PKC activation by melatonin modulates vimentin intermediate filament organization in N1E‐115 cells

Abstract

Melatonin enters cells and causes cytoskeletal rearrangements in unicellular organisms, plants and vertebrates. This pineal secretory product causes microtubule enlargement and neurite outgrowth by a calmodulin antagonism in N1E-115 cells. Recently, direct in vitro activation of protein kinase C by melatonin was described. Vimentin intermediate filaments are attached to microtubules and their organization depends on both microtubule distribution and phosphorylation of specific proteins. Protein kinase C is a serine threonine kinase which phosphorylates vimentin and through this mechanism causes intermediate filament disassembly. In this work the effects of melatonin on protein kinase C activation, content, and subcellular distribution were studied in N1E-115 cells. Also, melatonin effects on vimentin phosphorylation and subcellular distribution were explored. The results show that melatonin both activates and increases protein kinase C content in the membrane cytoskeletal fraction. Melatonin protein kinase C activation was followed by an increase in both vimentin phosphorylation and by vimentin subcellular redistribution. Moreover, staurosporine, a serine threonine kinase inhibitor, prevented increased vimentin phosphorylation elicited by melatonin. Similar effects to those caused by melatonin were obtained with the protein kinase C activator phorbol 12-myristate 13-acetate. Data support the idea that melatonin modulates vimentin organization through protein kinase C activation.

Cleavage of p53-Vimentin Complex Enhances Tumor Necrosis Factor-Related Apoptosis-Inducing Ligand-Mediated Apoptosis of Rheumatoid Arthritis Synovial Fibroblasts

“…In addition, it is likely that vimentin cleavage also regulates apoptosis of RASFs in a p53-independent manner because vimentin regulates organization of cytoplasmic structure, 61 cell migration and response to mechanical stress, 62 membrane trafficking, granular secretion, protein kinase activation, and regulation of stress response proteins. 63 The present results suggest, however, that the major affect of vimentin in regulation of apoptosis after DR5 signaling is the release of p53, which can be significantly inhibited by expression of mutant vimentin, blocking of caspase-4 activation, or blocking of p53 function.…”

Melatonin, Mitochondrial Homeostasis and Mitochondrial-Related Diseases

“…In addition, the expression of some genes, mainly related to the cell redox and inflammatory responses including GPx, GRd, SOD, inducible nitric oxide synthase (iNOS) and cytokines are also under genomic regulation by melatonin [76][77][78]. In addition, the specific binding of melatonin to Ca 2+ -calmodulin (CaCaM) appears to regulate some CaCaMdependent enzymes such as nNOS [79,80]. The recent discovery of the mitochondrion being a target for melatonin action opens new perspectives to understand the mechanism of action of melatonin, and may help to explain the antiapoptotic and thermogenic effects of the indoleamine [81,82].…”

Melatonin, mitochondria, and cellular bioenergetics

“…High-affinity binding of melatonin to CaM has been characterized [Romero et al, 1998]. The significance of melatonin -CaCaM interaction was emphasized in a series of experiments showing changes in the cytoskeletal rearrangements due to this interaction [Benítez-King, 2000]. Also, the binding of melatonin to CaCaM inhibits intracellular CaCaM-dependent enzymes, such as NOS .…”