Horm Metab Res 2020; 52(05): 336-339
DOI: 10.1055/a-1149-9347
Endocrine Research
© Georg Thieme Verlag KG Stuttgart · New York

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

1   School of Basic Pharmaceutical and Toxicological Sciences, University of Louisiana Monroe, Monroe, LA, USA
,
Mohammad S. Akhter
1   School of Basic Pharmaceutical and Toxicological Sciences, University of Louisiana Monroe, Monroe, LA, USA
,
Mohammad A. Uddin
1   School of Basic Pharmaceutical and Toxicological Sciences, University of Louisiana Monroe, Monroe, LA, USA
,
Khadeja-Tul Kubra
1   School of Basic Pharmaceutical and Toxicological Sciences, University of Louisiana Monroe, Monroe, LA, USA
,
Andrew V. Schally
2   Endocrine, Polypeptide, and Cancer Institute, Veterans Affairs Medical Center, University of Miami, Miami, FL, USA
› Author Affiliations

Funding: The study was supported by the R & D, Research Competitiveness Subprogram (RCS) of the Louisiana Board of Regents through the Board of Regents Support Fund (LEQSF(2019-22)-RD-A-26) (NB), the Faculty Research Support Program from the College of Pharmacy in ULM (NB), and the Medical Research Service of the Department of Veterans Affairs and University of Miami Miller School of Medicine (AVS).
Further Information

Publication History

received 17 February 2020

Publication Date:
13 May 2020 (online)

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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 H2O2-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.