Casein-derived phosphopeptides disrupt tight junction integrity, and precipitously dry up milk secretion in goats

Shamay, Avi; Shapiro, Fira; Mabjeesh, S.J.; Silanikove, Nissim

doi:10.1016/s0024-3205(02)01527-8

Cited by 72 publications

(74 citation statements)

References 19 publications

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“…The present results are consistent with previous findings that have shown that the inflammatory response induced by LPS disrupts tight junction integrity as reflected by changes in Na 1 and K 1 concentrations in milk (Shamay et al, 2002 and and increases the secretion of soluble constituents of the innate immune system IbeaghaAwemu et al, 2010), including the secretion of albumin from mammary epithelial cells .…”

Section: Lps Challenge Is Reflected By Accumulation Of Inflammatory Isupporting

confidence: 93%

“…The simultaneous reduction in milk quality and milk secretion in infected glands is related to the activation of plasminogen activator (PA), plasminogen (PG) and plasmin (PL)-derived active peptides from milk b-casein (Silanikove et al, 2000(Silanikove et al, and 2009aShamay et al, 2002 and. Enzymes linked to the metabolism of nitric oxide (NO) have also been shown recently to considerably affect the milk composition of inflamed mammary glands (Silanikove et al, , 2009a(Silanikove et al, and 2009b.…”

Section: Introductionmentioning

confidence: 99%

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Lipopolysaccharide challenge of the mammary gland in cows induces nitrosative stress that impairs milk oxidative stability

Silanikove

Rauch-Cohen

Shapiro

et al. 2012

Animal

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The aim of this work was to study the effects of mastitis induced by intramammary lipopolysaccharide (LPS) challenge on milk oxidative stability, as well as to understand the underlying biochemical processes that cause such changes. LPS challenge was associated with nitric oxide burst from the surrounding mammary epithelial cells and consequently induced nitrosative stress that was induced by the formation of NO 2 d from nitrite by lactoperoxidase. This response was associated with an , 3-fold increased formation of hazardous compounds: nitrotyrosines, carbonyls and lipid peroxides. We sustained the involvement of xanthine oxidase as a major source of hydrogen peroxide. In consistent with previous findings, catalase has been shown to play a major role in modulating the nitrosative stress by oxidizing nitrite to nitrate. The current hygienic quality criteria cannot detect mixing of low-quality milk, such as milk with high somatic cells, and nitrite with high-quality milk. Thus, development of an improved quality control methodology may be important for the production of high-quality milk.Keywords: milk, cow, mastitis, NO and NO 2 d, plasmin system Implication In this study, we show that intramammary treatment with lipopolysaccharide induced nitric oxide burst that was associated with nitrosative stress that reflected the formation of hazardous compounds in milk: nitrotyrosines, carbonyls and lipid peroxides. These changes were associated with impairment in milk quality. Currently, very little is known about the presence of oxidative substances in commercial milk and their industrial and health implications. As mastitis is a prevalent problem in the dairy industry, this study stresses the importance of gaining further information on the effect of different forms of mastitis on milk composition.

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Section: Lps Challenge Is Reflected By Accumulation Of Inflammatory Isupporting

confidence: 93%

Section: Introductionmentioning

confidence: 99%

Lipopolysaccharide challenge of the mammary gland in cows induces nitrosative stress that impairs milk oxidative stability

Silanikove

Rauch-Cohen

Shapiro

et al. 2012

Animal

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“…Similarly, when milk stored in the mammary gland was diluted with an isosmotic sucrose solution, the milk secretion rate increased suggesting that dilution of a chemical inhibitor occurred [9]. Casein phosphopeptides derived from activation of the milk protease plasmin disrupt TJ and inhibit milk secretion during extended periods of milk accumulation in goats and cows [10,11,61], although the exact mechanism by which this occurs remains to be determined.…”

Section: Discussionmentioning

confidence: 99%

“…Studies indicate that the increased milk production response to more frequent milk removal was due to removal of a chemical inhibitor in milk of lactating goats [8,9] or casein-derived phosphopeptides causing local disruption of tight junction (TJ) integrity and inhibition of milk secretion in goats and cows [10,11]. The local synthesis of serotonin has also been implicated to disrupt TJ and regulate mammary function in cows [12,13].…”

Section: Introductionmentioning

confidence: 99%

Induced Physical Distension of Rat Mammary Glands Accelerates the Onset of Apoptosis and Involution

Phyn¹,

Davis²,

Dobson³

et al. 2017

J Cell Signal

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Objective: Weaning is a process that results in a reduction in milk secretion, an increase in mammary epithelial cell (MEC) apoptosis, and involution of the mammary gland. The local mechanisms initiating MEC apoptosis and involution are unclear, although the physical morphology of the MEC may influence cell-cell and cell-extracellular matrix communication and thus may alter function. This study examined the effect of physical distension of alveoli on the early molecular events that occur at the onset of involution of rat mammary glands. Methods:Mammary tissue was collected post-mortem from lactating Sprague-Dawley rats at 0, 1, 3, and 6 h (n=6 per time point) following acute physical distension of an inguinal gland with isosmotic sucrose solution (0.8 ml; equivalent to ~6 h worth of milk accumulation) via the teat canal followed by sealing with adhesive (infused). The remaining teats on each rat were either left unsealed for pups to suckle (control), or were sealed to induce milk accumulation and mammary engorgement (engorged). Results:There was a low number of positive in situ-end labeled (ISEL) nuclei in suckled control glands indicating they had a low number of cells with fragmented DNA or were apoptotic. However, there was a greater number of ISEL nuclei in sucrose-infused and milk-engorged teat-sealed glands by 1 and 6 h, respectively, such that these changes were accelerated by sucrose infusion, compared with milk accumulation alone. The timing of the decline in abundance of β1-integrin (cell-extracellular matrix protein) and occludin (tight junction protein), and increase in abundance of the activated apoptotic marker signal transducer and activator of transcription factor-3 (pSTAT3) protein were also accelerated by sucrose infusion. Conclusion:Physical distension by sucrose infusion accelerated the onset of the first stage of mammary apoptosis and involution, supporting a role for mechanotransduction during these processes.

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“…On the other hand, massive activation of the plasmin activity (X150%) is associated with extensive degradation of casein, an inflammatory response (increase in leukocytes and NAGase activity), reduction in lactose concentration and disruption of tight junctions. As a result, fluid, fat and protein secretion are negatively affected, as seen in the response to treatment with CNH of goats (Shamay et al, 2002) and cows (Shamay et al, 2003).…”

Section: Int J Dairy Sci 10 (3): 95-106 2015mentioning

confidence: 99%

PA-PG-PL System in Dairy Animals and its Significance: A Review

Haque¹,

Singh²,

Hossain³

2015

International J. of Dairy Science

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Animal husbandry plays an important role in strengthening the rural economy. Heat is a major constraint on animal productivity in the tropical belt and arid areas. Heat stress in dairy cows as all temperature-related forces encourage changes or adjustments which may occur from the cellular to the total animal level to help the cows stay away from physiological disorders and then to better adapt to an adverse thermal environment. Milk production is impaired as a result of the drastic changes in biological functions under heat stress. Activation of the hypothalamus-pituitary-adrenocortical axis by external stress liberates cortisol into blood plasma, which in turn induces the liberation of Plasminogen Activator (PA) from the mammary epithelial cells, where it activates the Plasminogen-Plasmin (PG-PL) system. Thus, this PA-PG-PL system is a milk-borne factor which down regulates the milk secretion during the summer stress. This negative feedback system specifically forms β-casein (CN) fragment (f) (1-28) from β-CN, which acts as the negative control signal of mammary gland. Based on these findings, casein hydrolyzate preparation is developed to reduce suffering from mammary gland engorgement associated with abrupt cessation of milking and to treat common clinical and subclinical infections of udder in dairy cows.

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Casein-derived phosphopeptides disrupt tight junction integrity, and precipitously dry up milk secretion in goats

Cited by 72 publications

References 19 publications

Lipopolysaccharide challenge of the mammary gland in cows induces nitrosative stress that impairs milk oxidative stability

Lipopolysaccharide challenge of the mammary gland in cows induces nitrosative stress that impairs milk oxidative stability

Induced Physical Distension of Rat Mammary Glands Accelerates the Onset of Apoptosis and Involution

PA-PG-PL System in Dairy Animals and its Significance: A Review

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