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Article

Proteomic Analysis of the Mitochondrial Responses in P19 Embryonic Stem Cells Exposed to Florfenicol

by
Zhihua Dong
1,†,
Xueke Hou
1,†,
Xueying Wang
1,†,
Zihui Shen
1,
Huiqing Pang
1,
Lingli Chen
1,
Zhihong Yin
1,
Fei Ren
1,
Weiguo Li
2,
Yaming Ge
1,
Hongmei Ning
1,* and
Dongfang Hu
1,2,3,*
1
College of Animal Science and Technology, Henan Institute of Science and Technology, Xinxiang 453003, China
2
Postdoctoral Research Station in Biological Sciences, Henan Normal University, Xinxiang 453003, China
3
Postdoctoral Research and Development Base, Henan Institute of Science and Technology, Xinxiang 453003, China
*
Authors to whom correspondence should be addressed.
†
These authors have contributed equally to this work.
Toxics 2023, 11(12), 992; https://doi.org/10.3390/toxics11120992
Submission received: 16 November 2023 / Revised: 29 November 2023 / Accepted: 4 December 2023 / Published: 6 December 2023
(This article belongs to the Section Drugs Toxicity)
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Abstract

Florfenicol (FLO) has been shown to elicit diverse toxic effects in plants, insects, and mammals. Previously, our investigations revealed that FLO induced abnormal cardiac development and early embryonic mortality in chicken embryos. However, the effect of FLO on mitochondrial responses in stem cells remains unclear. In this study, we show that FLO significantly diminishes proliferation viability and obstructs the directed differentiation of P19 stem cells (P19SCs) into cardiomyocytes. Proteomic analysis revealed 148 differentially expressed proteins in response to FLO. Functional analysis has pinpointed FLO interference with biological processes associated with oxidative phosphorylation within the mitochondria. In alignment with the results of proteomic analysis, we confirmed that FLO inhibits the expression of both nuclear DNA-encoded and mitochondrial DNA-encoded subunits of the electron transport chain. Subsequent experiments demonstrated that FLO disrupts mitochondrial dynamics and induces the mitochondrial unfolded protein response to maintain mitochondrial homeostasis. These findings collectively highlight the significance of mitochondrial dynamics and the mitochondrial unfolded protein response to mediate the decreased proliferation viability and directed differentiation potential in P19SCs treated with FLO. In conclusion, this study provides a comprehensive overview of mitochondrial responses to FLO-induced cytotoxicity and enhances our understandings of the molecular mechanisms underlying FLO-induced embryonic toxicity.
Keywords: florfenicol; proteomic analysis; mitochondrial dynamics; embryonic toxicity florfenicol; proteomic analysis; mitochondrial dynamics; embryonic toxicity

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MDPI and ACS Style

Dong, Z.; Hou, X.; Wang, X.; Shen, Z.; Pang, H.; Chen, L.; Yin, Z.; Ren, F.; Li, W.; Ge, Y.; et al. Proteomic Analysis of the Mitochondrial Responses in P19 Embryonic Stem Cells Exposed to Florfenicol. Toxics 2023, 11, 992. https://doi.org/10.3390/toxics11120992

AMA Style

Dong Z, Hou X, Wang X, Shen Z, Pang H, Chen L, Yin Z, Ren F, Li W, Ge Y, et al. Proteomic Analysis of the Mitochondrial Responses in P19 Embryonic Stem Cells Exposed to Florfenicol. Toxics. 2023; 11(12):992. https://doi.org/10.3390/toxics11120992

Chicago/Turabian Style

Dong, Zhihua, Xueke Hou, Xueying Wang, Zihui Shen, Huiqing Pang, Lingli Chen, Zhihong Yin, Fei Ren, Weiguo Li, Yaming Ge, and et al. 2023. "Proteomic Analysis of the Mitochondrial Responses in P19 Embryonic Stem Cells Exposed to Florfenicol" Toxics 11, no. 12: 992. https://doi.org/10.3390/toxics11120992

APA Style

Dong, Z., Hou, X., Wang, X., Shen, Z., Pang, H., Chen, L., Yin, Z., Ren, F., Li, W., Ge, Y., Ning, H., & Hu, D. (2023). Proteomic Analysis of the Mitochondrial Responses in P19 Embryonic Stem Cells Exposed to Florfenicol. Toxics, 11(12), 992. https://doi.org/10.3390/toxics11120992

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