PMID- 22253885
OWN - NLM
STAT- MEDLINE
DCOM- 20120529
LR  - 20240216
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 7
IP  - 1
DP  - 2012
TI  - HIV-1 promotes renal tubular epithelial cell protein synthesis: role of mTOR 
      pathway.
PG  - e30071
LID - 10.1371/journal.pone.0030071 [doi]
LID - e30071
AB  - Tubular cell HIV-infection has been reported to manifest in the form of cellular 
      hypertrophy and apoptosis. In the present study, we evaluated the role of 
      mammalian target of rapamycin (mTOR) pathway in the HIV induction of tubular cell 
      protein synthesis. Mouse proximal tubular epithelial cells (MPTECs) were 
      transduced with either gag/pol-deleted NL4-3 (HIV/MPTEC) or empty vector 
      (Vector/MPTEC). HIV/MPTEC showed enhanced DNA synthesis when compared with 
      Vector/MPTECs by BRDU labeling studies. HIV/MPTECs also showed enhanced 
      production of beta-laminin and fibronection in addition to increased protein content 
      per cell. In in vivo studies, renal cortical sections from HIV transgenic mice 
      and HIVAN patients showed enhanced tubular cell phosphorylation of mTOR. Analysis 
      of mTOR revealed increased expression of phospho (p)-mTOR in HIV/MPTECs when 
      compared to vector/MPTECs. Further downstream analysis of mTOR pathway revealed 
      enhanced phosphorylation of p70S6 kinase and associated diminished 
      phosphorylation of eEF2 (eukaryotic translation elongation factor 2) in 
      HIV/MPTECs; moreover, HIV/MPTECs displayed enhanced phosphorylation of eIF4B 
      (eukaryotic translation initiation factor 4B) and 4EBP-1 (eukaryotic 4E binding 
      protein). To confirm our hypothesis, we evaluated the effect of rapamycin on 
      HIV-induced tubular cell downstream signaling. Rapamycin not only attenuated 
      phosphorylation of p70S6 kinase and associated down stream signaling in 
      HIV/MPTECs but also inhibited HIV-1 induced tubular cell protein synthesis. These 
      findings suggest that mTOR pathway is activated in HIV-induced enhanced tubular 
      cell protein synthesis and contributes to tubular cell hypertrophy.
FAU - Rehman, Shabina
AU  - Rehman S
AD  - Department of Medicine, North Shore LIJ Health System, New York, New York, United 
      States of America.
FAU - Husain, Mohammad
AU  - Husain M
FAU - Yadav, Anju
AU  - Yadav A
FAU - Kasinath, Balakuntalam S
AU  - Kasinath BS
FAU - Malhotra, Ashwani
AU  - Malhotra A
FAU - Singhal, Pravin C
AU  - Singhal PC
LA  - eng
GR  - R01 DK084910/DK/NIDDK NIH HHS/United States
GR  - R01DK084910/DK/NIDDK NIH HHS/United States
GR  - R01 DK077295/DK/NIDDK NIH HHS/United States
GR  - R01DK077295/DK/NIDDK NIH HHS/United States
GR  - R01 DK083931/DK/NIDDK NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20120109
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (Fibronectins)
RN  - 0 (Laminin)
RN  - 0 (Peptide Elongation Factor 2)
RN  - 0 (Pol1 Transcription Initiation Complex Proteins)
RN  - 0 (transcription factor UBF)
RN  - 9007-49-2 (DNA)
RN  - EC 2.7.11.1 (Ribosomal Protein S6 Kinases, 70-kDa)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - W36ZG6FT64 (Sirolimus)
SB  - IM
MH  - AIDS-Associated Nephropathy/metabolism/virology
MH  - Animals
MH  - DNA/biosynthesis
MH  - Enzyme Activation
MH  - Epithelial Cells/*metabolism/pathology/*virology
MH  - Fibronectins/biosynthesis
MH  - HIV-1/drug effects/*physiology
MH  - Humans
MH  - Intracellular Space/drug effects/metabolism
MH  - Kidney Tubules/*pathology
MH  - Laminin/biosynthesis
MH  - Mice
MH  - Models, Biological
MH  - Peptide Elongation Factor 2/metabolism
MH  - Phosphorylation/drug effects
MH  - Pol1 Transcription Initiation Complex Proteins/metabolism
MH  - *Protein Biosynthesis/drug effects
MH  - Ribosomal Protein S6 Kinases, 70-kDa/metabolism
MH  - *Signal Transduction/drug effects
MH  - Sirolimus/pharmacology
MH  - TOR Serine-Threonine Kinases/*metabolism
PMC - PMC3253808
COIS- Competing Interests: The authors have declared that no competing interests exist.
EDAT- 2012/01/19 06:00
MHDA- 2012/05/30 06:00
PMCR- 2012/01/09
CRDT- 2012/01/19 06:00
PHST- 2011/06/27 00:00 [received]
PHST- 2011/12/13 00:00 [accepted]
PHST- 2012/01/19 06:00 [entrez]
PHST- 2012/01/19 06:00 [pubmed]
PHST- 2012/05/30 06:00 [medline]
PHST- 2012/01/09 00:00 [pmc-release]
AID - PONE-D-11-11912 [pii]
AID - 10.1371/journal.pone.0030071 [doi]
PST - ppublish
SO  - PLoS One. 2012;7(1):e30071. doi: 10.1371/journal.pone.0030071. Epub 2012 Jan 9.