The cellular responses of autophagy, apoptosis, and 5-methylcytosine level in zebrafish cells upon nutrient deprivation stress.

Here we reported the stress responses of nutrient deprivation and extended observation of autophagy, apoptosis, and DNA methylation in zebrafish embryonic fibroblast (ZF4) cells. Our results showed that serum deprivation resulted in the changes of cell shape and adherent ability, the suppressed cell growth and viability, and the inhibited proliferation and cell cycle. Besides, the appearance of lysosome and autophagosome/autolysosome with significantly increased expression of mRNAs (ulk1a, becn1, atg12, sqstm1, maplc3, and lamp1) and proteins (Atg12, Becn1, Sqstm1, and Lamp1) indicate the autophagic activity was boosted at initial stage but relatively weakened at 48 h of serum starvation. When autophagy no longer mitigate for the stress, cell apoptosis detected by the mRNA expression of caspases, Bcl-2/Bax expression, and Annexin V/PI was gradually enhanced to execute the death plan upon prolonged starvation process. Furthermore, the methyl group metabolism was increased in accordance with autophagic activity and was suppressed by enhanced apoptotic activity. These data suggested that the recycle activity induced by autophagy could compensate the substrates and reactions of DNA transmethylation, which obviously increased 5-methylcytosine (5 mC) level in ZF4 cells. In summary, our results discovered the cellular responses under prolonged serum starvation stress and elaborated the switch from autophagy to apoptosis and corresponding correlation with 5 mC level changes in teleost fish in vitro.

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