Understanding the implications of engineered nanoparticle induced autophagy in human epidermal keratinocytes in vitro

Engineered nanoparticles (NPs) such as TiO2 and ZnO are key UV-blocking ingredients in sunscreens. While toxicological risks of applying these materials are generally regarded as low due to minute levels of penetration across the skin, our understanding of the physiological influence of potential ce...

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Main Authors: Gautam, Archana, Rakshit, Moumita, Nguyen, Kim Truc, Kathawala, Mustafa Hussain, Nguyen, Luong Thi Hien, Tay, Chor Yong, Wong, Esther, Ng, Kee Woei
Other Authors: School of Materials Science & Engineering
Format: Article
Language:English
Published: 2020
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Online Access:https://hdl.handle.net/10356/139366
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Institution: Nanyang Technological University
Language: English
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spelling sg-ntu-dr.10356-1393662023-07-14T16:04:21Z Understanding the implications of engineered nanoparticle induced autophagy in human epidermal keratinocytes in vitro Gautam, Archana Rakshit, Moumita Nguyen, Kim Truc Kathawala, Mustafa Hussain Nguyen, Luong Thi Hien Tay, Chor Yong Wong, Esther Ng, Kee Woei School of Materials Science & Engineering School of Biological Sciences Environmental Chemistry and Materials Centre Nanyang Environment and Water Research Institute Science::Biological sciences Keratinocytes Sunscreen Engineered nanoparticles (NPs) such as TiO2 and ZnO are key UV-blocking ingredients in sunscreens. While toxicological risks of applying these materials are generally regarded as low due to minute levels of penetration across the skin, our understanding of the physiological influence of potential cell-nanoparticle interactions in the skin is limited. This study plugs the current knowledge gap by profiling TiO2 and ZnO NP interaction with primary human epidermal keratinocytes, based on potential levels of NP penetration across the skin. Specific attention was given to profiling real-life relevant levels of exposure, and accurate dosimetry measurements in vitro. ZnO was expectedly more cytotoxic than TiO2. Although both NPs generated Reactive Oxygen Species (ROS) and Mitochondrial Superoxide (MSO) within 4 h exposure to sub-lethal concentrations, ZnO induction of these oxidative stress markers increased much more significantly after 24 h exposure. Exposure to increasing NP concentrations increased autophagy induction along with activation of inflammatory responses in the keratinocytes, primarily through the TRAF6-mediated pathway. Sustained induction of autophagy led to degradation of TRAF6 and, only in the case of TiO2, reduced NF-κB activation. This pro-survival mode of autophagy induction provides further insights into the on-going debate on the use of these NPs in consumer products. Accepted version 2020-05-19T05:18:51Z 2020-05-19T05:18:51Z 2019 Journal Article Gautam, A., Rakshit, M., Nguyen, K. T., Kathawala, M. H., Nguyen, L. T. H., Tay, C. Y., . . ., Ng, K. W. (2019). Understanding the implications of engineered nanoparticle induced autophagy in human epidermal keratinocytes in vitro. NanoImpact, 15, 100177-. doi:10.1016/j.impact.2019.100177 2452-0748 https://hdl.handle.net/10356/139366 10.1016/j.impact.2019.100177 2-s2.0-85068852421 15 en NanoImpact © 2019 Elsevier B.V. All rights reserved. This paper was published in NanoImpact and is made available with permission of Elsevier B.V. application/pdf
institution Nanyang Technological University
building NTU Library
continent Asia
country Singapore
Singapore
content_provider NTU Library
collection DR-NTU
language English
topic Science::Biological sciences
Keratinocytes
Sunscreen
spellingShingle Science::Biological sciences
Keratinocytes
Sunscreen
Gautam, Archana
Rakshit, Moumita
Nguyen, Kim Truc
Kathawala, Mustafa Hussain
Nguyen, Luong Thi Hien
Tay, Chor Yong
Wong, Esther
Ng, Kee Woei
Understanding the implications of engineered nanoparticle induced autophagy in human epidermal keratinocytes in vitro
description Engineered nanoparticles (NPs) such as TiO2 and ZnO are key UV-blocking ingredients in sunscreens. While toxicological risks of applying these materials are generally regarded as low due to minute levels of penetration across the skin, our understanding of the physiological influence of potential cell-nanoparticle interactions in the skin is limited. This study plugs the current knowledge gap by profiling TiO2 and ZnO NP interaction with primary human epidermal keratinocytes, based on potential levels of NP penetration across the skin. Specific attention was given to profiling real-life relevant levels of exposure, and accurate dosimetry measurements in vitro. ZnO was expectedly more cytotoxic than TiO2. Although both NPs generated Reactive Oxygen Species (ROS) and Mitochondrial Superoxide (MSO) within 4 h exposure to sub-lethal concentrations, ZnO induction of these oxidative stress markers increased much more significantly after 24 h exposure. Exposure to increasing NP concentrations increased autophagy induction along with activation of inflammatory responses in the keratinocytes, primarily through the TRAF6-mediated pathway. Sustained induction of autophagy led to degradation of TRAF6 and, only in the case of TiO2, reduced NF-κB activation. This pro-survival mode of autophagy induction provides further insights into the on-going debate on the use of these NPs in consumer products.
author2 School of Materials Science & Engineering
author_facet School of Materials Science & Engineering
Gautam, Archana
Rakshit, Moumita
Nguyen, Kim Truc
Kathawala, Mustafa Hussain
Nguyen, Luong Thi Hien
Tay, Chor Yong
Wong, Esther
Ng, Kee Woei
format Article
author Gautam, Archana
Rakshit, Moumita
Nguyen, Kim Truc
Kathawala, Mustafa Hussain
Nguyen, Luong Thi Hien
Tay, Chor Yong
Wong, Esther
Ng, Kee Woei
author_sort Gautam, Archana
title Understanding the implications of engineered nanoparticle induced autophagy in human epidermal keratinocytes in vitro
title_short Understanding the implications of engineered nanoparticle induced autophagy in human epidermal keratinocytes in vitro
title_full Understanding the implications of engineered nanoparticle induced autophagy in human epidermal keratinocytes in vitro
title_fullStr Understanding the implications of engineered nanoparticle induced autophagy in human epidermal keratinocytes in vitro
title_full_unstemmed Understanding the implications of engineered nanoparticle induced autophagy in human epidermal keratinocytes in vitro
title_sort understanding the implications of engineered nanoparticle induced autophagy in human epidermal keratinocytes in vitro
publishDate 2020
url https://hdl.handle.net/10356/139366
_version_ 1773551396565549056