on TG-stimulated U-87MG cells were evaluated. The results revealed that SN, MME, CFA, and MH showed considerable recovery effects. Therefore, SN, MME, CFA, and MH were selected to evaluate the gene expression profile of U-87MG cells by using microarray analysis and real-time RT-PCR. The results of this analysis revealed that cell cycle, proliferation, protein folding, and anti-apoptosis-related genes were up-regulated in SN, MME, CFA, and MH-treated U-87MG cells. In addition, significant decreases in apoptosis, the MAPK signaling pathway, and mitochondria-related gene expressions were observed in SN-, MME-, CFA-, and MH-treated U-87MG cells. Thus, SN, MME, CFA, and MH might affect neurodegenerative diseases. © 2009 Elsevier Inc. All rights reserved.

Author keywords

Gene expression profile; Scrophularia ningpoensis; Thapsigargin; U-87MG cells

Indexed keywords

EMTREE drug terms: aucubin; caffeic acid; cinnamic acid; ferulic acid; harpagide; harpagoside; mitogen activated protein kinase; para coumaric acid; plant extract; Scrophulariaceae ningpoensis extract; thapsigargin; unclassified drug

EMTREE medical terms: apoptosis; article; astrocytoma cell; biological activity; cell cycle; cell proliferation; cell stimulation; controlled study; cytotoxicity; drug mechanism; gene expression; gene expression profiling; genome analysis; human; human cell; microarray analysis; mitochondrion; neuroprotection; nucleotide sequence; priority journal; protein folding; real time polymerase chain reaction; reverse transcription polymerase chain reaction; Scrophulariaceae; Scrophulariaceae ningpoensis; signal transduction; unindexed sequence; upregulation

MeSH: Apoptosis; Astrocytoma; Cell Cycle; Cell Line, Tumor; Cell Proliferation; Cell Survival; DNA, Mitochondrial; Gene Expression; Gene Expression Profiling; Gene Expression Regulation; Humans; Plant Extracts; Protein Folding; Scrophularia; Thapsigargin
Medline is the source for the MeSH terms of this document.

Species Index: Scrophularia ningpoensis

Molecular Sequence Numbers: GENBANK,NM_000266(referenced), NM_000546(referenced), NM_000963(referenced), NM_001255(referenced), NM_001330(referenced), NM_001798(referenced), NM_001889(referenced), NM_002020(referenced), NM_002089(referenced), NM_002105(referenced), NM_002157(referenced), NM_002250(referenced), NM_002575(referenced), NM_002757(referenced), NM_002852(referenced), NM_002975(referenced), NM_003318(referenced), NM_004394(referenced), NM_004494(referenced), NM_005030(referenced), NM_005483(referenced), NM_006351(referenced), NM_006426(referenced), NM_006494(referenced), NM_006845(referenced), NM_012090(referenced), NM_012094(referenced), NM_012238(referenced), NM_014264(referenced), NM_014496(referenced), NM_016195(referenced), NM_016343(referenced), NM_017927(referenced), NM_018135(referenced), NM_020242(referenced), NM_021007(referenced), NM_022086(referenced), NM_023035(referenced), NM_024060(referenced), NM_032351(referenced), NM_033297(referenced), NM_033642(referenced), NM_138444(referenced), NM_145113(referenced), NM_145859(referenced), NM_181078(referenced), NM_181803(referenced), NM_182776(referenced), NM_182826(referenced), NM_199176(referenced)

Chemicals and CAS Registry Numbers: aucubin, 479-98-1; caffeic acid, 27323-69-9, 331-39-5; cinnamic acid, 4151-45-5, 538-42-1, 621-82-9; ferulic acid, 1135-24-6, 24276-84-4; harpagide, 6926-08-5; harpagoside, 19210-12-9; mitogen activated protein kinase, 142243-02-5; para coumaric acid, 7400-08-0; thapsigargin, 67526-95-8;DNA, Mitochondrial; Plant Extracts; Thapsigargin, 67526-95-8