![[Feedback]](/icons/banner/feedbackACT.gif){kind=icon}
![[For Subscribers]](/icons/banner/subscriberACT.gif){kind=icon}
![[Archive]](/icons/banner/archiveACT.gif){kind=icon}
![[Search]](/icons/banner/searchACT.gif){kind=icon}
![[Contents]](/icons/banner/tocACT.gif){kind=icon}
|
|
|
|
|
||
AM Mayer, S Brenic and KB Glaser
Department of Pharmacology, Chicago College of Osteopathic Medicine, Downers Grove, Illinois, USA.
The purpose of this investigation was to pharmacologically probe the signaling pathways thought to be involved in protein kinase C (PKC)- stimulated superoxide anion (O2-) generation in all-trans retinoic acid- treated human promyelocytic HL-60 cell line (HL-60), targeting PKC, mitogen-activated protein kinase (MAPK), MAPK kinase (MEK), protein serine-threonine phosphatase(s) (PSP), protein tyrosine kinase(s) (PTK) and phosphatase(s) (PTP), secretory phospholipase A2, cyclooxygenase (CO) and 5-lipoxygenase with selected inhibitors. The following agents inhibited phorbol 12-myristate 13-acetate-stimulated O2- generation significantly in the all-trans retinoic acid-treated HL-60 cells (expressed as percentage of control, P < .05): 1) PKC inhibitors: staurosporine (100 nM, 3 +/- 1%); Ro 31-8220 (1 microM, 3 +/- 2%); sphingosine (100 microM, 15 +/- 7%); 2) PSP 1 and 2a inhibitors, okadaic acid (10 microM, 35 +/- 1%); calyculin A (10 microM, 73 +/- 1%); 3) MAPK inhibitor: SB-203580 (100 microM, 62 +/- 1%); 4) PTP inhibitors: phenylarsine oxide (1 microM, 12 +/- 9%); diamide (1 mM, 21 +/- 11%); and 5) secretory phospholipase A2 inhibitors: manoalide (1 microM, 24 +/- 10%); scalaradial (1 microM, 11 +/- 4%). Exogenously added arachidonic acid-stimulated O2- generation in a time- and dose- dependent manner. The following inhibitors enhanced or did not significantly affect phorbol 12-myristate 13-acetate-stimulated O2- generation (expressed as percentage of control): 1) PTK inhibitors: genistein (100 microM, 69 +/- 12%); CGP 53716 (100 microM, 67 +/- 10%); herbimycin A (10 microM, 67.4 +/- 1%); 2) PSP 2b inhibitors: cyclosporin A (30 microM, 71 +/- 5%); FK506 (30 microM, 88 +/- 7%); 3) CO inhibitor: indomethacin (100 microM, 111 +/- 12%); 4) 5-lipoxygenase inhibitor: WY 50,295 (100 microM, 140 +/- 23%); 5) MEK inhibitor: PD98059 (100 microM, 94 +/- 6.7%); and 6) the PTP inhibitor: orthovanadate (100 microM, 131 +/- 25%). Our pharmacological study suggests that, in neutrophil-like HL-60 cells, the signaling pathways leading to PMA-stimulated O2- generation appear to involve PKC, MAPK, phospholipase A2, arachidonic acid, PSP 1 and 2a and PTP. Furthermore, PTK, MEK, CO, 5-lipoxygenase and PSP 2b do not appear to participate in the modulation of PKC-stimulated O2- generation.
This article has been cited by other articles:
|
|
 |
|
  A. Zarbock and K. Ley Mechanisms and Consequences of Neutrophil Interaction with the Endothelium Am. J. Pathol., January 1, 2008; 172(1): 1 - 7. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. K.M. Wong, A. I. Pettit, P. A. Quinn, S. C. Jennings, J. E. Davies, and L. L. Ng Advanced Glycation End Products Stimulate an Enhanced Neutrophil Respiratory Burst Mediated Through the Activation of Cytosolic Phospholipase A2 and Generation of Arachidonic Acid Circulation, October 14, 2003; 108(15): 1858 - 1864. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A Perner, L Andresen, G Pedersen, and J Rask-Madsen Superoxide production and expression of NAD(P)H oxidases by transformed and primary human colonic epithelial cells Gut, February 1, 2003; 52(2): 231 - 236. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. Carpio, J. Gladu, D. Goltzman, and S. A. Rabbani Induction of osteoblast differentiation indexes by PTHrP in MG-63 cells involves multiple signaling pathways Am J Physiol Endocrinol Metab, September 1, 2001; 281(3): E489 - E499. [Abstract] [Full Text] [PDF]
|
|
 |
 |
 |
|
 |
 |
 |
