Next Article in Journal
Role of Milk-Derived Antibacterial Peptides in Modern Food Biotechnology: Their Synthesis, Applications and Future Perspectives
Next Article in Special Issue
In Silico Studies on Compounds Derived from Calceolaria: Phenylethanoid Glycosides as Potential Multitarget Inhibitors for the Development of Pesticides
Previous Article in Journal
Probing the Occurrence of Soluble Oligomers through Amyloid Aggregation Scaling Laws
Previous Article in Special Issue
Flavonoids as Putative Epi-Modulators: Insight into Their Binding Mode with BRD4 Bromodomains Using Molecular Docking and Dynamics
Open AccessArticle

A Marine Diterpenoid Modulates the Proteasome Activity in Murine Macrophages Stimulated with LPS

1
Centro de Biología Celular y Molecular de Enfermedades, Instituto de Investigaciones Científicas y Servicios de Alta Tecnología (INDICASAT AIP),Edificio 219, Ciudad del Saber, 0801 Panamá, Panamá
2
Facultad de Ciencias de la Salud Dr. William C. Gorgas, Universidad Latina de Panamá, 0801 Panamá, Panamá
3
Centro de Biodiversidad y Descubrimiento de Drogas, INDICASAT AIP, Edificio 219, Ciudad del Saber, 0801 Panamá, Panamá
*
Authors to whom correspondence should be addressed.
Biomolecules 2018, 8(4), 109; https://doi.org/10.3390/biom8040109
Received: 13 August 2018 / Revised: 14 September 2018 / Accepted: 1 October 2018 / Published: 5 October 2018
The proteasome is an intracellular complex that degrades damaged or unfolded proteins and participates in the regulation of several processes. The immunoproteasome is a specialized form that is expressed in response to proinflammatory signals and is particularly abundant in immune cells. In a previous work, we found an anti-inflammatory effect in a diterpenoid extracted from the octocoral Pseudopterogorgia acerosa, here called compound 1. This compound prevented the degradation of inhibitor κB α (IκBα) and the subsequent activation of nuclear factor κB (NFκB), suggesting that this effect might be due to inhibition of the ubiquitin-proteasome system. Here we show that compound 1 inhibits the proteasomal chymotrypsin-like activity (CTL) of murine macrophages in the presence of lipopolysaccharide (LPS) but not in its absence. This effect might be due to the capacity of this compound to inhibit the activity of purified immunoproteasome. The compound inhibits the cell surface expression of major histocompatibility complex (MHC)-I molecules and the production of proinflammatory cytokines induced by LPS in vitro and in vivo, respectively. Molecular docking simulations predicted that compound 1 selectively binds to the catalytic site of immunoproteasome subunits β1i and β5i, which are responsible for the CTL activity. Taken together these findings suggest that the compound could be a selective inhibitor of the immunoproteasome, and hence could pave the way for its future evaluation as a candidate for the treatment of inflammatory disorders and autoimmune diseases. View Full-Text
Keywords: marine diterpenoid; proteasome inhibitors; immunoproteasome marine diterpenoid; proteasome inhibitors; immunoproteasome
Show Figures

Graphical abstract

MDPI and ACS Style

González, Y.; Doens, D.; Cruz, H.; Santamaría, R.; Gutiérrez, M.; Llanes, A.; Fernández, P.L. A Marine Diterpenoid Modulates the Proteasome Activity in Murine Macrophages Stimulated with LPS. Biomolecules 2018, 8, 109.

Show more citation formats Show less citations formats
Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Article Access Map by Country/Region

1
Search more from Scilit
 
Search
Back to TopTop