Temporal changes in milk proteomes reveal developing milk functions

J Proteome Res. 2012 Jul 6;11(7):3897-907. doi: 10.1021/pr3004002. Epub 2012 Jun 21.

Abstract

Human milk proteins provide essential nutrition for growth and development, and support a number of vital developmental processes in the neonate. A complete understanding of the possible functions of human milk proteins has been limited by incomplete knowledge of the human milk proteome. In this report, we have analyzed the proteomes of whey from human transitional and mature milk using ion-exchange and SDS-PAGE based protein fractionation methods. With a larger-than-normal sample loading approach, we are able to largely extend human milk proteome to 976 proteins. Among them, 152 proteins are found to render significant regulatory changes between transitional milk and mature milk. We further found that immunoglobulins sIgA and IgM are more abundant in transitional milk, whereas IgG is more abundant in mature milk, suggesting a transformation in defense mechanism from newborns to young infants. Additionally, we report a more comprehensive view of a complement system and associated regulatory apparatus in human milk, demonstrating the presence and function of a system similar to that found in the circulation but prevailed by alternative pathway in complement activation. Proteins involved in various aspects of carbohydrate metabolism are also described, revealing either a transition in milk functionality to accommodate carbohydrate-rich secretions as lactation progresses, or a potentially novel way of looking at the metabolic state of the mammary tissue. Lately, a number of extracellular matrix (ECM) proteins are found to be in higher abundance in transitional milk and may be relevant to the development of infants' gastrointestinal tract in early life. In contrast, the ECM protein fibronectin and several of the actin cytoskeleton proteins that it regulates are more abundant in mature milk, which may indicate the important functional role for milk in regulating reactive oxygen species.

MeSH terms

  • Actins / metabolism
  • Carbohydrate Metabolism
  • Chromatography, Ion Exchange
  • Complement System Proteins / metabolism
  • Extracellular Matrix Proteins
  • Female
  • Fibronectins / metabolism
  • Humans
  • Immunoglobulins / metabolism
  • Lactation*
  • Metabolic Networks and Pathways
  • Milk Proteins / chemistry
  • Milk Proteins / isolation & purification
  • Milk Proteins / metabolism*
  • Milk, Human / immunology
  • Milk, Human / metabolism*
  • Milk, Human / physiology
  • Protein Interaction Maps
  • Proteome / chemistry
  • Proteome / isolation & purification
  • Proteome / metabolism*
  • Reactive Oxygen Species / metabolism
  • Signal Transduction
  • Tandem Mass Spectrometry

Substances

  • Actins
  • Extracellular Matrix Proteins
  • Fibronectins
  • Immunoglobulins
  • Milk Proteins
  • Proteome
  • Reactive Oxygen Species
  • Complement System Proteins