Detection of a single nucleotide polymorphism in the human α-lactalbumin gene: implications for human milk proteins

Chowanadisai, Winyoo; Kelleher, Shannon L.; Nemeth, Jennifer F.; Yachetti, Stephen; Kuhlman, Charles F.; Jackson, Joan G.; Davis, Anne M.; Lien, Eric L.; Lönnerdal, Bo

doi:10.1016/j.jnutbio.2004.12.010

Cited by 25 publications

(12 citation statements)

References 42 publications

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“…The full-length wild-type form of ZnT2 protein tagged with a C-terminal tandem hemagglutinin (HA; T 288 ) was generated as previously described 75 . The ZnT2 variant substituting a threonine for a serine at amino acid 288 (S 288 ) was generated as previously described 1 .…”

Section: Methodsmentioning

confidence: 99%

A genetic variant in SLC30A2 causes breast dysfunction during lactation by inducing ER stress, oxidative stress and epithelial barrier defects

Lee

Zhou

Gill

et al. 2018

Sci Rep

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SLC30A2 encodes a zinc (Zn) transporter (ZnT2) that imports Zn into vesicles in highly-specialized secretory cells. Numerous mutations and non-synonymous variants in ZnT2 have been reported in humans and in breastfeeding women; ZnT2 variants are associated with abnormally low milk Zn levels and can lead to severe infantile Zn deficiency. However, ZnT2-null mice have profound defects in mammary epithelial cell (MEC) polarity and vesicle secretion, indicating that normal ZnT2 function is critical for MEC function. Here we report that women who harbor a common ZnT2 variant (T288S) present with elevated levels of several oxidative and endoplasmic reticulum (ER) stress markers in their breast milk. Functional studies in vitro suggest that substitution of threonine for serine at amino acid 288 leads to hyperphosphorylation retaining ZnT2 in the ER and lysosomes, increasing ER and lysosomal Zn accumulation, ER stress, the generation of reactive oxygen species, and STAT3 activation. These changes were associated with decreased abundance of zona occludens-1 and increased tight junction permeability. This study confirms that ZnT2 is important for normal breast function in women during lactation, and suggests that women who harbor defective variants in ZnT2 may be at-risk for poor lactation performance.

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Section: Methodsmentioning

confidence: 99%

A genetic variant in SLC30A2 causes breast dysfunction during lactation by inducing ER stress, oxidative stress and epithelial barrier defects

Lee

Zhou

Gill

et al. 2018

Sci Rep

Self Cite

View full text Add to dashboard Cite

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“…2) (Godovac Zimmerman, Shaw, Conti, & McKenzie,1987). Bovine a-La occurs as two, or possibly three, genetic variants (Bell, Hopper, & McKenzie, 1981a) and human a-La has two genetic variants, one of which has been identified only recently (Chowanadisaia et al, 2005). The primary structures of equine, bovine and human a-La differ only by a few single amino acid replacements, and the proteins have similar properties (Table 6).…”

Section: B-lactoglobulinmentioning

confidence: 99%

Equine milk proteins: Chemistry, structure and nutritional significance

Uniacke‐Lowe

Huppertz

Fox

2010

International Dairy Journal

178

170

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“…Variation in composition of milk proteins over the course of lactation is due primarily to programmed changes in protein expression (9-11). Variability in milk protein concentrations among individuals has been attributed to genetic variation (12, 13), maternal adiposity (14), and other factors. Adipose tissue is the primary source of adiponectin.…”

Section: Adiponectin In Milkmentioning

confidence: 99%

Characteristics and Potential Functions of Human Milk Adiponectin

Newburg

Woo

Morrow

2010

The Journal of Pediatrics

103

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Adiponectin is a protein hormone produced by adipose tissue whose circulating levels are inversely related to adiposity and inflammation. Adiponectin circulates as oligomers, from the low molecular weight trimer to the high molecular weight octodecamer (18mer) Each oligomer has distinct biological activities, which include enhancement of insulin sensitivity and metabolic control, and suppression of inflammation. Adiponectin occurs in human milk at higher concentrations than leptin. The adiponectin in human milk is almost entirely of the high molecular weight form, the form with the highest activity in controlling many types of metabolic processes. Human adiponectin fed to infant mice is transported across the intestinal mucosa into the serum. An inverse relationship between adiponectin levels in milk and adiposity (weight-for-height) of the breastfed infant was observed, and could be due to modulation of infant metabolism by milk adiponectin, and may be related to the observed protection against obesity by breastfeeding. Human milk may be a medium whereby the hormonal milieu (in response to internal factors and the environment) of the mother can be used to communicate with the breastfed infant to modify infant metabolic processes. Transmission of information from mother to infant through milk may allow adaptation to fluctuating environmental conditions. Keywords infant development; body weight; BMI; adiposity AdiponectinObesity in children has reached epidemic proportions, with obesity-related disorders that had typically been diseases of adults now occurring in children. Several reports describe an association between feeding human milk and reduced obesity later in life. Likewise, inflammatory bowel diseases are an increasingly important problem in pediatrics, and there is evidence of protection by human milk. The mechanisms by which human milk could provide , and all potential conflicts of interest have been disclosed to the NIH and are being managed by Massachusetts General Hospital and Cincinnati Children's Hospital, respectively. Jessica Woo, Ph.D. has no affiliation with entitles having financial interests in the subject discussed in this article. Mead Johnson Nutrition sponsored a symposium and provided an honorarium to participants. This review of the symposium presentation was written exclusively by the authors, who have no financial interests in production or sales of infant formula.Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. Adiponectin, a protein produced in adipose tissue, is a potent metabolic mediator that controls processes associated with obes...

show abstract

Detection of a single nucleotide polymorphism in the human α-lactalbumin gene: implications for human milk proteins

Cited by 25 publications

References 42 publications

A genetic variant in SLC30A2 causes breast dysfunction during lactation by inducing ER stress, oxidative stress and epithelial barrier defects

A genetic variant in SLC30A2 causes breast dysfunction during lactation by inducing ER stress, oxidative stress and epithelial barrier defects

Equine milk proteins: Chemistry, structure and nutritional significance

Characteristics and Potential Functions of Human Milk Adiponectin

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