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Wednesday February 18th, 2009

The TRPV4 receptor plays a key role in the death of pancreatic cells induced by amyloid fibers

Anna Novials

Amyloid is a pathologic substance mostly consisting of proteins such as amylin, which can become deposited on different organs and tissues. In some degenerative diseases, such as Alzheimer’s or Parkinson’s, the formation of ordered amyloid fibers has been observed in places where cell death occurs. In patients with type-2 diabetes mellitus, islets of amyloid have been found within the islets of Langerhans, the collection of pancreatic cells with an endocrine function. These amyloid deposits are found in regions with cellular degeneration and have therefore been associated with the progression of the diabetes.

An IDIBAPS study published on the front page of Diabetologia (51(12):2252-62) by the team led by Dr. Anna Novials analyzes the mechanisms by which these amyloid fibers are associated with the death by apoptosis of pancreatic cells. The results show that abnormal concentrations of calcium play a key role in the toxicity induced by the amyloid. The hypothesis put forward in the article suggests that TRPV4, a channel to the cell surface that is sensitive to mechanical and osmotic changes, becomes activated in response to physical alterations caused by the aggregation of fibers around the cells. This would activate the process that leads to cell death by apoptosis: the entry of calcium into the cell, that the polarized nation of the membrane, and the activation of L-type calcium channels.

The study involved different experiments using pancreatic cells from MIN6 rats. The effect of different molecular experiments was analyzed and electron microscopy observations were carried out to show that the proximity of amyloid fibers leads to deformities in the pancreatic cells. Inhibition of TRPV4 by interference RNA resulted in a drastic reduction of alterations in the calcium concentration and prevented cell death. Although other mechanisms appear to be implicated, these experiments show that TRPV4 receptors play a key role in the initial stages of the process.

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