TY - JOUR
T1 - 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
AU - Zhang, Chunyan
AU - Xie, Linsen
AU - Guan, Fangxia
AU - Cui, Yuanbo
N1 - Publisher Copyright:
© 2018
PY - 2018/11/15
Y1 - 2018/11/15
N2 - 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.
AB - 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.
KW - Apoptosis
KW - Aβ
KW - D3T
KW - ERK1/2
KW - PC12 cells
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U2 - 10.1016/j.lfs.2018.10.025
DO - 10.1016/j.lfs.2018.10.025
M3 - Article
C2 - 30326219
AN - SCOPUS:85054882683
SN - 0024-3205
VL - 213
SP - 74
EP - 81
JO - Life Sciences
JF - Life Sciences
ER -