Method for replacing biomarkers of protein kinetics from tissue samples by biomarkers of protein kinetics from body fluids after isotopic labeling in vivo

摘要

Provided herein are method for measuring the rate of synthesis, breakdown, transport, or other kinetic parameters of a protein in a tissue of medical interest, without requiring physical sampling of the tissue, by a measurement of the protein in a body fluid. Methods may include selecting one or more target proteins in a tissue; administering an isotope-labeled molecule to a subject for a period of time sufficient for said isotope-labeled molecule to enter into and label the one or more target proteins to produce one or more isotope-labeled target proteins; collecting a volume of a body fluid, wherein the volume comprises one or more isotope-labeled target proteins that escaped or were released from the tissue; enriching or isolating the one or more isotope-labeled target proteins from the volume; performing a mass spectrometric measurement of the isotopic content, rate of incorporation, and/or pattern or rate of change in isotopic content and/or pattern of isotope labeling of the one or more enriched or isolated isotope-labeled target proteins; and calculating at least one kinetic parameter of the one or more enriched or isolated isotope-labeled target proteins, where the kinetic parameter of the one or more isotope-labeled target proteins from the volume of a body fluid reflects the corresponding kinetic parameter of the one or more target proteins in the tissue; and inferring the at least one kinetic parameter of the one or more target proteins in the tissue based on the corresponding at least one kinetic parameter of the one or more target proteins in the body fluid.