Detection of renal and urinary tract proteins before and after spaceflight.
BACKGROUND
The recent evolution of genomics and subsequently proteomics offers a major advance in the ability to understand individual human variation in disease and the molecular level changes induced by certain environmental exposures. This original study examines urinary proteome composition to enable the understanding of molecular homeostatic mechanisms in spaceflight and presents the potential for early detection of subclinical disease, microgravity risk mitigation strategies, and countermeasure development for exploration-class missions.


METHODS
The urinary proteome composition of six Russian cosmonauts (men, ages 35-51) who flew long-duration missions of 169-199 d was determined 30 d before flight and compared to repeat studies 1 and 7 d postflight.


RESULTS
There were 430 proteins identified. Of those, 15 proteins originated in the renal tissues. Of the 15 urinary proteins, 10 were consistently present in the urine. However, the presence of five of the urinary proteins--neutral endopeptidase (NEP), afamin (AFAM), aquaporin-2 (AQP2), aminopeptidase A (AMPE), and dipeptidyl peptidase 4 (DPP4)--was dependent on spaceflight exposure.


CONCLUSIONS
Proteomic investigation of pre- and postflight urine and bioinformation approaches to proteome analysis provide important data relative the mechanism of kidney function in spaceflight. In this initial study, we determined that the evaluation of urinary proteins may help investigators understand changes that are occurring in microgravity. Once additional ground-based and in-flight data are collected, it is feasible to develop targeted studies for tracking specific spaceflight related changes, determine countermeasure and risk-mitigation effectiveness, and possibly detect subclinical disease in flight crewmembers.
Institute of Medicobiologic Problems, Russian Federation State Scientific Research Center Russian Academy of Sciences, Moscow, Russia.
Lyudmila Kh
LKh
Pastushkova
Kirill S
KS
Kireev
Alexei S
AS
Kononikhin
Vladimir A
VA
Ivanisenko
Irina M
IM
Larina
Evgeny N
EN
Nikolaev
D000328:Adult; D051399:Aquaporin 2 / Q000652:urine; D001798:Blood Proteins / Q000652:urine; D002352:Carrier Proteins / Q000652:urine; D002853:Chromatography, Liquid; D018819:Dipeptidyl Peptidase 4 / Q000652:urine; D004815:Epidermal Growth Factor / Q000652:urine; D043384:Glutamyl Aminopeptidase / Q000652:urine; D006023:Glycoproteins / Q000652:urine; D006801:Humans; D007704:Kininogens / Q000652:urine; D026561:Low Density Lipoprotein Receptor-Related Protein-2 / Q000032:analysis; D008297:Male; D013058:Mass Spectrometry; D008875:Middle Aged; D015260:Neprilysin / Q000652:urine; D053495:Osteopontin / Q000652:urine; D011956:Receptors, Cell Surface / Q000032:analysis; D012709:Serum Albumin; D000075462:Serum Albumin, Human; D013026:Space Flight; D020840:Tissue Kallikreins / Q000652:urine; D058949:Uromodulin / Q000652:urine; D019010:Vascular Cell Adhesion Molecule-1 / Q000652:urine; D023083:beta-Defensins / Q000652:urine
C088246:AFM protein, human; D051399:Aquaporin 2; D001798:Blood Proteins; D002352:Carrier Proteins; D006023:Glycoproteins; D007704:Kininogens; D026561:Low Density Lipoprotein Receptor-Related Protein-2; D011956:Receptors, Cell Surface; D012709:Serum Albumin; D058949:Uromodulin; D019010:Vascular Cell Adhesion Molecule-1; D023083:beta-Defensins; C029486:intrinsic factor-cobalamin receptor; C026080:plasma protein Z; D053495:Osteopontin; D004815:Epidermal Growth Factor; D043384:Glutamyl Aminopeptidase; C042807:DPP4 protein, human; D018819:Dipeptidyl Peptidase 4; D020840:Tissue Kallikreins; D015260:Neprilysin; D000075462:Serum Albumin, Human