On the mechanism of apoptosis-inducing activity of human calprotectin: zinc sequestration, induction of a signaling pathway, or something else?
Calprotectin, a heterodimer present in neutrophil cytoplasm, has antimicrobial and apoptosis-inducing activities. At the moment, there are two general hypotheses about the mechanism of action of calprotectin: (i) exclusion of extracellular zinc by calprotectin, and consequently induction of apoptosis; (ii) binding of calprotectin to a cell membrane receptor, and consequently, activation of a signaling pathway for apoptosis. Here, we introduce another hypothesis, i.e. inhibition or destruction of "target" inside cells. We suggest that calprotectin might become internalized non-specifically, maybe in a process like pinocytosis. This process is probably independent of the zinc concentration. We also demonstrated that the internal target hypothesis successfully predicts cell survival behavior of cultured cells as a function of calprotectin concentration. Additional analyses should be performed to elucidate the real calprotectin "target".
Zali
Hakimeh
H
National Cell Bank of Iran, Pasteur Institute of Iran, Tehran, Iran.
Marashi
Sayed-Amir
SA
Rezaei-Tavirani
Mostafa
M
Toossi
Parviz
P
Rahmati-Roodsari
Mohammad
M
Shokrgozar
Mohammad Ali
MA
D000230:Adenocarcinoma / Q000473:pathology; D017209:Apoptosis / Q000187:drug effects*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D006801:Humans; D039841:Leukocyte L1 Antigen Complex / Q000494:pharmacology*; D008954:Models, Biological; D015398:Signal Transduction / Q000187:drug effects*; D013274:Stomach Neoplasms / Q000473:pathology; D013997:Time Factors; D015032:Zinc / Q000378:metabolism*
D039841:Leukocyte L1 Antigen Complex; D015032:Zinc