GHRH Antagonists Protect Against Hydrogen Peroxide-Induced Breakdown of Brain Microvascular Endothelium Integrity.

Hormone and metabolic research = Hormon- und Stoffwechselforschung = Hormones et metabolisme2020PMID: 32403147

Plain Language Summary

This study found that the GHRH receptor blocker MIA-602 protects the blood-brain barrier from damage caused by hydrogen peroxide, a marker of oxidative stress. MIA-602 strengthened the barrier by activating the protective protein P53, deactivating a protein called cofilin that destabilizes cell structure, and suppressing the inflammatory RhoA pathway. These results suggest GHRH antagonists could potentially help treat conditions involving blood-brain barrier breakdown, such as Parkinson's and Alzheimer's diseases.

Abstract

Growth hormone releasing hormone is a hypothalamic neuropeptide, which regulates the release of growth hormone from the anterior pituitary gland. Growth hormone releasing hormone antagonists are anticancer agents, associated with strong anti-inflammatory activities. In the present study, we investigated the effects of the GHRH antagonist MIA-602 in the integrity of the brain microvascular endothelium in vitro. Our observations suggest that MIA-602 protects against the HO-induced breakdown of the brain endothelium and enhances its integrity by inducing P53, deactivating cofilin, and suppressing the RhoA inflammatory pathway. Thus, GHRH antagonists may offer an exciting possibility for the treatment of pathologies related to the blood brain barrier dysfunction, including the Parkinson's and Alzheimer's diseases.

Authors

Barabutis, Nektarios; Akhter, Mohammad S; Uddin, Mohammad A; Kubra, Khadeja-Tul; Schally, Andrew V