A lethal Cardiotoxic–Cytotoxic Protein from the Indian Monocellate Cobra (Naja kaouthia) Venom
IR@IICB: CSIR-Indian Institute of Chemical Biology, Kolkata
View Archive Info| Field | Value | |
| Title |
A lethal Cardiotoxic–Cytotoxic Protein from the Indian Monocellate Cobra (Naja kaouthia) Venom
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| Creator |
Debnath, Anindita
Saha, Archita Gomes, Antony Biswas, Sumit Chakrabarti, Pinakpani Giri, Biplab Biswas, Ajoy K Das Gupta, Shubho Gomes, Aparna |
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| Subject |
Drug Development/Diagnostics & Biotechnology
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| Description |
A lethal cardiotoxic–cytotoxic protein (mol. wt. 6.76 kDa) has been purified from the Indian
monocellate cobra (Naja kaouthia) venom by ion-exchange chromatography and HPLC. CD
spectra indicated the presence of 23% a helix, 19% b sheets and 35% coil. Complete amino
acid sequence was determined by MALDI, which showed similar homology with
cardiotoxins/cytotoxins isolated from venom of other Naja species. Intraperitoneal LD50
was 2.5 mg kg�1 in BalbC male mice. In vitro cardiotoxicity studies on isolated guinea pig
auricle showed that the molecule produced auricular blockade that was abolished after
trypsin treatment. Cytotoxicity studies on human leukemic U937 and K562 cells showed
that it significantly inhibited cell proliferation in a dose and time dependent manner, as
observed by trypan blue exclusion method and tetrazolium bromide reduction assay. IC50
on U937 and K562 cells were 3.5 mg/ml and 1.1 mg/ml respectively. Morphometry and cell
sorting studies indicated apoptosis induction in toxin treated leukemic cells. Apoptosis was
caspase 3 and 9 dependent and the treated leukemic cells were arrested in sub-G1 stage.
There was an increase in Bax–Bcl2 ratio, decrease in HSP (Heat shock protein) 70 and
HSP90 and induction of PARP cleavage after NK-CT1 treatment. The toxin showed low
cytotoxic effect on normal human leukocytes as compared with imatinib mesylate. Further
detailed cytotoxic and cardiotoxic effects at the molecular level are in progress.
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| Date |
2010
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| Type |
Article
PeerReviewed |
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| Format |
application/pdf
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| Identifier |
http://www.eprints.iicb.res.in/978/1/20_Toxicon_2010.pdf
Debnath, Anindita and Saha, Archita and Gomes, Antony and Biswas, Sumit and Chakrabarti, Pinakpani and Giri, Biplab and Biswas, Ajoy K and Das Gupta, Shubho and Gomes, Aparna (2010) A lethal Cardiotoxic–Cytotoxic Protein from the Indian Monocellate Cobra (Naja kaouthia) Venom. Toxicon, 56 (4). pp. 569-579. |
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| Relation |
http://dx.doi.org/10.1016/j.toxicon.2010.05.016
http://www.eprints.iicb.res.in/978/ |
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