Neurosteroid inhibition of cell death

The American Journal of Physiology
S L WatersR G Schnellmann

Abstract

Diverse gamma-aminobutyric acid (GABAA) receptor modulators exhibited novel cytoprotective effects and mechanisms of action in rabbit renal proximal tubules subjected to mitochondrial inhibition (antimycin A) or hypoxia. Cytoprotective potencies (50% effective concentration, EC50) were 0.3 nM allopregnanolone (AP) > 0.4 nM 17 alpha-OH-allopregnanolone (17 alpha-OH-AP) > 30 nM dehydroepiandrosterone sulfate (DHEAS) = 30 nM pregnenolone sulfate (PS) > 500 nM pregnenolone (PREG) > 30 microM muscimol > 10 mM GABA following antimycin A exposure. Maximal protection with AP and 17 alpha-OH-AP was 70%, whereas DHEAS, PS, PREG, and muscimol produced 100% cytoprotection. Experiments with AP, PS, and muscimol revealed the return of mitochondrial function and active Na+ transport following hypoxia/reoxygenation. Muscimol inhibited the antimycin A-induced influx of both extracellular Ca2+ and Cl- that occurs during the late phase of cell injury, whereas the neurosteroids only inhibited influx of Cl-. Radioligand binding studies with AP and PS did not reveal a specific binding site; however, structural requirements were observed for cytoprotective potency and efficacy. In conclusion, we suggest that the GABAA receptor modulators muscimol and...Continue Reading

References

Jun 1, 1992·American Journal of Kidney Diseases : the Official Journal of the National Kidney Foundation·S N HeymanS Rosen
Aug 1, 1991·Kidney International·S N HeymanF H Epstein
Sep 1, 1990·In Vitro Cellular & Developmental Biology : Journal of the Tissue Culture Association·D P RodeheaverR G Schnellmann
Mar 1, 1991·The American Journal of Physiology·W R JacobsL J Mandel
Feb 1, 1991·Cryobiology·D C MarshJ H Southard
Apr 1, 1991·Kidney International·P SilvaF H Epstein
Dec 1, 1990·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·J M WeinbergJ A Davis
Feb 1, 1990·Journal of Neurochemistry·S L Erdö, J R Wolff
Mar 1, 1995·The Journal of Pharmacy and Pharmacology·Q LiM S Yates
Dec 1, 1994·Journal of Cardiovascular Electrophysiology·S Sorota
Mar 1, 1996·Kidney International·I Nissim, J M Weinberg
Sep 1, 1996·Journal of Pharmacological and Toxicological Methods·J H Moran, R G Schnellmann
Feb 1, 1956·The Biochemical Journal·A LEAF

❮ Previous
Next ❯

Citations

Feb 8, 2000·American Journal of Physiology. Renal Physiology·X Meng, W B Reeves
Jan 23, 2021·Molecular and Cellular Endocrinology·Melina A PagottoLiliana A Monasterolo

❮ Previous
Next ❯

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.