TY - JOUR
T1 - Type 2 Diabetes Induced by Changes in Proteomic Profiling of Zebrafish Chronically Exposed to a Mixture of Organochlorine Pesticides at Low Concentrations
AU - Gao, Yan
AU - Lee, Hyojin
AU - Lee, Sangkyu
AU - Kim, Ki Tae
N1 - Publisher Copyright:
© 2022 by the authors. Licensee MDPI, Basel, Switzerland.
PY - 2022/5/1
Y1 - 2022/5/1
N2 - Effect of organochlorine pesticides (OCPs) mixtures on development of type 2 diabetes mellitus (T2DM) and the underlying mechanism, especially at protein levels, are largely unknown. We exposed a mixture of five OCPs to zebrafish at concentrations of 0, 0.05, 0.25, 2.5, and 25 µg/L for 12 weeks. Differentially expressed proteins (DEPs) were quantitatively identified in female zebrafish livers, and its functional study was conducted. The significantly high glucose and low insulin levels were observed only at 0.05 µg/L, linking to the different pattern of DEPs than other concentrations. A total of 1082 proteins was quantified, of which 321 proteins formed 6 clusters in protein dynamics analysis. The enriched pathways in cluster 3 showing distinct pattern of DEPs could explain the nonlinear response at 0.05 µg/L, indicating that OCP mixtures adversely affected proteins associated with mitochondrial function and energy metabolism. We proposed a feasible mechanism that decrease in expression of aldehyde dehydrogenase led to abnormal accumulation of aldehydes, reducing expression of glyceraldehyde 3-phosphate dehydrogenase, and resulting in disruption of glucose homeostasis. Our findings help to better understand the causality of T2DM by exposure to OCP mixtures and to identify biomarkers in the protein expression level.
AB - Effect of organochlorine pesticides (OCPs) mixtures on development of type 2 diabetes mellitus (T2DM) and the underlying mechanism, especially at protein levels, are largely unknown. We exposed a mixture of five OCPs to zebrafish at concentrations of 0, 0.05, 0.25, 2.5, and 25 µg/L for 12 weeks. Differentially expressed proteins (DEPs) were quantitatively identified in female zebrafish livers, and its functional study was conducted. The significantly high glucose and low insulin levels were observed only at 0.05 µg/L, linking to the different pattern of DEPs than other concentrations. A total of 1082 proteins was quantified, of which 321 proteins formed 6 clusters in protein dynamics analysis. The enriched pathways in cluster 3 showing distinct pattern of DEPs could explain the nonlinear response at 0.05 µg/L, indicating that OCP mixtures adversely affected proteins associated with mitochondrial function and energy metabolism. We proposed a feasible mechanism that decrease in expression of aldehyde dehydrogenase led to abnormal accumulation of aldehydes, reducing expression of glyceraldehyde 3-phosphate dehydrogenase, and resulting in disruption of glucose homeostasis. Our findings help to better understand the causality of T2DM by exposure to OCP mixtures and to identify biomarkers in the protein expression level.
KW - aldehyde dehydrogenase 2
KW - glyceraldehyde 3-phosphate dehydrogenase
KW - organochlorine pesticide mixtures
KW - proteomics
KW - type 2 diabetes mellitus
KW - zebrafish
UR - http://www.scopus.com/inward/record.url?scp=85128396879&partnerID=8YFLogxK
U2 - 10.3390/ijerph19094991
DO - 10.3390/ijerph19094991
M3 - Article
C2 - 35564385
AN - SCOPUS:85128396879
SN - 1661-7827
VL - 19
JO - International Journal of Environmental Research and Public Health
JF - International Journal of Environmental Research and Public Health
IS - 9
M1 - 4991
ER -