Abstract
Opioid growth factor (OGF) is an endogenous opioid peptide ([Met 5]enkephalin) that interacts with the OGF receptor (OGFr) and serves as a tonically active negative growth factor in cell proliferation of normal cells. To clarify the mechanism by which OGF inhibits cell replication in normal cells, we investigated the effect of the OGF-OGFr axis on cell cycle activity in human umbilical vein endothelial cells (HUVECs) and human epidermal keratinocytes (NHEKs). OGF markedly depressed cell proliferation of both cell lines by up to 40% of sterile water controls. Peptide treatment induced cyclin-dependent kinase inhibitor (CKI) p16 INK4a protein expression and p21 WAF1/CIP1 protein expression in HUVECs and NHEKs, but had no effect on p15, p18, p19, or p27 protein expression in either cell type. Inhibition of either p16 INK4a or p21 WAF1/CIP1 activation by specific siRNAs blocked OGF inhibitory action. Human dermal fibroblasts and mesenchymal stem cells also showed a similar dependence of OGF action on p16 INK4a and p21 WAF1/CIP1. Collectively, these results indicate that both p16 INK4a and p21 WAF1/CIP1 are required for the OGF-OGFr axis to inhibit cell proliferation in normal cells.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 319-327 |
| Number of pages | 9 |
| Journal | Molecular biology of the cell |
| Volume | 20 |
| Issue number | 1 |
| DOIs | |
| State | Published - Jan 1 2009 |
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All Science Journal Classification (ASJC) codes
- Molecular Biology
- Cell Biology
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The OGF-OGFr axis utilizes the p16 INK4a and p21 WAF1/CIP1 pathways to restrict normal cell proliferation. / Cheng, Fan; McLaughlin, Patricia J.; Verderame, Michael F.; Zagon, Ian S.
In: Molecular biology of the cell, Vol. 20, No. 1, 01.01.2009, p. 319-327.Research output: Contribution to journal › Article
TY - JOUR
T1 - The OGF-OGFr axis utilizes the p16 INK4a and p21 WAF1/CIP1 pathways to restrict normal cell proliferation
AU - Cheng, Fan
AU - McLaughlin, Patricia J.
AU - Verderame, Michael F.
AU - Zagon, Ian S.
PY - 2009/1/1
Y1 - 2009/1/1
N2 - Opioid growth factor (OGF) is an endogenous opioid peptide ([Met 5]enkephalin) that interacts with the OGF receptor (OGFr) and serves as a tonically active negative growth factor in cell proliferation of normal cells. To clarify the mechanism by which OGF inhibits cell replication in normal cells, we investigated the effect of the OGF-OGFr axis on cell cycle activity in human umbilical vein endothelial cells (HUVECs) and human epidermal keratinocytes (NHEKs). OGF markedly depressed cell proliferation of both cell lines by up to 40% of sterile water controls. Peptide treatment induced cyclin-dependent kinase inhibitor (CKI) p16 INK4a protein expression and p21 WAF1/CIP1 protein expression in HUVECs and NHEKs, but had no effect on p15, p18, p19, or p27 protein expression in either cell type. Inhibition of either p16 INK4a or p21 WAF1/CIP1 activation by specific siRNAs blocked OGF inhibitory action. Human dermal fibroblasts and mesenchymal stem cells also showed a similar dependence of OGF action on p16 INK4a and p21 WAF1/CIP1. Collectively, these results indicate that both p16 INK4a and p21 WAF1/CIP1 are required for the OGF-OGFr axis to inhibit cell proliferation in normal cells.
AB - Opioid growth factor (OGF) is an endogenous opioid peptide ([Met 5]enkephalin) that interacts with the OGF receptor (OGFr) and serves as a tonically active negative growth factor in cell proliferation of normal cells. To clarify the mechanism by which OGF inhibits cell replication in normal cells, we investigated the effect of the OGF-OGFr axis on cell cycle activity in human umbilical vein endothelial cells (HUVECs) and human epidermal keratinocytes (NHEKs). OGF markedly depressed cell proliferation of both cell lines by up to 40% of sterile water controls. Peptide treatment induced cyclin-dependent kinase inhibitor (CKI) p16 INK4a protein expression and p21 WAF1/CIP1 protein expression in HUVECs and NHEKs, but had no effect on p15, p18, p19, or p27 protein expression in either cell type. Inhibition of either p16 INK4a or p21 WAF1/CIP1 activation by specific siRNAs blocked OGF inhibitory action. Human dermal fibroblasts and mesenchymal stem cells also showed a similar dependence of OGF action on p16 INK4a and p21 WAF1/CIP1. Collectively, these results indicate that both p16 INK4a and p21 WAF1/CIP1 are required for the OGF-OGFr axis to inhibit cell proliferation in normal cells.
UR - http://www.scopus.com/inward/record.url?scp=63049083971&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=63049083971&partnerID=8YFLogxK
U2 - 10.1091/mbc.E08-07-0681
DO - 10.1091/mbc.E08-07-0681
M3 - Article
C2 - 18923142
AN - SCOPUS:63049083971
VL - 20
SP - 319
EP - 327
JO - Molecular Biology of the Cell
JF - Molecular Biology of the Cell
SN - 1059-1524
IS - 1
ER -