Chrono-Proteomics of Human Saliva: Variations of the Salivary Proteome during Human Development

An important contribution to the
variability of any proteome is
given by the time dimension that should be carefully considered to
define physiological modifications. To this purpose, whole saliva
proteome was investigated in a wide age range. Whole saliva was collected
from 17 preterm newborns with a postconceptional age at birth of 178–217
days. In these subjects sample collection was performed serially starting
immediately after birth and within about 1 year follow-up, gathering
a total of 111 specimens. Furthermore, whole saliva was collected
from 182 subjects aged between 0 and 17 years and from 23 adults aged
between 27 and 57 years. The naturally occurring intact salivary proteome
of the 316 samples was analyzed by low- and high-resolution HPLC–ESI–MS
platforms. Proteins peculiar of the adults appeared in saliva with
different time courses during human development. Acidic proline-rich
proteins encoded by PRH2 locus and glycosylated basic
proline-rich proteins encoded by PRB3 locus appeared
following 180 days of postconceptional age, followed at 7 months (±2
weeks) by histatin 1, statherin, and P–B peptide. The other
histatins and acidic proline-rich proteins encoded by PRH1 locus appeared in whole saliva of babies from 1 to 3 weeks after
the normal term of delivery, S-type cystatins appeared at 1 year (±3
months), and basic proline-rich proteins appeared at 4 years (±1
year) of age. All of the proteinases involved in the maturation of
salivary proteins were more active in preterm than in at-term newborns,
on the basis of the truncated forms detected. The activity of the
Fam20C kinase, involved in the phosphorylation of various proteins,
started around 180 days of postconceptional age, slowly increased
reaching values comparable to adults at about 2 years (±6 months)
of age. Instead, MAPK14 involved in the phosphorylation of S100A9
was fully active since birth also in preterm newborns.