Bovine α-Lactalbumin Stimulates Mucus Metabolism in Gastric Mucosa

Abstract

Bovine alpha-lactalbumin (alpha-LA), a major milk protein, exerts strong gastroprotective activity against rat experimental gastric ulcers induced by ethanol or stress. To elucidate the mechanisms underlying this activity, the influence of alpha-LA on gastric mucus metabolism was investigated in vitro and in vivo. For the in vitro study, RGM1 cells (a rat gastric epithelial cell line) were selected for observation of the direct activity of alpha-LA on gastric mucosal cells and cultured in the presence of either alpha-LA or ovalbumin (OVA), a reference protein showing no gastroprotective activity. Amounts of synthesized and secreted mucin, a major component of mucus, were determined using [3H]glucosamine as a tracer, and prostaglandin E2 (PGE2) levels in the culture medium were determined by RIA. For the in vivo study, the thickness of the mucus gel layer, a protective barrier for gastric mucosa, was evaluated histochemically in rat gastric mucosa. alpha-Lactalbumin (3 mg/mL) significantly stimulated mucin synthesis and secretion in RGM1 cells and also increased PGE2 levels in the culture medium. In contrast, OVA showed no enhancing effects under identical conditions. Neither indomethacin, a cyclo-oxygenase inhibitor, nor AH23848, a prostaglandin EP4 receptor antagonist, affected alpha-LA-induced enhancement of mucin synthesis and secretion. In vivo, oral administration of alpha-LA (300 mg/kg x 3 times/d x 7 d) increased the thickness of the mucus gel layer in rats. These results indicate that alpha-LA fortifies the mucus gel layer by stimulating mucin production and secretion in gastric mucus-producing cells, and that this enhancing effect is independent of endogenous PGE2. Comparison of the efficacy of alpha-LA with OVA suggests that the activities observed in RGM1 cells are closely related to the gastroprotective effects in rat gastric ulcer models. In conclusion, alpha-LA stimulates mucus metabolism, and this action may be responsible for its gastroprotective activity.

Antiulcerogenic activity of peptide concentrates obtained from hydrolysis of whey proteins by proteases from Cynara cardunculus

“…There is a distinct behaviour of cardosins upon the two dominant proteins in whey: a-La is highly susceptible to those enzymes, whereas b-lactoglobulin is not hydrolyzed to a significant extent (Barros & Malcata, 2006). This realization suggests that any peptides in WPC that may account for protection against gastric injury originated in a-La, which is in agreement with the claims by Matsumoto et al (2001), Mezzaroba et al (2006) and Ushida, Shimokawa, Toida, Matsui, and Takase (2007). On the other hand, previous studies encompassing a-La and its pancreatin hydrolyzate indicated a 32e50% decrease in ULI when two consecutive doses of 200 mg kg À1 bw were administered to rats (Matsumoto et al, 2001), whereas Mezzaroba et al (2006) described an 82% reduction under similar conditions.…”

Chronic Administration of Bovine Milk-Derived α-Lactalbumin Improves Glucose Tolerance <i>via</i> Enhancement of Adiponectin in Goto–Kakizaki Rats with Type 2 Diabetes

“…15) Additionally, it has been reported that α-lactalbumin fortifies the mucus gel layer by stimulating mucin production and secretion in gastric mucus-producing cells, and that this enhancing effect is independent of endogenous PGE2. 29) These results indicated that α-lactalbumin reduces the gastrointestinal side-effects.…”

Novel Functions of Bovine Milk-Derived .ALPHA.-Lactalbumin: Anti-nociceptive and Anti-inflammatory Activity Caused by Inhibiting Cyclooxygenase-2 and Phospholipase A2

“…20) aLA stimulates mucin synthesis and secretion in mucusproducing cells and induces increased thickness of the mucus gel layer in the gastric mucosa, suggesting that stimulation of mucus metabolism by aLA contributes to its gastroprotective actions.…”