Role of drug transporters and heat shock proteins during ethanol exposure to human neural precursor cells and its lineages

• Published in: Tissue & cell Vol. 51; pp. 14 - 23
• Main Authors: Vishwakarma, Sandeep Kumar, Fatima, Nusrath, Lakkireddy, Chandrakala, Raju, Nagarapu, Bardia, Avinash, Sandhya, A., Paspala, Syed Ameer Basha, Satti, Vishnupriya, Khan, Aleem Ahmed
• Format: Journal Article
• Language: English
• Published: Scotland Elsevier Ltd 01-04-2018; Elsevier Science Ltd
• Subjects: ABC transporter; ABC transporters; ATP-Binding Cassette Transporters - biosynthesis; ATP-Binding Cassette Transporters - drug effects; Brain; Cell cycle; Cell Differentiation - drug effects; Cell growth; Cell Lineage - drug effects; Cell proliferation; Cell Proliferation - drug effects; Cell survival; Cell Survival - drug effects; Cells, Cultured; Central Nervous System Depressants - toxicity; Dendritic structure; Differentiation; Ethanol; Ethanol - toxicity; Ethanol exposure; Exposure; Gene expression; Heat shock proteins; HSP70 Heat-Shock Proteins - biosynthesis; HSP70 Heat-Shock Proteins - drug effects; Hsp70 protein; HSPs; Human behavior; Human exposure; Humans; Molecular chains; Molecular modelling; Nestin; Neural cell adhesion molecule; Neural Stem Cells - drug effects; Neural Stem Cells - metabolism; Neuronal deficits; Neurospheres; Overexpression; Oxidation-Reduction - drug effects; Phenotypic variations; Pluripotency; Precursors; Reactive oxygen species; Transcription; Transcriptome - drug effects; ABC transporters; Ethanol exposure; Neuronal deficits; HSPs
• ISSN: 0040-8166; 1532-3072
• DOI: 10.1016/j.tice.2018.02.001

•In vitro modelling of neurological deficits against ethanol exposure reveals involvement of several crucial mechanisms.•The in vitro culture model system developed herein provides more authentic proto-map to avoid diversity in stem cell pools.•This model offers better insight to design potential therapeutic strategies against ethanol-induced neurological damage.•ABC transporters and HSP70 provides neurological protection against ethanol-induced damage.
Ethanol exposure to developing brain may alter the growth and differentiation of neurological cells resulting in unfavorable pathologies. Earlier studies have provided very limited mechanistic insights of cellular and molecular mechanisms which do not mimic with human situation due to varying cell types and poses potential challenges for investigation. Therefore, the present study was undertaken to evaluate the role of ABC transporters and heat shock proteins mediated response in human neural precursor cells (NPCs) and its lineages during proliferation and lineage differentiation against ethanol exposure.
Effect of ethanol exposure was examined for neuronal cell survival and variation in cellular phenotype during neurospheres development and lineage differentiation. Generation of reactive oxygen species, and variation in cell cycle was identified along with transcriptional profiling for pluripotent markers (Nestin, NCAM, Sox-2, and Notch-2), drug transporters (ABCB1 and ABCG2) and stress protein (HSP70) during ethanol exposure.
ABC transporters as well as HSP70 mRNA expression was higher during proliferation as compared to differentiation with chronic ethanol (1 M) exposure (p < 0.01). Ethanol exposure resulted in higher variability in size and shape of developing neurospheres and decreased ability to form new neurosphere colonies. Significant changes were observed in dendrite development due to late ethanol exposure (p < 0.0001).
The present study demonstrated significant role of ABC transporters and HSP70 proteins in providing defense against ethanol-induced damage in human neurological cells. However, the over-expression of ABC transporter and HSP-70 proteins during such pathological conditions do not provide complete defense and additional strategies are required to repair the damage.