Cardiotoxins (CTXs), a major component of snake venom from Taiwan cobra Naja atra, are structurally homologues beta-sheet basic polypeptide, each types of CTXs exhibit different specificity toward different targets. CTX A3, CTXA2 and CTX A4 are interesting because of their strong ability and discrepancies in endocytosis and cytotoxicity. Besides CTX A2 and CTX A4 are dynamin-dependent and CTX A3 is dynamin-independent, Cholesterol also participates in endocytosis of CTXs. Cholesterol depletion thinning membrane facilitates CTX A3 to form pores. However cholesterol incorporation accelerates CTX A2 and CTX A4 to bind lipids and block CTX A3 to form pores. All three CTXs can dose-dependently decrease H9C2 viability and induce time-dependent apoptosis through receptor-mediated caspase-8 and mitochondrial-damaged caspase-9 pathways. Moreover CTXs induce calcium released from ER, but its function is still unknown because of inactivity of caspase-12. Although CTX A2 and CTX A4 differ only at the first amino acid residue, CTX A4 is more toxic and internalized than CTX A2. Moreover CTX A3 has a hydrophobic loop-2 binding phospholipids and breaks membrane, which is why CTX A3 is the most toxic and internalized for H9C2 cells. Most exciting result is observed that endocytosis is essential for toxicity. As blocking dynamin with dynasore, the results show that cytotoxicity of CTX A2 and CTX A4 was inhibited.

台灣眼鏡蛇毒蛋白主要成分中含有多種心臟毒素，各心臟毒素彼此結構相似且皆為beta-褶板正電性多肽；但各心臟毒素對於細胞的目標專一性不盡相同。由於心臟毒素中的A2、A3、A4能在短時間內進入細胞且產生毒性，故對心臟毒素A2、A3、A4之胞吞路徑與如何產生毒性感興趣。比較三者間進入細胞產生毒性的能力，發現A3最強，而A4次之。這有可能是進入細胞時，A3會造成膜穿孔而A2、A4須經由發動蛋白調控路徑有關。再者，細胞膜中的膽固醇含量亦會調控心臟毒素的胞吞作用，減少膽固醇有利於A3在膜上穿孔；而增加膽固醇會有效抑制A3穿孔，亦會促進A2及A4的胞吞。研究發現心臟毒素進入細胞後會攻擊粒線體及刺激內質網釋放鈣離子；故進一步觀察到caspase-8、9、12受心臟毒素攻擊而活化，進而對心肌細胞造成細胞凋亡。

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