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ML-7 Inhibits Exocytosis of Superoxide-Producing Intracellular Compartments in Human Neutrophils Stimulated With Phorbol Myristate Acetate in a Myosin Light Chain Kinase-Independent Manner

ML-7 Inhibits Exocytosis of Superoxide-Producing Intracellular Compartments in Human Neutrophils Stimulated With Phorbol Myristate Acetate in a Myosin Light Chain Kinase-Independent Manner

Keita Odani, Toshihiro Kobayashi, Yasuhiro Ogawa, Shoji Yoshida, Harumichi Seguchi

Histochem Cell Biol. 2003 May;119(5):363-70.

PMID: 12750906

Abstract:

ML-7, (5-iodonaphthalene-1-sulfonyl) homopiperazine, is commonly employed as a myosin light chain kinase (MLCK) inhibitor. In the present study, we demonstrated that ML-7 affects the superoxide (O(2)(-))-producing system of human neutrophils in an MLCK-independent manner. Human neutrophils were stimulated with phorbol myristate acetate (PMA), which does not activate MLCK. ML-7 inhibited extracellular release, but not intracellular production of O(2)(-) in the stimulated cells. Fluorescence microscopy revealed the generation of O(2)(-) at intracellular compartments in the stimulated cells exposed to ML-7. At the electron microscopic level, the reaction product of NADPH oxidase activity was found in intracellular compartments. ML-7 strongly inhibited the association of the oxidant-producing intracellular compartments with the plasma membrane. Furthermore, the upregulation of alkaline phosphatase activity, a marker enzyme of the oxidant-producing intracellular compartments, was also inhibited by ML-7. These findings indicate that ML-7 inhibits the fusion of the oxidant-producing intracellular compartments to the plasma membrane resulting in the inhibition of the extracellular release of O(2)(-) in PMA-stimulated human neutrophils in an MLCK-independent manner.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP110448334-A	ML-7		110448-33-4	Price

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