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ARS Home » Northeast Area » Beltsville, Maryland (BHNRC) » Beltsville Human Nutrition Research Center » Diet, Genomics and Immunology Laboratory » Research » Publications at this Location » Publication #323924
Title: 3-MCPD 1-palmitate induced renal tubular cell apoptosis in vivo via JNK/p53 pathway

Author
item LIU, MAN - Shanghai Jiaotong University
item HUANG, GUOREN - Shanghai Jiaotong University
item Wang, Thomas - Tom
item SUN, XIANGJUN - Shanghai Jiaotong University
item YU, LIANGLI - University Of Maryland

Submitted to: Toxicological Sciences
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 3/1/2016
Publication Date: 3/22/2016
Citation: Liu, M., Huang, G., Wang, T.T., Sun, X., Yu, L. 2016. 3-MCPD 1-palmitate induced renal tubular cell apoptosis in vivo via JNK/p53 pathway. Toxicological Sciences. 151(1):181-92. doi: 10.1093/toxsci/lfw033.

Interpretive Summary: Food contaminants can be from sources such as cooking oil. The fatty acid esters of 3-chloro-1, 2-propanediol (3-MCPD esters) are a group of processing-induced contaminants in cooking oil with nephrotoxicity, but the molecular mechanism(s) remain unclear. This study investigated whether and how the JNK/p53 pathway may play a role in the nephrotoxic effect of 3-MCPD esters using 3-MCPD 1-palmitate (MPE) as a probe compound in Sprague-Dawley rats. Microarray analysis of the kidney from the Sprague-Dawley rats treated with 3-MCPD 1-palmitate (MPE), using Gene Ontology categories and KEGG pathways, revealed that MPE altered mRNA expressions of the genes involved in the MAPK (JNK and ERK), p53 and apoptotic signal transduction pathways. The changes in the mRNA expressions were confirmed by qRT-PCR and western blot analyses, and were consistent with the induction of tubular cell apoptosis as determined by histopathological and TUNEL analyses in the kidneys of the Sprague-Dawley rats. Additionally, p53 knockout attenuated the apoptosis, and the apoptosis-related protein bax expression and cleaved caspase-3 activation induced by MPE in the p53 knockout C57BL/6 mice, whereas JNK inhibitor SP600125 but not ERK inhibitor U0126 inhibited MPE-induced apoptosis, supporting the conclusion that JNK/p53 might play a critical role in the tubular apoptosis induced by MPE and other 3-MCPD fatty acid esters. The study provides science-based toxicity information that can be use by translation scientist to refine processing method and for policy marker to develop regulation for food contaminants.

Technical Abstract: Fatty acid esters of 3-chloro-1, 2-propanediol (3-MCPD esters) are a group of processing-induced food contaminants with nephrotoxicity, but the molecular mechanism(s) remains unclear. This study investigated whether and how the JNK/p53 pathway may play a role in the nephrotoxic effect of 3-MCPD esters using 3-MCPD 1-palmitate (MPE) as a probe compound in Sprague-Dawley rats. Microarray analysis of the kidney from the Sprague-Dawley rats treated with 3-MCPD 1-palmitate (MPE), using Gene Ontology categories and KEGG pathways, revealed that MPE altered mRNA expressions of the genes involved in the MAPK (JNK and ERK), p53 and apoptotic signal transduction pathways. The changes in the mRNA expressions were confirmed by qRT-PCR and western blot analyses, and were consistent with the induction of tubular cell apoptosis as determined by histopathological and TUNEL analyses in the kidneys of the Sprague-Dawley rats. Additionally, p53 knockout attenuated the apoptosis, and the apoptosis-related protein bax expression and cleaved caspase-3 activation induced by MPE in the p53 knockout C57BL/6 mice, whereas JNK inhibitor SP600125 but not ERK inhibitor U0126 inhibited MPE-induced apoptosis, supporting the conclusion that JNK/p53 might play a critical role in the tubular apoptosis induced by MPE and other 3-MCPD fatty acid esters.