MALVINA BONI MITAKE
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Resumo IPEN-doc 23864 Crotamine toxicity revisited: novel insights based on KV channel inhibition2012 - TYTGAT, JAN; PEIGNEUR, STEVE; BELATO Y ORTS, DIEGO J.; SILVA, ALVARO P. da; OGUIURA, NANCY; BONI-MITAKE, MALVINA; ZAHARENKO, ANDRE J.Crotamine, a 5KDa peptide possesses a unique biological versatility. Not only its cell-penetrating activity has become of clinical interest but moreover, its potential selective anti-tumor activity is of great pharmacological importance. Before, several studies have attempted to elucidate the exact molecular target responsible for the crotamine-induced skeletal muscle spasm. The aim of this study was to investigate whether crotamine affects voltage-gated potassium (KV) channels in an effort to explain its in vivo effects. Crotamine was studied on ion channel function using the two-electrode voltage clamp technique on 16 cloned ion channels (12 KV channels and 4 NaV channels), expressed in Xenopus laevis oocytes. Crotamine selectively inhibits KV1.1, KV1.2 and KV1.3 channels with an IC50 of ~300 nM and the key amino acids responsible for this molecular interaction are highlighted. Our results demonstrate for the first time that the symptoms which are observed in the typical crotamine syndrome may result from the inhibition of KV channels. The ability of crotamine to inhibit the potassium current through KV channels unravels it as the first snake peptide with the unique multifunctionality such as cell penetrating, antitumoral activity and KV channel inhibiting properties. The potent and selective KV channel inhibiting properties, as demonstrated in this work, can be an advantage for the use of crotamine or its derivatives as antitumor drug. This new property of crotamine might explain some experimental observations and opens new perspectives of pharmacological uses.Artigo IPEN-doc 18847 Crotamine pharmacology revisted: Novel insights based on the inhibition of Ksub(v) channels2012 - PEIGNEUR, STEVE; ORTS, DIEGO J.B.; SILVA, ALVARO R.P da; OGUIURA, NANCY; BONI-MITAKE, MALVINA; OLIVEIRA, EDUARDO B. de; ZAHARENKO, ANDRE J.; FREITAS, JOSÉ C. de; TYTGAT, JAN