3-MCPD 1-Palmitate Induced Tubular Cell Apoptosis In Vivo via JNK/p53 Pathways

Man Liu1, Guoren Huang2, Thomas T Y Wang3

  • 1*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.

Insights

3-MCPD esters, food contaminants, induce kidney toxicity by activating the JNK/p53 pathway, leading to tubular cell apoptosis. This pathway is crucial for the observed nephrotoxicity.

Area of Science:

  • Toxicology
  • Molecular Biology
  • Food Safety

Background:

  • 3-chloro-1,2-propanediol (3-MCPD) esters are food processing contaminants.
  • Their nephrotoxicity is established, but the underlying molecular mechanisms are unclear.

Purpose of the Study:

  • To investigate the role of the JNK/p53 pathway in 3-MCPD ester-induced nephrotoxicity.
  • To elucidate the molecular mechanisms of kidney damage caused by 3-MCPD esters.

Main Methods:

  • Sprague Dawley rats were treated with 3-MCPD 1-palmitate (MPE).
  • Kidney gene expression was analyzed using microarray, qRT-PCR, and Western blot.
  • Apoptosis was assessed via histopathology, TUNEL, and immunohistochemistry.
  • p53 knockout and JNK/ERK inhibitors were used to confirm pathway involvement.

Main Results:

  • MPE altered mRNA expression of genes in JNK, ERK, p53, and apoptotic pathways.
  • These changes correlated with induced tubular cell apoptosis in rat kidneys.
  • p53 knockout attenuated MPE-induced apoptosis and related protein expression.
  • JNK inhibition, but not ERK inhibition, reduced MPE-induced apoptosis.

Conclusions:

  • The JNK/p53 pathway plays a critical role in 3-MCPD ester-induced tubular cell apoptosis.
  • This pathway is a key mediator of the nephrotoxicity associated with 3-MCPD esters and related compounds.

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