Vitamin K2 protects PC12 cells against Aβ (1-42) and H 2 O 2-induced apoptosis via p38 MAP kinase pathway

Nutr Neurosci. 2020 May;23(5):343-352. doi: 10.1080/1028415X.2018.1504428. Epub 2018 Jul 30.

Abstract

Alzheimer's is an age-related disease with a hallmark of progressive loss of memory formation followed by a damage in the brain function due to the neural degeneration and extracellular beta-amyloid (Aβ) plaques accumulation. This study examines the protective effects of vitamin K2 on toxicity induced by (Aβ) (1-42) and H2O2 in PC12 cells as an appropriate model of Alzheimer's cell damage. PC12 cells pretreated with vitamin K2 (5-200 μM) for 4, 24 and 48 h, and exposed to either Aβ (25 µM) for 48 h or H2O2 (150 µM) for 24 h. Then the protective, antioxidant and anti-apoptotic effects of vitamin K2 in PC12 cells were investigated. Vitamin K2 pretreatment (5-200 μM) significantly decreased the Aβ (1-42) and H2O2 cytotoxicity. In addition, vitamin K2 could attenuate reactive oxygen species (ROS) level after exposure of cells to H2O2 for 24 h and Aβ (1-42) for 48 h. Cell apoptosis significantly increased following application of Aβ (1-42) (25 μM) and H2O2 (150 µM) compared to control. However, flow cytometry histograms of PI-stained cells after pretreatment with vitamin K2 (20 and 50 μM) showed significantly reduced apoptosis. Vitamin K2 increased the amount of glutathione after exposure of cells to H2O2 for 24 h and Aβ (1-42) for 48 h. Western blot analysis of PC12 cells showed that 25 μM Aβ (1-42) and 150 µM H2O2 treatment could increase Bax, PARP cleavage, Phospho-p38 MAPK. Moreover, the activated form of caspase 3 proteins led to the reduction in the Bcl-2. Real-time PCR of PC12 cells showed that 150 µM H2O2 treatment increased the ratio of Bax/Bcl-2 while vitamin K2 (20 and 50 μM) reduced the rate. According to these findings, it seems that vitamin K2 possess anti-apoptotic and antioxidant effects and suggests that vitamin K2 may be a valuable protective candidate against the progression of Alzheimer's disease via inactivating p38 MAP kinase pathway.

Keywords: Alzheimer’s disease; Antioxidant; Beta-amyloid; Vitamin K2.

MeSH terms

  • Amyloid beta-Peptides / toxicity*
  • Animals
  • Apoptosis / drug effects*
  • Cell Survival / drug effects
  • Hydrogen Peroxide / toxicity*
  • MAP Kinase Signaling System / drug effects*
  • Neuroprotective Agents / administration & dosage*
  • PC12 Cells
  • Peptide Fragments / toxicity*
  • Rats
  • Reactive Oxygen Species / metabolism
  • Vitamin K 2 / administration & dosage*

Substances

  • Amyloid beta-Peptides
  • Neuroprotective Agents
  • Peptide Fragments
  • Reactive Oxygen Species
  • amyloid beta-protein (1-42)
  • Vitamin K 2
  • Hydrogen Peroxide