PMID- 12556365
OWN - NLM
STAT- MEDLINE
DCOM- 20030312
LR  - 20161124
IS  - 1931-857X (Print)
IS  - 1522-1466 (Linking)
VI  - 284
IP  - 3
DP  - 2003 Mar
TI  - Heme: a novel inducer of MCP-1 through HO-dependent and HO-independent 
      mechanisms.
PG  - F546-54
AB  - This study examined the effect of hemin on the expression of heme oxygenase-1 
      (HO-1) and monocyte chemoattractant protein-1 (MCP-1) in immortalized rat 
      proximal tubular epithelial cells (IRPTCs). Hemin elicited a dose- and 
      time-dependent induction of HO-1 and MCP-1 mRNA. HO activity contributed to MCP-1 
      mRNA expression at early time points (4-6 h) because inhibition of HO activity by 
      zinc protoporphyrin (ZnPP) prevented hemin-induced expression of MCP-1 mRNA. 
      Catalytically active intracellular iron was markedly increased in hemin-treated 
      IRPTCs and contributed to the induction of HO-1 and MCP-1 mRNA because an iron 
      chelator blocked hemin-induced upregulation of both genes, whereas a 
      cell-permeant form of iron directly induced these genes. N-acetylcysteine 
      completely blocked hemin-induced expression of HO-1 and MCP-1 mRNA, thereby 
      providing added evidence for redox regulation of expression of these genes. The 
      redox-sensitive transcription factor NF-kappaB was recruited in hemin-induced 
      upregulation of MCP-1 because two different compounds that abrogate the 
      activation of NF-kappaB (TPCK and BAY 11-7082) completely blocked hemin-induced 
      upregulation of MCP-1 mRNA. In contrast to this HO-mediated induction of MCP-1 
      through redox-sensitive, iron-dependent, and NF-kappaB-involved pathways observed 
      after 4-6 h, hemin also elicited a delayed induction of MCP-1 at 18 h through 
      HO-independent pathways. We conclude that hemin is a potent inducer of MCP-1 in 
      IRPTCs: HO-dependent, heme-degrading pathways lead to an early, robust, and 
      self-remitting induction of MCP-1, whereas HO-independent mechanisms lead to a 
      delayed expression of MCP-1.
FAU - Kanakiriya, Sharan K R
AU  - Kanakiriya SK
AD  - Division of Nephrology, Mayo Clinic/Foundation, Rochester, Minnesota 55905, USA.
FAU - Croatt, Anthony J
AU  - Croatt AJ
FAU - Haggard, Jill J
AU  - Haggard JJ
FAU - Ingelfinger, Julie R
AU  - Ingelfinger JR
FAU - Tang, Shiow-Shih
AU  - Tang SS
FAU - Alam, Jawed
AU  - Alam J
FAU - Nath, Karl A
AU  - Nath KA
LA  - eng
GR  - DK-43135/DK/NIDDK NIH HHS/United States
GR  - DK-50835/DK/NIDDK NIH HHS/United States
GR  - DK-58950/DK/NIDDK NIH HHS/United States
GR  - HL-48455/HL/NHLBI NIH HHS/United States
GR  - HL-55552/HL/NHLBI NIH HHS/United States
GR  - R01-DK-47060/DK/NIDDK NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Am J Physiol Renal Physiol
JT  - American journal of physiology. Renal physiology
JID - 100901990
RN  - 0 (Chemokine CCL2)
RN  - 0 (RNA, Messenger)
RN  - 743LRP9S7N (Hemin)
RN  - EC 1.14.14.18 (Heme Oxygenase (Decyclizing))
RN  - EC 1.14.14.18 (Heme Oxygenase-1)
SB  - IM
MH  - Animals
MH  - Blotting, Northern
MH  - Cell Line
MH  - Chemokine CCL2/genetics/*metabolism
MH  - Dose-Response Relationship, Drug
MH  - Epithelial Cells/cytology/*drug effects
MH  - Gene Expression Regulation/drug effects
MH  - Heme Oxygenase (Decyclizing)/genetics/*metabolism
MH  - Heme Oxygenase-1
MH  - Hemin/*pharmacology
MH  - Kidney Tubules, Proximal/cytology/*drug effects
MH  - RNA, Messenger/metabolism
MH  - Rats
MH  - Up-Regulation/drug effects
EDAT- 2003/01/31 04:00
MHDA- 2003/03/13 04:00
CRDT- 2003/01/31 04:00
PHST- 2003/01/31 04:00 [pubmed]
PHST- 2003/03/13 04:00 [medline]
PHST- 2003/01/31 04:00 [entrez]
AID - 284/3/F546 [pii]
AID - 10.1152/ajprenal.00298.2002 [doi]
PST - ppublish
SO  - Am J Physiol Renal Physiol. 2003 Mar;284(3):F546-54. doi: 
      10.1152/ajprenal.00298.2002.