Acrylamide (ACR) is a potent toxin that affects the human nervous system. However, the underlying mechanism of ACR neurotoxicity remains poorly understood. In the present study, we investigated whether ACR induces mitochondrion-dependent apoptosis and the involved signaling pathways in PC12 cells. ACR exposure activated the mitochondrial apoptotic pathway in PC12 cells and triggered the up-regulation of Bax/Bcl-2 ratio, excessive release of cytochrome c, cleavage of capase-9 and caspase-3, depolarization of the mitochondrial membrane, structural damages to the mitochondria, and compaction of nuclear heterochromatin. ACR-induced oxidative stress was also observed based on distinct increase in cellular reactive oxygen species (ROS) and malondialdehyde (MDA), and significant decrease in glutathione (GSH). Mitogen-activated protein kinases (MAPK) signaling including extracellular signal-regulated protein kinases (ERK), c-Jun N-terminal kinases (JNK), and p38 were phosphorylated by ROS overproduction in PC12 cells in a time-and dose-dependent manner. ACR promoted the translocation of nuclear factor E2-related factor 2 (Nrf2) from the cytosol to the nucleus, thereby enhancing the expression of downstream γ-glutamyl-cysteine synthetase (γ-GCS). The regulation of Nrf2 activation by MAPK pathways was confirmed by the blockade of MAPK pathways. The suppression of JNK and p38 pathways showed a protective effect on ACR-induced mitochondrial dysfunction and apoptosis. Nrf2 knockdown further enhanced MDA production and reduced GSH generation induced by ACR. These results suggest that MAPK and Nrf2 signaling pathways contribute to mitochondrion-mediated apoptosis induced by ACR in PC12 cells.
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- AT101
- 凋亡试剂盒
Annexin V-FITC/PI Apoptosis Kit(细胞凋亡试剂盒-适用贴壁细胞 除C6流式细胞仪以外的流式细胞仪)
- ¥860.00 – ¥1,510.00
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- AT101C
- 凋亡试剂盒
Annexin V-FITC/PI Apoptosis Kit(贴壁细胞专用)(C6流式细胞仪专用)
- ¥860.00 – ¥1,510.00
-
- AP101
- 凋亡试剂盒
Annexin V-FITC/PI Apoptosis Kit(适用于除C6以外的流式细胞仪)
- ¥630.00 – ¥1,280.00
-
- AP101C
- 凋亡试剂盒
Annexin V-FITC/PI Apoptosis Kit (C6专用)
- ¥630.00 – ¥1,280.00