PMID- 27495870
OWN - NLM
STAT- MEDLINE
DCOM- 20170522
LR  - 20181202
IS  - 1090-2104 (Electronic)
IS  - 0006-291X (Print)
IS  - 0006-291X (Linking)
VI  - 478
IP  - 2
DP  - 2016 Sep 16
TI  - Sortilin facilitates VLDL-B100 secretion by insulin sensitive McArdle 
      RH7777 cells.
PG  - 546-52
LID - S0006-291X(16)31218-9 [pii]
LID - 10.1016/j.bbrc.2016.07.096 [doi]
AB  - Studies examining the relationship between cellular sortilin and VLDL-B100 
      secretion demonstrate inconsistent results. Current studies explore the 
      possibility that discrepancies may be related to insulin sensitivity. McArdle 
      RH7777 cells (McA cells) cultured under serum enriched conditions lose 
      sensitivity to insulin. Following incubation in serum-free DMEM containing 1% 
      BSA, McA cells become insulin responsive and demonstrate reduced apo B secretion. 
      Current studies indicate that insulin sensitive McA cells express lower cellular 
      sortilin that corresponds with reduction in VLDL-B100 secretion without changes 
      in mRNA of either sortilin or apo B. When sortilin expression is further reduced 
      by siRNA knockdown (KD), there are additional decreases in VLDL-B100 secretion. A 
      crystal structure of human sortilin (hsortilin) identifies two binding sites on 
      the luminal domain for the N- and C-termini of neurotensin (NT). A small organic 
      compound (cpd984) was identified that has strong theoretical binding to the 
      N-terminal site. Both cpd984 and NT bind hsortilin by surface plasmon resonance. 
      In incubations with insulin sensitive McA cells, cpd984 was shown to enhance 
      VLDL-B100 secretion at each level of sortilin KD suggesting cpd984 acted through 
      sortilin in mediating its effect. Current results support a role for sortilin to 
      facilitate VLDL-B100 secretion which is limited to insulin sensitive McA cells. 
      Inconsistent reports of the relationship between VLDL-B100 secretion and sortilin 
      in previous studies may relate to differing functions of sortilin in VLDL-B100 
      secretion depending upon insulin sensitivity.
CI  - Copyright (c) 2016 Elsevier Inc. All rights reserved.
FAU - Sparks, Robert P
AU  - Sparks RP
AD  - School of Molecular and Cellular Biology, Department of Biochemistry, University 
      of Illinois Urbana-Champaign, Urbana, IL 61801, USA.
FAU - Guida, Wayne C
AU  - Guida WC
AD  - Department of Chemistry, University of South Florida, Tampa, FL 33520, USA.
FAU - Sowden, Mark P
AU  - Sowden MP
AD  - Cardiovascular Research Institute, University of Rochester Medical Center, 
      Rochester, NY 14642, USA.
FAU - Jenkins, Jermaine L
AU  - Jenkins JL
AD  - Department of Biochemistry and Biophysics, University of Rochester Medical 
      Center, Rochester, NY 14642, USA.
FAU - Starr, Matthew L
AU  - Starr ML
AD  - School of Molecular and Cellular Biology, Department of Biochemistry, University 
      of Illinois Urbana-Champaign, Urbana, IL 61801, USA.
FAU - Fratti, Rutilio A
AU  - Fratti RA
AD  - School of Molecular and Cellular Biology, Department of Biochemistry, University 
      of Illinois Urbana-Champaign, Urbana, IL 61801, USA.
FAU - Sparks, Charles E
AU  - Sparks CE
AD  - Department of Pathology and Laboratory Medicine, University of Rochester Medical 
      Center, Rochester, NY 14642, USA.
FAU - Sparks, Janet D
AU  - Sparks JD
AD  - Department of Pathology and Laboratory Medicine, University of Rochester Medical 
      Center, Rochester, NY 14642, USA. Electronic address: 
      Janet_Sparks@urmc.rochester.edu.
LA  - eng
GR  - R01 DK100163/DK/NIDDK NIH HHS/United States
GR  - R01 GM101132/GM/NIGMS NIH HHS/United States
GR  - T32 GM070421/GM/NIGMS NIH HHS/United States
PT  - Journal Article
DEP - 20160802
PL  - United States
TA  - Biochem Biophys Res Commun
JT  - Biochemical and biophysical research communications
JID - 0372516
RN  - 0 (Adaptor Proteins, Vesicular Transport)
RN  - 0 (Apolipoprotein B-100)
RN  - 0 (Insulin)
RN  - 0 (Lipoproteins, VLDL)
RN  - Z020Y8WIJ4 (sortilin)
SB  - IM
MH  - Adaptor Proteins, Vesicular Transport/chemistry/genetics/*metabolism
MH  - Animals
MH  - Apolipoprotein B-100/*metabolism
MH  - Binding Sites
MH  - Cell Line
MH  - Gene Knockdown Techniques
MH  - Humans
MH  - Insulin/*metabolism
MH  - *Insulin Resistance
MH  - Lipoproteins, VLDL/*metabolism
MH  - Molecular Docking Simulation
MH  - Rats, Sprague-Dawley
PMC - PMC5002383
MID - NIHMS808925
OTO - NOTNLM
OT  - Apo B
OT  - Liver
OT  - Neurotensin
OT  - Sortilin
OT  - Surface plasmon resonance
OT  - VLDL-B100
EDAT- 2016/08/09 06:00
MHDA- 2017/05/23 06:00
PMCR- 2017/09/16
CRDT- 2016/08/07 06:00
PHST- 2016/07/17 00:00 [received]
PHST- 2016/07/21 00:00 [accepted]
PHST- 2016/08/07 06:00 [entrez]
PHST- 2016/08/09 06:00 [pubmed]
PHST- 2017/05/23 06:00 [medline]
PHST- 2017/09/16 00:00 [pmc-release]
AID - S0006-291X(16)31218-9 [pii]
AID - 10.1016/j.bbrc.2016.07.096 [doi]
PST - ppublish
SO  - Biochem Biophys Res Commun. 2016 Sep 16;478(2):546-52. doi: 
      10.1016/j.bbrc.2016.07.096. Epub 2016 Aug 2.