Midkine secretion protects Hep3B cells from cadmium induced cellular damage.
OBJECTIVE
To evaluate role of midkine secretion during Cadmium (Cd) exposure in the human hepatocyte cell line Hep3B cells.


METHODS
Different dosages of Cd (0.5-1-5-10 microg/mL) were applied to Hep3B cells and their effects to apoptosis, lactate dehydrogenase (LDH) leakage and midkine secretion were evaluated as time dependent manner. Same experiments were repeated with exogenously applied midkine (250-5000 pg/mL) and/or 5 microg/mL Cd.


RESULTS
Cd exposure induced prominent apoptosis and LDH leakage beginning from lower dosages at the 48th h. Cd induced midkine secretion with higher dosages (P < 0.001), (control, Cd 0.5-1-5-10 microg/mL respectively: 1123 +/- 73, 1157 +/- 63, 1242 +/- 90, 1886 +/- 175, 1712 +/- 166 pg/mL). Exogenous 500-5000 pg/mL midkine application during 5 microg/mL Cd toxicity prevented caspase-3 activation (control, Cd toxicity, 250, 500, 1000, 2500, 5000 pg/mL midkine+ Cd toxicity, respectively: 374 +/- 64, 1786 +/- 156, 1545 +/- 179, 1203 +/- 113, 974 +/- 116, 646 +/- 56, 556 +/- 63 cfu) LDH leakage and cell death in Hep3B cells (P < 0.001).


CONCLUSIONS
Our results showed that midkine secretion from Hep3B cells during Cd exposure protects liver cells from Cd induced cellular damage. Midkine has anti-apoptotic and cytoprotective role during Cd toxicity. Further studies are needed to explain the mechanism of midkine secretion and cytoprotective role of midkine during Cd exposure. Midkine may be a promising therapeutic agent in different toxic hepatic diseases.
Yazihan
Nuray
N
Molecular Biology Research and Development Unit, Faculty of Medicine, Ankara University, Morfoloji Binasi, Sihhiye, Ankara 06100,Turkey. nurayyazihan@yahoo.com
Ataoglu
Haluk
H
Akcil
Ethem
E
Yener
Burcu
B
Salman
Bulent
B
Aydin
Cengiz
C
D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D002104:Cadmium / Q000633:toxicity*; D006528:Carcinoma, Hepatocellular; D002455:Cell Division / Q000187:drug effects / Q000502:physiology; D045744:Cell Line, Tumor; D016207:Cytokines / Q000378:metabolism / Q000502:physiology*; D022781:Hepatocytes / Q000166:cytology* / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D008113:Liver Neoplasms; D000078792:Midkine
D016207:Cytokines; D002104:Cadmium; D000078792:Midkine