Issue 6, 2014

s-Methyl cysteine enhanced survival of nerve growth factor differentiated PC12 cells under hypoxic conditions

Abstract

A nerve growth factor-differentiated PC12 cell line was used to investigate the protective effects of s-methyl cysteine (SMC) at 1, 2, 4, and 8 μM under oxygen–glucose deprivation (OGD) conditions. OGD decreased the cell viability. However, SMC pre-treatments at 2, 4 and 8 μM improved the cell viability, decreased cleaved caspase-3 and Bax expression, and reserved Bcl-2 expression. Furthermore, SMC maintained the mitochondrial membrane potential, lowered the intracellular Ca2+ concentration and DNA fragmentation, and decreased the activity and expression of caspase-3 and caspase-8. OGD increased the reactive oxygen species (ROS) and 3-nitrotyrosine production, decreased glutathione peroxide (GPX) and glutathione reductase (GR) activities and the expression, enhanced nitric oxide synthase (NOS) activity and inducible NOS (iNOS) expression. SMC pre-treatments at 2, 4 and 8 μM lowered the ROS and 3-nitrotyrosine formation, maintained GPX and GR activities and expression, and decreased NOS activity and iNOS expression. OGD up-regulated hypoxia-inducible factor (HIF)-1α, nuclear transcription factor kappa (NF-κ) B p50, NF-κB p65 and p-p38 expression. SMC pre-treatments at 1–8 μM lowered HIF-1α expression and decreased p38 phosphorylation. SMC at 2, 4 and 8 μM suppressed the protein expression of NF-κB p50 and NF-κB p65. When YC-1 (HIF-1α inhibitor), pyrrolidine dithiocarbamate (NF-κB inhibitor) or SB203580 (p38MAPK inhibitor) were used to block the activation of HIF-1α, NF-κB and p38, SMC pre-treatments did not affect the protein expression of HIF-1α, NF-κB and p-p38. These results indicated that SMC was a potent neuro-protective agent.

Graphical abstract: s-Methyl cysteine enhanced survival of nerve growth factor differentiated PC12 cells under hypoxic conditions

Article information

Article type
Paper
Submitted
19 Dec 2013
Accepted
19 Feb 2014
First published
21 Feb 2014

Food Funct., 2014,5, 1125-1133

Author version available

s-Methyl cysteine enhanced survival of nerve growth factor differentiated PC12 cells under hypoxic conditions

C. Liu, T. Hsia and M. Yin, Food Funct., 2014, 5, 1125 DOI: 10.1039/C3FO60689A

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