Nimodipine but Not Nifedipine Promotes Expression of Fatty Acid 2-Hydroxylase in a Surgical Stress Model Based on Neuro2a Cells.

Abstract

Nimodipine is well characterized for the management of aneurysmal subarachnoid hemorrhage and has been shown to promote a better outcome and less delayed ischemic neurological deficits. Animal and clinical trials show neuroprotective efficacy following nerve injuries. We showed a neuroprotective effect on Neuro2a cells. Subsequent microarray analysis revealed-among others-fatty acid 2-hydroxylase (FA2H) upregulated by nimodipine in vitro, which is a component of myelin synthesis. Differentiated Neuro2a cells were analyzed for nimodipine-mediated survival considering stress treatment in comparison to nifedipine-treatment. Cell survival was determined by measurement of LDH activity in the culture medium. Nimodipine decreased surgery-like stress-induced cell death of differentiated Neuro2a cells. Neuro2a cell culture was analyzed for changes in FA2H expression induced by nimodipine or nifedipine in surgery-like stress conditions. We analyzed expression levels of FA2H mRNA and protein by qPCR using fa2h specific primers or a FA2H-specific antibody in nimodipine or nifedipine non- and pre-treated Neuro2a cell culture, respectively. Nimodipine but not nifedipine increases FA2H protein levels and also significantly increases mRNA levels of FA2H in both undifferentiated and differentiated Neuro2a cells. Our findings indicate that higher expression of FA2H induced by nimodipine may cause higher survival of Neuro2a cells stressed with surgery-like stressors.

• Authors: Eva Herzfeld, Lea Speh, Christian Strauss, Christian Scheller
• Journal: International journal of molecular sciences (Int J Mol Sci) Vol. 18 Issue 5 (May 03 2017) ISSN: 1422-0067 [Electronic] Switzerland
• PMID: 28467360 (Publication Type: Journal Article)

Chemical References

• Calcium Channel Blockers
• Neuroprotective Agents
• RNA, Messenger
• Nimodipine
• Mixed Function Oxygenases
• fatty acid alpha-hydroxylase
• Nifedipine

Topics

• Animals
• Calcium Channel Blockers (pharmacology)
• Cell Death (drug effects)
• Cell Differentiation (drug effects)
• Cell Line
• Cell Survival (drug effects)
• Gene Expression
• Heat-Shock Response (drug effects)
• Mice
• Mixed Function Oxygenases (genetics, metabolism)
• Myelin Sheath (metabolism)
• Neuroprotective Agents (pharmacology)
• Neurosurgical Procedures (adverse effects)
• Nifedipine (pharmacology)
• Nimodipine (pharmacology, therapeutic use)
• Oxidative Stress (drug effects)
• RNA, Messenger (genetics)
• Stress, Mechanical
• Up-Regulation