Abstract
Abstract Cardiotoxins (CTXs) are the major component in the venom of Naja atra. They cause hemolysis, depolarization of cardiac muscle cells, and contraction of skeletal muscle. They also interrupt of the equilibrium of the ion channels, and exhibit various cytotoxicity effects. When one is bitten by a snake, the wound will induce inflammation and swelling,which will eventually lead to death. The immune system, including leukocytes and lymphocytes, is the most important defense mechanism in the human body. Among these different cells, neutrophils can migrate rapidly to the infected regions and kill the pathogens.In this work, we study the effects of CTX to the dosage of calcium of neutrophils. We found that CTX A2 can induce intracellular increase of calcium but not to the level that would cause the death of the cells. This increase is dependent on the dosage of CTX A2 but independent from extracellular dosage of calcium. We discover that CTX A2 has nothing to do with known signal transduction pathway. As a result, we infer this effect bears directly on the interaction between CTX A2 and the cell membrane. Comparing CTX A2 and CTX A4, we find that there is the only one structural difference in the first N-terminal amino acid sequence. The first N-terminal amino acid sequence of CTX A2 is Leu. In the view of cytotoxicity, CTX A4 is more toxic than CTX A2. But CTX A4 does not induce intracellular calcium increase in the real time calcium experiment. Therefore, modifying the N-terminal amino acid sequence of CTX A2 may clarify whether the N-terminal amino acid sequence is a possible factor to cause the intracellular calcium increase. We find that the deleted N-terminal Leu1 of CTX A2 dos not induce intracellular calcium increase. Thus we proved that the Leu1 of CTX A2 is the most crucial factor for intracellular calcium increase.