PMID- 31942894
OWN - NLM
STAT- MEDLINE
DCOM- 20201008
LR  - 20201008
IS  - 2042-650X (Electronic)
IS  - 2042-6496 (Linking)
VI  - 11
IP  - 1
DP  - 2020 Jan 29
TI  - Supply of methionine and arginine alters phosphorylation of mechanistic target of 
      rapamycin (mTOR), circadian clock proteins, and alpha-s1-casein abundance in bovine 
      mammary epithelial cells.
PG  - 883-894
LID - 10.1039/c9fo02379h [doi]
AB  - Methionine (Met) and arginine (Arg) regulate casein protein abundance through 
      alterations in activity of the mechanistic target of rapamycin complex 1 (mTORC1) 
      signaling pathway. A potential role for the circadian clock network on the 
      regulation of protein synthesis, partly via activity of mTORC1, has been 
      highlighted in non-ruminants. The main objective of the study was to determine in 
      ruminant mammary cells alterations in mRNA, protein abundance and phosphorylation 
      status of mTORC1-related upstream targets, circadian clock proteins, and protein 
      kinase AMP-activated catalytic subunit alpha (AMPK) in relation to alpha-s1-casein 
      protein (CSN1S1) abundance in response to greater supply of Met and Arg alone or 
      in combination. Primary bovine mammary epithelial cells (BMEC) were incubated for 
      12 h in a 2 x 2 arrangement of treatments with control media (ideal profile of 
      amino acids, IPAA), or media supplemented with increased Met (incMet), Arg 
      (incArg), or both (incMet + incArg). Data were analyzed testing the main effects 
      of Met and Arg and their interaction. Among 7 amino acid (AA) transporters known 
      to be mTORC1 targets, increasing supply of Arg downregulated SLC1A5, SLC3A2, 
      SLC7A1, and SLC7A5, while increasing supply of Met upregulated SLC7A1. mRNA 
      abundance of the cytosolic Arg sensor (CASTOR1) was lower when supply of Arg and 
      Met alone increased. p-TSC2 (TSC complex subunit 2) was greater when the Arg 
      supply was increased, while the phosphoralation ratio of p-AKT (AKT 
      serine/threonine kinase 1):total (t) AKT and p-AMPK:tAMPK were lower. In spite of 
      this, the ratio of p-mTOR:tmTOR nearly doubled with incArg but such response did 
      not prevent a decrease in CSN1S1 abundance. The abundance of period circadian 
      regulator 1 (PER1) protein nearly doubled with all treatments, but only incMet + 
      incArg led to greater clock circadian regulator (CLOCK) protein abundance. 
      Overall, data suggest that a greater supply of Met and Arg could influence CSN1S1 
      synthesis of BMEC through changes in the mTORC1, circadian clock, and AMPK 
      pathways. Identifying mechanistic relationships between intracellular energy, 
      total AA supply, and these pathways in the context of milk protein synthesis in 
      ruminants merits further research.
FAU - Hu, Liangyu
AU  - Hu L
AD  - College of Animal Science and Technology, Yangzhou University, Yangzhou, 225009, 
      P.R. China. mengzhiwang@126.com.
FAU - Chen, Yifei
AU  - Chen Y
FAU - Cortes, Ismael M
AU  - Cortes IM
FAU - Coleman, Danielle N
AU  - Coleman DN
FAU - Dai, Hongyu
AU  - Dai H
FAU - Liang, Yusheng
AU  - Liang Y
FAU - Parys, Claudia
AU  - Parys C
FAU - Fernandez, Carlos
AU  - Fernandez C
FAU - Wang, Mengzhi
AU  - Wang M
FAU - Loor, Juan J
AU  - Loor JJ
LA  - eng
PT  - Journal Article
PL  - England
TA  - Food Funct
JT  - Food & function
JID - 101549033
RN  - 0 (Caseins)
RN  - 0 (Circadian Rhythm Signaling Peptides and Proteins)
RN  - 0 (Milk Proteins)
RN  - 94ZLA3W45F (Arginine)
RN  - AE28F7PNPL (Methionine)
SB  - IM
MH  - Animals
MH  - Arginine/*metabolism
MH  - Caseins/metabolism
MH  - Cattle
MH  - Circadian Rhythm Signaling Peptides and Proteins/metabolism
MH  - Epithelial Cells/*metabolism
MH  - Female
MH  - Mammary Glands, Animal/*cytology
MH  - Methionine/*metabolism
MH  - Milk Proteins/metabolism
MH  - Phosphorylation
EDAT- 2020/01/17 06:00
MHDA- 2020/10/09 06:00
CRDT- 2020/01/17 06:00
PHST- 2020/01/17 06:00 [pubmed]
PHST- 2020/10/09 06:00 [medline]
PHST- 2020/01/17 06:00 [entrez]
AID - 10.1039/c9fo02379h [doi]
PST - ppublish
SO  - Food Funct. 2020 Jan 29;11(1):883-894. doi: 10.1039/c9fo02379h.