This Article Full Text (PDF) References Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Alert me to new issues of the journal Add to Saved Citations Download to citation manager Add to My Marked Citations Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Citing Articles via Scopus Google Scholar Articles by Pala, I. Articles by Desaiah, D. Search for Related Content PubMed Articles by Pala, I. Articles by Desaiah, D. Social Bookmarking                         What's this?

Modulation of Calmodulin and Protein Kinase C Activities by Pencillium Mycotoxins

Department of Neurology, University of Mississippi Medical Center, 2500 North State Street, Jackson, Mississippi, USA

A. Srinivasan

Department of Biology, Tougaloo College, Tougaloo, Mississippi, USA

P. J. S. Vig

Department of Neurology, University of Mississippi Medical Center, 2500 North State Street, Jackson, Mississippi, USA

D. Desaiah

Department of Neurology, University of Mississippi Medical Center, 2500 North State Street, Jackson, Mississippi, USA

Calmodulin (CaM), a calcium-binding protein, is found in high concentrations in mammalian brain where it plays a pivotal role in a large number of cellular functions. Protein kinase C (PKC), a multifunctional cytosolic enzyme, in the presence of both Ca²⁺ and phospholipids, transduce extracellular signals into intracellu-lar events. Both CaM and PKC are partially involved in maintaining Ca²⁺ homeostasis in the cell. Any fluctuations in the intracel-lular Ca²⁺ can modulate cellular functions and may contribute to neuronal dysfunction. Hence, the present investigation was initiated to study the effects of some selected penicillium (naturally occurring tremorgenic) mycotoxins like secalonic acid, citreoviridin, and verruculogen on CaM activity, active conformation of CaM and PKC activity. Stimulation of CaM-deflcient bovine brain 3'-5' phosphodieste rase (PDE) indicated CaM activity. The modification of CaM active conformation was studied by the binding of fluorescent probe N-phenyl-1-napthylamine (NPN) to CaM. Alterations in the fluorescence of dansyl-CaM was used to study the effect of these compounds on complex formation between CaM and PDE. Rat brain cytosolic PKC was studied using ³²P-ATP as a measure of altered protein phosphorylation. The concentrations of mycotoxins used were in the range of 10 to 50 µM. All three mycotoxins inhibited CaM-stimulated PDE activity in a concentration-dependent manner. Citreoviridin and secalonic acid inhibited NPN fluorescence and Ca²⁺-dependent complex formation of dansyl-CaM and PDE. The IC50 values for NPN fluorescence of citreoviridin and secalonic acid were 13 µM and 19 µM respectively. However, verruculogen showed little effect on NPN fluorescence and the Ca²⁺-dependent complex formation of dansyl-CaM and PDE. These mycotoxins also inhibited PKC activity in a concentration-dependent manner with IC50 values of 19.8, 25.7, and 38.4 µM for secalonic acid, citreoviridin, and verruculogen, respectively. The results of our study suggest that these mycotoxins at very low concentrations are interacting with CaM and PKC. Such an effect could lead to impairment of neurotransmission and result in neurotoxicity.

Key Words: Calmodulin • Fluorescence • Neurotoxicity • Penicillium Mycotoxins • Protein Kinase C

International Journal of Toxicology, Vol. 18, No. 2, 91-96 (1999)
DOI: 10.1080/109158199225657


CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    Twitter    What's this?

This article has been cited by other articles:

				C. S Reddy Protein kinase C and chemical-induced abnormal palate development Human and Experimental Toxicology, April 1, 2005; 24(4): 203 - 214. [Abstract] [PDF]

				U. M. Hanumegowda, V. C. Dhulipala, and C. S. Reddy Mechanism of Secalonic Acid D-Induced Inhibition of Transcription Factor Binding to Cyclic AMP Response Element in the Developing Murine Palate Toxicol. Sci., November 1, 2002; 70(1): 55 - 62. [Abstract] [Full Text] [PDF]