scholarly journals A Bioassay-Guided Fractionation of Rosemary Leaf Extract Identifies Carnosol as a Major Hypertrophy Inducer in Human Skeletal Muscle Cells

Nutrients ◽  
2021 ◽  
Vol 13 (12) ◽  
pp. 4190
Author(s):  
Sylvie Morel ◽  
Gérald Hugon ◽  
Manon Vitou ◽  
Marie Védère ◽  
Françoise Fons ◽  
...  

A good quality of life requires maintaining adequate skeletal muscle mass and strength, but therapeutic agents are lacking for this. We developed a bioassay-guided fractionation approach to identify molecules with hypertrophy-promoting effect in human skeletal muscle cells. We found that extracts from rosemary leaves induce muscle cell hypertrophy. By bioassay-guided purification we identified the phenolic diterpene carnosol as the compound responsible for the hypertrophy-promoting activity of rosemary leaf extracts. We then evaluated the impact of carnosol on the different signaling pathways involved in the control of muscle cell size. We found that activation of the NRF2 signaling pathway by carnosol is not sufficient to mediate its hypertrophy-promoting effect. Moreover, carnosol inhibits the expression of the ubiquitin ligase E3 Muscle RING Finger protein-1 that plays an important role in muscle remodeling, but has no effect on the protein synthesis pathway controlled by the protein kinase B/mechanistic target of rapamycin pathway. By measuring the chymotrypsin-like activity of the proteasome, we found that proteasome activity was significantly decreased by carnosol and Muscle RING Finger 1 inactivation. These results strongly suggest that carnosol can induce skeletal muscle hypertrophy by repressing the ubiquitin-proteasome system-dependent protein degradation pathway through inhibition of the E3 ubiquitin ligase Muscle RING Finger protein-1.

2004 ◽  
Vol 165 (6) ◽  
pp. 857-867 ◽  
Author(s):  
Limor Broday ◽  
Irina Kolotuev ◽  
Christine Didier ◽  
Anindita Bhoumik ◽  
Benjamin Podbilewicz ◽  
...  

Here, we describe a new muscle LIM domain protein, UNC-95, and identify it as a novel target for the RING finger protein RNF-5 in the Caenorhabditis elegans body wall muscle. unc-95(su33) animals have disorganized muscle actin and myosin-containing filaments as a result of a failure to assemble normal muscle adhesion structures. UNC-95 is active downstream of PAT-3/β-integrin in the assembly pathways of the muscle dense body and M-line attachments, and upstream of DEB-1/vinculin in the dense body assembly pathway. The translational UNC-95::GFP fusion construct is expressed in dense bodies, M-lines, and muscle–muscle cell boundaries as well as in muscle cell bodies. UNC-95 is partially colocalized with RNF-5 in muscle dense bodies and its expression and localization are regulated by RNF-5. rnf-5(RNAi) or a RING domain deleted mutant, rnf-5(tm794), exhibit structural defects of the muscle attachment sites. Together, our data demonstrate that UNC-95 constitutes an essential component of muscle adhesion sites that is regulated by RNF-5.


2011 ◽  
Vol 18 (9) ◽  
pp. 1500-1506 ◽  
Author(s):  
S S Devgan ◽  
O Sanal ◽  
C Doil ◽  
K Nakamura ◽  
S A Nahas ◽  
...  

2012 ◽  
Vol 287 (28) ◽  
pp. 24017-24025 ◽  
Author(s):  
Seung-Woo Hong ◽  
Dong-Hoon Jin ◽  
Jae-Sik Shin ◽  
Jai-Hee Moon ◽  
Young-Soon Na ◽  
...  

FEBS Letters ◽  
2011 ◽  
Vol 585 (24) ◽  
pp. 3856-3861 ◽  
Author(s):  
Bernhard Braun ◽  
Thorsten Pfirrmann ◽  
Ruth Menssen ◽  
Kay Hofmann ◽  
Hartmut Scheel ◽  
...  

2010 ◽  
Vol 12 (5) ◽  
pp. 658-666 ◽  
Author(s):  
Yun-Qiang Liu ◽  
Gang Bai ◽  
Hao Zhang ◽  
Dan Su ◽  
Da-Chang Tao ◽  
...  

Sign in / Sign up

Export Citation Format

Share Document