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Phosphorylation of nuclear factor erythroid 2-like 2 (NFE2L2) in mammary tissue of Holstein cows during the periparturient period is associated with mRNA abundance of antioxidant gene networks

文献类型: 外文期刊

作者: Han, L. Q. 1 ; Zhou, Z. 4 ; Ma, Y. 2 ; Batistel, F. 2 ; Osorio, J. S. 6 ; Loor, J. J. 2 ;

作者机构: 1.Henan Agr Univ, Coll Anim Sci & Vet Med, Zhengzhou 450002, Henan, Peoples R China

2.Univ Illinois, Mammalian NutriPhysioGen, Dept Anim Sci, Urbana, IL 61801 USA

3.Univ Illinois, Div Nutr Sci, Urbana, IL 61801 USA

4.Clemson Univ, Dept Anim & Vet Sci, 146 Poole Agr Ctr, Clemson, SC 29634 USA

5.Inner Mongolia Acad Agr & Anim Husb Sci, Inst Anim Nutr & Feed, Hohhot 010031, Peoples R China

6.South Dakota State Univ, Dairy & Food Sci Dept, 1111 Coll Ave,113H Alfred Dairy Sci Hall, Brookings, SD 57007 USA

关键词: oxidative stress; lactation; reactive oxygen metabolites

期刊名称:JOURNAL OF DAIRY SCIENCE ( 影响因子:4.034; 五年影响因子:4.354 )

ISSN: 0022-0302

年卷期: 2018 年 101 卷 7 期

页码:

收录情况: SCI

摘要: Changes in the production of reactive oxygen species in the mammary gland of dairy cows during the periparturient period could lead to oxidative stress and potentially impair mammary function. Phosphorylation of the transcription factor nuclear factor erythroid 2-like 2 (NFE2L2), also known as nuclear factor-E2-related factor 2, controls mRNA abundance of genes encoding antioxidant proteins and enzymes. The hypothesis was that NFE2L2 phosphorylation status and target gene mRNA abundance in the mammary gland of dairy cows is altered around parturition. Total NFE2L2 protein, phosphorylated protein (p-NFE2L2), and ratio of p-NFE2L2 to NFE2L2 along with mRNA abundance of 24 genes related to the NFE2L2 signaling pathway, apoptosis, and cell proliferation were measured in mammary tissue samples from Holstein cows at -30, 1, 15, and 30 d relative to parturition. Although total NFE2L2 protein abundance did not differ, p-NFE2L2 and p-NFE2L2-to-NFE2L2 ratio were greater after parturition. The upregulation of DNA damage inducible transcript 3 (DDIT3) postpartum indicated a localized oxidative stress state. Among genes evaluated, thioredoxin (TXN), glutathione peroxidase 1 (GPX1), and glutathione S-transferase mu 1 (GSTM1) had the highest (37.1, 15.1, and 4.8% of total mRNA measured, respectively) abundance. The mRNA abundance of various target genes with detoxifying enzymatic functions and free radical scavenging activities [glutamate-cysteine ligase catalytic subunit (GCLC); glutathione reductase (GSR); ferrochelatase (FECH); TXN; thioredoxin reductase 1 (TXNRD1); and NAD(P)H quinone dehydrogenase 1 (NQO1)] were consistently upregulated (linear effect of time) as parturition approached and lactation began. Among the transcription regulators, NFE2L2 had the highest mRNA abundance (7.3% of total mRNA measured). Abundance of NFE2L2 and other transcription factors [nuclear factor kappa B subunit 1 (NFKB1), retinoid X receptor alpha (RXRA), and mitogen-activated protein kinase 14 (MAPK14)] were upregulated (linear effect of time) from -30 d to 30 d relative to parturition. Overall, NFE2L2 phosphorylation and downstream signaling leading to postpartal upregulation of genes associated with oxidative stress and inflammation in the mammary gland seem to be key components of normal cellular function to maintain proper redox homeostasis. However, if the longitudinal increases in mRNA and protein abundance of these antioxidant mechanisms are a reflection of cellular oxidative stress, then the likelihood of protein and DNA damage would be greater and might be one factor compromising cell viability and potentially lactation persistency. The actual cues coordinating these molecular responses remain to be determined.

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