3H-1,2-dithiole-3-thione protects PC12 cells against amyloid beta 1–42 (Aβ1–42) induced apoptosis via activation of the ERK1/2 pathway

Chunyan Zhang, Linsen Xie, Fangxia Guan, Yuanbo Cui

Research output: Contribution to journalArticle

Abstract

Aims: Increasing evidence displays that deposition of aggregated β-amyloid (Aβ) leads to neuronal cell apoptosis, thus aggravates the pathological progression of Alzheimer's disease (AD). 3H-1,2-dithiole-3-thione (D3T) has been proved to exert neuroprotective effects. However, the effect of D3T on protecting against Aβ-induced apoptosis and the underlying mechanism are unknown. Main methods: MTT, DCFH-DA assay, LDH release assay, Fluo-3 AM assay, Flow cytometry and Western blot were used to examine cell viability, ROS level, LDH release, intracellular Ca2+ concentration, cell apoptosis and related proteins level respectively. Key findings: In the present study, we found that D3T pretreatment significantly increased cell viability and decreased reactive oxygen species (ROS) levels, lactate dehydrogenase (LDH) levels and the intracellular calcium concentration of rat pheochromocytoma (PC12) cells after Aβ1–42 exposure. In addition, D3T pretreatment inhibited Aβ1–42 induced cell apoptosis as well as protein levels of Bax and Caspase-3 in PC12 cells. Further, D3T markedly activated extracellular regulated protein kinase 1/2 (p-ERK1/2) but not PI3K/Akt signaling. Moreover, the protective effect of D3T against Aβ1–42 induced apoptosis was abolished by the ERK1/2 pathway inhibitor PD98059 while PI3K inhibitor LY294002 had no significant effect. Significance: Taken together, these findings suggest that D3T protects PC12 cells against Aβ1–42 induced apoptosis through activation of the ERK1/2 pathway.

LanguageEnglish (US)
Pages74-81
Number of pages8
JournalLife Sciences
Volume213
DOIs
StatePublished - Nov 15 2018

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Thiones
MAP Kinase Signaling System
PC12 Cells
Chemical activation
Apoptosis
L-Lactate Dehydrogenase
Assays
Phosphatidylinositol 3-Kinases
Amyloid
Reactive Oxygen Species
Cell Survival
Cells
bcl-2-Associated X Protein
2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one
Flow cytometry
Pheochromocytoma
Neuroprotective Agents
Caspase 3
Protein Kinases
amyloid beta-protein (1-42)

Keywords

  • Apoptosis
  • D3T
  • ERK1/2
  • PC12 cells

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Pharmacology, Toxicology and Pharmaceutics(all)

Cite this

3H-1,2-dithiole-3-thione protects PC12 cells against amyloid beta 1–42 (Aβ1–42) induced apoptosis via activation of the ERK1/2 pathway. / Zhang, Chunyan; Xie, Linsen; Guan, Fangxia; Cui, Yuanbo.

In: Life Sciences, Vol. 213, 15.11.2018, p. 74-81.

Research output: Contribution to journalArticle

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