title: 3-MCPD 1-Palmitate Induced Tubular Cell Apoptosis In Vivo via JNK/p53 Pathways.
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 MPE, using Gene Ontology categories and KEGG pathways, revealed that MPE altered mRNA expressions of the genes involved in the mitogen-activated protein kinase (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, TUNEL, and immunohistochemistry 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 cell apoptosis induced by MPE and other 3-MCPD fatty acid esters.
authors.affiliation: *Institute of Food and Nutraceutical Science, School of Agriculture & Biology, Shanghai Jiao Tong University, Shanghai 200240, China Beijing Advanced Innovation Center for Food Nutrition and Human Health, Beijing Technology & Business University (BTBU), Beijing 100048, China.
authors.forename: Man
authors.initials: M
authors.lastname: Liu
authors.affiliation: *Institute of Food and Nutraceutical Science, School of Agriculture & Biology, Shanghai Jiao Tong University, Shanghai 200240, China.
authors.forename: Guoren
authors.initials: G
authors.lastname: Huang
authors.affiliation: Diet, Genomics, and Immunology Laboratory, Agricultural Research Service (ARS), Beltsville, MD 20705.
authors.forename: Thomas T Y
authors.initials: TT
authors.lastname: Wang
authors.affiliation: *Institute of Food and Nutraceutical Science, School of Agriculture & Biology, Shanghai Jiao Tong University, Shanghai 200240, China.
authors.forename: Xiangjun
authors.initials: X
authors.lastname: Sun
authors.affiliation: *Institute of Food and Nutraceutical Science, School of Agriculture & Biology, Shanghai Jiao Tong University, Shanghai 200240, China Department of Nutrition and Food Science, University of Maryland, 0112 Skinner Building, College Park, MD 20742 lyu5@umd.edu.
authors.forename: Liangli Lucy
authors.initials: LL
authors.lastname: Yu
mesh_terms: D058186:Acute Kidney Injury / Q000139:chemically induced* / Q000201:enzymology / Q000235:genetics / Q000473:pathology; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D020869:Gene Expression Profiling / Q000379:methods; D048031:JNK Mitogen-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism*; D007684:Kidney Tubules / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology; D008297:Male; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D050178:Monoglycerides / Q000633:toxicity*; D020411:Oligonucleotide Array Sequence Analysis; D010168:Palmitates / Q000633:toxicity*; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects; D013997:Time Factors; D016159:Tumor Suppressor Protein p53 / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*
chemical_list: C000625943:3-chloro-1,2-propanediol 1-palmitate; D050178:Monoglycerides; D010168:Palmitates; D016159:Tumor Suppressor Protein p53; D048031:JNK Mitogen-Activated Protein Kinases
keywords: ERK.; JNK; acute tubular cell injury; apoptosis; p53