Neonatal Med.  2016 Feb;23(1):43-52. 10.5385/nm.2016.23.1.43.

Bee Venom Exerts Neuroprotective Effects on Neuronal Cells and Astrocytes under Hypoxic Conditions Through MAPK Signaling Pathways

• Lee EJ
• Kim BJ
• Jeong JE
• Chung HL
• Yang EK
• Kim WT

• KMID: 2312990
• DOI: http://doi.org/10.5385/nm.2016.23.1.43

Abstract

PURPOSE
Hypoxic-ischemic brain injuries influence the mechanisms of signal transduction, including mitogen-activated protein kinase (MAPK) that regulates gene expression through transcription factor activity. Several attempts have been made to use bee venom (BV) to treat neurological diseases. However, limited data are available for brain injuries such as neonatal hypoxic-ischemic encephalopathy (HIE) and neurodegenerative disorders. The purpose of this study was to investigate the neuroprotective effects of BV by determining the expression of activated MAPK pathways.
METHODS
We examined activation and cell viability in hypoxia (1% O2, 5% CO2, 94% N2) in low glucose-treated (H+low G) neuronal cells and astrocytes in the presence and absence of BV. After they were subjected to hypoxic conditions and treated with low glucose, the cells were maintained for 0, 6, 15, and 24 h under normoxic conditions.
RESULTS
Extracellular-signal-regulated kinases 1/2 (ERK1/2), p38 MAPK, and stress-activated protein kinases (SAPK)/Jun amino-terminal kinases (JNK) were activated in H+low G conditions. Particularly, phosphorylation of ERK1/2 was maximized 6 h after exposure to H+low G condition. BV specifically inhibited the phosphorylation of ERK1/2. However, BV had no effect on p38 MAPK or SAPK/JNK. In addition, BV improved neuronal cell and astrocytes viability following exposure to H+low G.
CONCLUSION
ERK inactivation is known to mediate protective effects in hypoxic brain injury. Taken together, these results suggest that treatment with BV may be helpful in reducing hypoxic injury in neonatal HIE through the ERK signaling pathway.

Keyword

Bee venom; Hypoxia; MAPK pathway; Astrocyte; Neuronal cell; Neuroprotective

MeSH Terms

Anoxia
Astrocytes*
Bee Venoms*
Bees*
Brain Injuries
Cell Survival
Gene Expression
Glucose
Hypoxia-Ischemia, Brain
Neurodegenerative Diseases
Neurons*
Neuroprotective Agents*
p38 Mitogen-Activated Protein Kinases
Phosphorylation
Phosphotransferases
Protein Kinases
Signal Transduction
Transcription Factors
Bee Venoms
Glucose
Neuroprotective Agents
Phosphotransferases
Protein Kinases
Transcription Factors
p38 Mitogen-Activated Protein Kinases