Hexavalent Chromium Induces Apoptosis and Autophagy in Human Neurons and Astrocytes via MAPK Pathway Activation
Issued Date
2026-01-01
Resource Type
ISSN
01634984
eISSN
15590720
Scopus ID
2-s2.0-105034866275
Journal Title
Biological Trace Element Research
Rights Holder(s)
SCOPUS
Bibliographic Citation
Biological Trace Element Research (2026)
Suggested Citation
Phuagkhaopong S., Sukprasert R., Settacomkul R., Ospondpant D., Suknuntha K., Khemawoot P., Power C., Vivithanaporn P. Hexavalent Chromium Induces Apoptosis and Autophagy in Human Neurons and Astrocytes via MAPK Pathway Activation. Biological Trace Element Research (2026). doi:10.1007/s12011-026-05046-0 Retrieved from: https://repository.li.mahidol.ac.th/handle/123456789/116149
Title
Hexavalent Chromium Induces Apoptosis and Autophagy in Human Neurons and Astrocytes via MAPK Pathway Activation
Corresponding Author(s)
Other Contributor(s)
Abstract
Hexavalent chromium (Cr[VI]), one of the major heavy metals in fine particulate matter (PM<inf>2.5</inf>), has been linked to increased risks of neurological impairment and brain cancer. However, the direct effect of Cr(VI) on brain cells remains unclear. In this study, we investigated the cell type–specific cytotoxicity of Cr(VI) at environmentally relevant concentrations to cultured human neurons and astrocytes. Our findings showed that higher concentrations of Cr(VI) were required to induce cell death in human astrocytes (IC<inf>50</inf> of 32.05 µM at 24 h) than in the human neurons (IC<inf>50</inf> of 24.55 µM at 24 h). The neurotoxicity effects associated with elevated intracellular chromium levels included DNA damage (decreased poly[ADP–ribose] polymerase expression), mitochondria-mediated apoptosis (increased caspase 3/7 activation), and autophagy (increased light chain 3 [LC3]–II to LC3–I levels accompanied by decreased p62 expression). Activation of the MAPK signalling pathway triggered Cr(VI) –induced brain death. Furthermore, Cr(VI) exposure induced S–phase accumulation in U-87 MG cells by altering cell cycle–related protein expression, specifically by upregulating CDK inhibitors (p21, p27, and p53) and downregulating cyclin B, cyclin D, and CDK4. Together, these findings demonstrate that the mechanisms underlying Cr(VI)-induced neurotoxicity were similar between the two cell types and further highlight the importance of increased awareness of chromium pollution and its impact on human health.