1. GHRH Antagonists Protect Against Hydrogen Peroxide-Induced Breakdown of Brain Microvascular Endothelium Integrity.
- Author
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Barabutis N, Akhter MS, Uddin MA, Kubra KT, and Schally AV
- Subjects
- Actins metabolism, Endothelium drug effects, HeLa Cells, Humans, Sermorelin analogs & derivatives, Sermorelin pharmacology, Tumor Suppressor Protein p53 metabolism, Brain blood supply, Endothelium pathology, Growth Hormone-Releasing Hormone antagonists & inhibitors, Hydrogen Peroxide toxicity, Microvessels pathology, Neuroprotective Agents pharmacology
- 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 H
2 O2 -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., Competing Interests: The authors declare that they have no conflict of interest., (© Georg Thieme Verlag KG Stuttgart · New York.)- Published
- 2020
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