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Cathepsins D and L reduce the toxicity of advanced glycation end products

Stefanie Grimm1, Melanie Horlacher, Betül Catalgol

  • 1Institute of Nutrition, Friedrich Schiller University Jena, 07743 Jena, Germany.

Free Radical Biology & Medicine
|January 17, 2012
PubMed

Insights

Advanced glycation end products (AGEs) are taken up by cells and degraded by lysosomal proteases, cathepsins D and L. These cathepsins are crucial for reducing AGE-induced cellular damage.

Area of Science:

  • Cell Biology
  • Biochemistry
  • Aging Research

Background:

  • Advanced glycation end products (AGEs) accumulate with aging and in diseases like diabetes.
  • The intracellular fate and degradation of AGEs, particularly via lysosomal pathways, are not well understood.
  • Lysosomal function is known to decline during aging, potentially leading to cellular material accumulation.

Purpose of the Study:

  • To investigate the degradation of AGEs within the endosomal-lysosomal system.
  • To determine if impaired lysosomal proteases contribute to AGE accumulation.
  • To examine the role of cathepsins D and L in AGE-induced cytotoxicity.

Main Methods:

  • Generation of five distinct types of AGEs using bovine serum albumin and various sugars/aldehydes.
  • Assessment of AGE uptake by the macrophage cell line RAW 264.7.
  • Measurement of cathepsin D and L activity and maturation.
  • Quantification of lysosomes using LysoTracker blue staining.
  • Evaluation of AGE-induced cytotoxicity in cathepsin D and L knockout cells.

Main Results:

  • RAW 264.7 cells effectively internalized AGEs.
  • AGE exposure led to increased activity and maturation of cathepsins D and L.
  • The number of lysosomes within cells increased upon AGE exposure.
  • Cathepsins D and L were found to be essential for mitigating AGE-induced cytotoxicity.

Conclusions:

  • The endosomal-lysosomal system, specifically cathepsins D and L, plays a role in AGE degradation.
  • Increased cathepsin activity and lysosome biogenesis are cellular responses to AGEs.
  • Both cathepsins D and L are necessary to reduce the toxic effects of AGEs on cells.

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