Work

Two-Dimensional Layered Nano-MoS2 Induces Earthworm Immune Cell Apoptosis by Regulating Lysosomal Maintenance and Function: Toward Unbiased Screening and Validation of Suspicious Pathways

Year: 2024

Type: article

Abstract: Molybdenum-based nanosheets (NSMoS 2 ) are increasingly applied in various fields and undergoing relevant risk evaluations on subjectively hypothesized toxicity pathways. However, risk assessment should be unbiased and focus on appropriate end points to avoid biased prescreening. Here, we developed an adverse biological outcome screening strategy based on nontargeted functional protein profiles in earthworm ( Eisenia fetida ) immune cells exposed to NSMoS 2 and their ionic counterpart (Na 2 MoO 4 ). Through this framework, the apoptosis-related processes with distinct mechanisms were rapidly identified and thoroughly validated phenotypically. Specifically, upon exposure to 50 μg Mo/mL Na 2 MoO 4, cellular signaling and energy homeostasis were disrupted within the transcription–translation biological chain. The autophagic pathway was activated, which, together with energy deprivation, phenotypically induced significant autophagy that ultimately led to apoptosis. In contrast, NSMoS 2, tested at the same concentration, caused a reprogramming of apoptotic gene and protein expressions. Transcriptome plasticity facilitated the endocytic-adaptive transcriptional profile characterized by cytoskeleton remodeling and lysosome organization/movement under NSMoS 2 exposure. Subcellular dynamics further revealed NSMoS 2 -induced lysosomal damage with a time-sensitive physiological window, ultimately mediating apoptosis. These findings provide a mechanistic and visual understanding of the distinct risk profile of NSMoS 2 compared to molybdate, highlighting the importance of integrating nontargeted screening and phenotypic validation in early risk warning.

Source: Environmental Science & Technology

DOI: 10.1021/acs.est.4c04512

Authors: Kailun Sun, Cornelis A. M. van Gestel, Hao Qiu

Institutions: Shanghai Jiao Tong University, Vrije Universiteit Amsterdam

Language: English

Topic: Environmental Toxicology and Ecotoxicology

Subfield: Health, Toxicology and Mutagenesis

Field: Environmental Science

Domain: Physical Sciences

Open Access status: green

Funders: Shanghai Tongji Gao Tingyao Environmental Science and Technology Development Foundation, National Natural Science Foundation of China, National Key Research and Development Program of China

Awards: G3264859511, G8015461255, G8832035269