+ Site Statistics
+ Search Articles
+ PDF Full Text Service
How our service works
Request PDF Full Text
+ Follow Us
Follow on Facebook
Follow on Twitter
Follow on LinkedIn
+ Subscribe to Site Feeds
Most Shared
PDF Full Text
+ Translate
+ Recently Requested

Suppression of snake-venom cardiotoxin-induced cardiomyocyte degeneration by blockage of Ca2+ influx or inhibition of non-lysosomal proteinases



Suppression of snake-venom cardiotoxin-induced cardiomyocyte degeneration by blockage of Ca2+ influx or inhibition of non-lysosomal proteinases



Biochemical Journal 256(1): 89-95



The incubation of 10(5) single neonatal rat cardiomyocytes with 1 microM-cardiotoxin in a bath medium, Tyrode solution in the presence of 1 mM-Ca2+, at 37 degrees C evoked the following chain of events. Firstly, there appeared a latent period of about 10 min during which the cells behaved normally. Neither lactate dehydrogenase nor ATP leaked from the cells. Cytosolic free Ca2+ increased considerably, as measured by the fluorescence intensity of fura-2-Ca2+ complex. At the same time a large portion of endogenous ATP was depleted. Secondly, after the latent period, the cell beating became irregular and eventually stopped. Thirdly, blebs appeared on the cell surface, leading to cell degeneration. If, before the appearance of blebs, the cells were washed with the bath medium exhaustively or incubated in the presence of the toxin antibody, cytosolic free Ca2+ and endogenous ATP returned to normal levels and cells resumed regular beating. Preincubation of the cells with 3.75 microM-flunarizine or 3.75 microM-diltiazem (both are Ca2+ antagonists), or 1.5 microM-fura-2 acetoxymethyl ester (a chelate for Ca2+), or 200 microM-leupeptin or 50 microM-antipain (both are proteinase inhibitors) considerably suppressed the toxin's ability to degenerate the cells. On the other hand, lysosomal proteinase inhibitor, autophage inhibitor, serine proteinase inhibitor, phospholipase inhibitor and calmodulin antagonist did not inhibit the toxin's activity. The results suggest that the toxin may act on the extracellular surface of intact cardiomyocytes to increase cytosolic free Ca2+. The subsequent cell degeneration may result from the activation of a Ca2+-dependent non-lysosomal proteolytic system.

Please choose payment method:






(PDF emailed within 1 workday: $29.90)

Accession: 041492256

Download citation: RISBibTeXText

PMID: 3066344


Related references

Suppression of snake-venom cardiotoxin-induced cardiomyocyte degeneration by blockage of Ca 2+ influx or inhibition of non-lysosomal proteinases. Biochemical Journal 256(1): 89-95, 1988

Suppression of snake venom cardiotoxin induced cardiomyocyte degeneration by blockage of calcium influx or inhibition of non lysosomal proteinases. Biochemical Journal 256(1): 89-96, 1988

Inhibition of protein kinase C by snake venom toxins: comparison of enzyme inhibition, lethality and hemolysis among different cardiotoxin isoforms. Biochemistry and Molecular Biology International 35(5): 1103-1112, 1995

Activation of tissue phospholipases c and d by a snake venom cardiotoxin and bee venom melittin. Toxicon 30(5-6): 508, 1992

Snake venom cardiotoxin and bee venom melittin as tools to elucidate cellular lipid metabolism. Toxicon 31(2): 105-106, 1993

Effects of divalent cations on snake venom cardiotoxin-induced hemolysis and 3H-deoxyglucose-6-phosphate release from human red blood cells. Toxicon 27(12): 1297-1305, 1989

Effects of divalent cations on snake venom cardiotoxin induced hemolysis and tritiated deoxyglucose 6 phosphate release from human red blood cells. Toxicon 27(12): 1297-1306, 1989

Hemolytic activity of thionin from Pyrularia pubera nuts and snake venom toxins of Naja naja species: Pyrularia thionin and snake venom cardiotoxin compete for the same membrane site. Toxicon 27(5): 511-517, 1989

The crystal structure of the novel snake venom plasminogen activator TSV-PA: A prototype structure for snake venom serine proteinases. Structure 6(9): 1195-1206, 1998

Crystal structure of a snake venom cardiotoxin. Proceedings of the National Academy of Sciences of the United States of America 84(10): 3132-3136, 1987

Crystal structure of snake venom cardiotoxin. Proceedings of the National Academy of Sciences of the United States of America 84.10: 3132-3136, 1987

Crystal structure of snake venom cardiotoxin. Proceedings of the National Academy of Sciences of the United States of America 8410: 3132-3136, 1987

Conformational prediction for snake venom toxins and laser Raman scattering of a cardiotoxin from Taiwan cobra (Naja naja atra) venom. Biochemistry 16(13): 2999-3006, 1977

Snake venom cardiotoxin induces G-actin polymerization. Biochimica et Biophysica Acta 966(2): 266-268, 1988

Inhibition of invasion and metastasis of MHCC97H cells by expression of snake venom cystatin through reduction of proteinases activity and epithelial-mesenchymal transition. Archives of Pharmacal Research 34(5): 781-789, 2011