Oral Ingestion of Collagen Hydrolysate Leads to the Transportation of Highly Concentrated Gly-Pro-Hyp and Its Hydrolyzed Form of Pro-Hyp into the Bloodstream and Skin.

Collagen hydrolysate is a well-known dietary supplement for the treatment of skin aging; however, its mode of action remains unknown. Previous studies have shown that the oral ingestion of collagen hydrolysate leads to elevated levels of collagen-derived peptides in the blood, but whether these peptides reach the skin remains unclear. Here, we analyzed the plasma concentration of collagen-derived peptides after ingestion of high tripeptide containing collagen hydrolysate in humans. We identified 17 types of collagen-derived peptides transiently, with a particular enrichment in Gly-Pro-Hyp. This was also observed using an in vivo mouse model in the plasma and skin, albeit with a higher enrichment of Pro-Hyp in the skin. Interestingly, this Pro-Hyp enrichment in the skin was derived from Gly-Pro-Hyp hydrolysis, as the administration of pure Gly-Pro-Hyp peptide led to similar results. Therefore, we propose that functional peptides can be transferred to the skin by dietary supplements of collagen.

Rapid degradation of cyclooxygenase-1 and hematopoietic prostaglandin D synthase through ubiquitin-proteasome system in response to intracellular calcium level.

Cyclooxygenase (COX)-1 and hematopoietic prostaglandin (PG) D synthase (H-PGDS) proteins, which are both involved in the arachidonate cascade, were stable in human megakaryocytic MEG-01 cells. In contrast, once the intracellular calcium level was increased by treatment with a calcium ionophore, both protein levels rapidly decreased with a half-life of less than 30 and 120 min for COX-1 and H-PGDS, respectively. In the presence of a proteasome inhibitor, COX-1 and H-PGDS proteins accumulated within 10 and 30 min, respectively, and concurrently appeared as the high-molecular-mass ubiquitinated proteins within 30 and 60 min, respectively, after an increase in the intracellular calcium level. The ubiquitination of these proteins was also observed when ADP, instead of a calcium ionophore, was used as an inducer to elevate the intracellular calcium level. When the entry of calcium ion into the cells was inhibited by ethylene glycol tetraacetic acid (EGTA), the ubiquitination of COX-1 and H-PGDS was clearly suppressed; and the addition of CaCl(2) to the medium cleared the EGTA-mediated suppression of the ubiquitination. These results indicate that COX-1 and H-PGDS were rapidly ubiquitinated and degraded through the ubiquitin-proteasome system in response to the elevation of the intracellular calcium level.