An Antioxidant Role by Minocycline Via Enhancing the Activation of LKB1/AMPK Signaling in the Process of Cerebral Ischemia Injury.

Abstract

BACKGROUND:

LKB1/AMPK signaling pathway, as a metabolic checkpoint, is involved in the pathogenesis of cerebral ischemia injury. Minocycline, a tetracycline derivative, protects against cerebral ischemia via reducing inflammation, oxidative stress, and apoptosis. The aim of the study was to evaluate the influence of minocycline on oxidative biomarkers and LKB1/AMPK signaling pathway in Wistar rats with focal cerebral ischemia injury and to clarify the neuroprotective mechanism of minocycline against focal cerebral ischemia injury.

METHODS:

The focal cerebral ischemia injury of Wistar rats was established by inserting a thread into the left middle cerebral artery. 2,3,5-Triphenyltetrazolium chloride (TTC) staining was used to label infarct volume. The levels of MDA and LPO were measured with a biochemical assay. All other items were determined by Western blotting.

RESULTS:

Minocycline decreased cerebral infarct volume, but had no effects on neurological scores. Minocycline improved the biological activity of GPx-1/2, GSS and GR, while limited the GGT1 activity in the hippocampus of cerebral ischemia-reperfusion rats. Minocycline also elevated the biological activity of SOD and counteracted lipid peroxidation. Minocycline enhanced the activity of both LKB1 and the levels of the three AMPK subunits in the hippocampus of cerebral ischemia-reperfusion rats.

CONCLUSION:

Minocycline effectively inhibits oxidative stress via modulating antioxidative enzymes and activating the LKB1/AMPK signaling pathway in the process of acute cerebral infarct.

• Authors: Z Cai, C Wang, Y Chen, W He
• Journal: Current molecular medicine (Curr Mol Med) Vol. 18 Issue 3 Pg. 142-151 ( 2018) ISSN: 1875-5666 [Electronic] Netherlands
• PMID: 30198433 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright© Bentham Science Publishers; For any queries, please email at [email protected].

Chemical References

• Protein Serine-Threonine Kinases
• Stk11 protein, rat
• AMP-Activated Protein Kinase Kinases
• AMP-Activated Protein Kinases
• Minocycline

Topics

• AMP-Activated Protein Kinase Kinases
• AMP-Activated Protein Kinases (metabolism)
• Animals
• Brain Ischemia (drug therapy, enzymology, pathology)
• Male
• Minocycline (pharmacology)
• Oxidative Stress (drug effects)
• Protein Serine-Threonine Kinases (metabolism)
• Rats
• Rats, Wistar
• Signal Transduction (drug effects)