Intracellular ROS levels determine the apoptotic potential of keratinocyte by Quantum Dot via blockade of AKT Phosphorylation.
Eun Young LeeHyun Cheol BaeHana LeeYeonsue JangYoon-Hee ParkJin Hee KimWoo-In RyuByeong Hyeok ChoiJi Hyun KimSang Hoon JeongSang Wook SonPublished in: Experimental dermatology (2017)
Quantum dots (QDs) have shown great potential for biomedical use in a broad range including diagnostic agents. However, the regulatory mechanism of dermal toxicity is poorly understood. In this study, we investigated how QDs-induced apoptosis is regulated in human keratinocytes. We also examined the effect of carboxylic acid-coated QDs (QD 565 and QD 655) on reactive oxygen species (ROS) production and apoptosis-related cellular signalling. The viability of keratinocyte was inhibited by two types of QDs in a concentration-dependent manner. QDs induce ROS production and blockade of AKT phosphorylation. Moreover, the cleavage of AKT-dependent pro-apoptotic proteins such as poly (ADP-ribose) polymerase, caspases-3 and caspases-9 was significantly increased. We also found that a decrease in cellular ROS level by ROS scavenger, N-acetylcysteine (NAC), resulting in the abolishment of QDs-induced AKT de-phosphorylation and cellular apoptosis. Interestingly, QD 655 had a more cytotoxic effect including oxidative stress and AKT-dependent apoptosis than QD 565. In addition, QD 655 had the cytotoxic potential in the human skin equivalent model (HSEM). These data show that QD-induced intracellular ROS levels may be an important parameter in QD-induced apoptosis. These findings from this study indicate that intracellular ROS levels might determine the apoptotic potential of keratinocyte by QD via blockade of AKT phosphorylation.
Keyphrases
- reactive oxygen species
- cell death
- induced apoptosis
- oxidative stress
- signaling pathway
- endoplasmic reticulum stress
- dna damage
- diabetic rats
- cell cycle arrest
- cell proliferation
- pi k akt
- quantum dots
- transcription factor
- endothelial cells
- ischemia reperfusion injury
- high glucose
- anti inflammatory
- protein kinase
- electronic health record