Background; The effects of FK506 on the endoplasmic reticulum (ER) mediated stress pathway accelerates CoCl2 – induced cytotoxicity in human hepatoma HepG2 cell line were investigated.

Methods; We examined the effects of FK506 on CoCl2 – induced cytotoxicity by western blottings of poly ADP-ribose polymerase(PARP), CHOP, GRP78, Nrf2, ATF4, ATF6, XBP-1, Bak, Bax, and Bcl-2. And the catalytic acitivity of caspase-3 and -12 caspase in HepG2 cells was also measured.

Results; FK506 and CoCl2 significantly induces the synergistic effect of HepG2 cytotoxicity in dose dependent manner. Increased active-PARP expression occurred at 24 hours after FK506 treatment on cobalt chloride-induced HepG2 cytotoxicity and peak activation of cleaved caspasec-3 was also observed at 24 hours. FK506 aggravates cobalt chloride-induced HepG2 cytotoxicity. GRP78 expression was increased 24 hours after FK506 treatment on cobalt chloride-induced HepG2 cytotoxicity. CHOP and caspase-12 expressions were increased 24 hours after FK506 treatment on cobalt chloride-induced HepG2 cytotoxicity. Expressions of ATF4 and ATF6 were same manners. Expression of XBP-1 was decreased beginning at 6 hours. FK506 exasperate endoplasmic reticulum stress by cobalt chloride-induced cytotoxicity. Bcl-2 protein expression decreased, but FK506 induces expression of Bak and Bax by cobalt chloride-induced cytotoxicity. Nrf2 expression was also noted.

Conclusions; FK506 and CoCl2 significantly induces the synergistic effect of cytotoxicity in dose dependent manner. FK506 aggravates cobalt chloride-induced cytotoxicity. FK506 exasperate endoplasmic reticulum stress by cobalt chloride-induced cytotoxicity. FK506 accelerates expression of ER-stress related nuclear transcriptional factor.

CITATION INFORMATION: Choi S, Chung S. CoCl2 Induced ER Stress Protein Mediated Cytotoxicity in FK506 Treated Hepatoma HepG2 Cells. Am J Transplant. 2016;16 (suppl 3).

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