Towards an Understanding of Biological Role of Colostrinin Peptides

Abstract

The aim of this study was to elucidate the structure and possible function of colostrinin, also known as a proline rich polypeptide (PRP). The molecular weight of colostrinin was originally determined by gel filtration to be 17,200 daltons. In the presence of guanidinum chloride, however, the molecular weight was found to be about 6,000 daltons. Further studies utilizing high-performance liquid chromatography (HPLC) and mass spectroscopy revealed that colostrinin is a complex consisting of many low molecular-weight polypeptides. A total of 32 peptides were isolated from the original colostrinin preparation by HPLC and subjected to the N-terminal sequence analysis. The results of sequence analysis revealed significant homology of the peptides to three protein precursors: annexin, beta-casein, and a hypothetical beta-casein homolog. In addition, the sequence of several peptides showed no significant homology to any specific protein in the current GenBank database. The synthetic peptides of various lengths representing the N-terminal sequence of the colostrinin peptides were made to study some biological effects. Here we report that colostrinin and some of its component peptides are potent inducers of leukocyte proliferation and of certain cytokines. Also, a series of monospecific antibodies were produced in rabbits against the synthetic peptides. The antibodies were used to study the kinetic of antigen reduction in colostrum and mature milk following lambing. A threefold decrease was common for most antigens studied over the period of 72 h. Based on the results of these studies we postulate that colostrinin represents a diverse group of peptides produced in the mammary gland of mammals for the development of the optimal physiologic responses in offspring. Also, it is hoped that the beneficial use of colostrinin in Alzheimer's Disease (AD), recently reported elsewhere, will revive interest in its clinical application for treatment and/or prophylaxis of many age-related disorders.

Colostrinin Decreases Hypersensitivity and Allergic Responses to Common Allergens

“…CLN is a mixture of low-molecular-weight, proline-rich peptides [2, 4, 5] that has been administered to individuals with age-associated dementia [12,13,14]. Whether CLN induces allergic responses or modulates responses to other allergens has never been investigated.…”

“…CLN is purified from pre-milk fluid (colostrum) collected from mothers during the first 24 h after giving birth [1,2,3,4,5]. It has been shown that CLN is an important immune modulator that induces maturation and differentiation of murine thymocytes [3, 6], promotes peripheral blood leukocyte proliferation and induces cytokine production [3, 7].…”

Colostrinin-Driven Neurite Outgrowth Requires p53 Activation in PC12 Cells

“…CLN was purified from ovine (CLN O ) or bovine (CLN B ) colostrum as described previously (Janusz et al, 1974;Kruzel et al, 2001Kruzel et al, , 2004. Two-dimensional acrylamide gel electrophoresis showed that the protein (3-25 kD polypeptides) composition of CLN O and CLN B was nearly identical in size and number (Boldogh et al, unpublished data).…”

Clinical applications of bioactive milk components

“…144 During a preliminary trial of the putative immunomodulatory effects of proline-rich polypeptide, unexpected psychostimulation was observed in human subjects. 145 Subsequently, trials in rats demonstrated that administration of clostrinin, a specific proline-rich polypeptide preparation, promoted spatial learning and improved incidental memory, 146 leading to the proposal that proline-rich polypeptide attenuates neurologic decline.…”