Upregulations of Clcn3 and P-Gp Provoked by Lens Osmotic Expansion in Rat Galactosemic Cataract.

Abstract

OBJECTIVE:

Lens osmotic expansion, provoked by overactivated aldose reductase (AR), is the most essential event of sugar cataract. Chloride channel 3 (Clcn3) is a volume-sensitive channel, mainly participating in the regulation of cell fundamental volume, and P-glycoprotein (P-gp) acts as its modulator. We aim to study whether P-gp and Clcn3 are involved in lens osmotic expansion of galactosemic cataract.

METHODS AND RESULTS:

In vitro, lens epithelial cells (LECs) were primarily cultured in gradient galactose medium (10-60 mM), more and more vacuoles appeared in LEC cytoplasm, and mRNA and protein levels of AR, P-gp, and Clcn3 were synchronously upregulated along with the increase of galactose concentration. In vivo, we focused on the early stage of rat galactosemic cataract, amount of vacuoles arose from equatorial area and scattered to the whole anterior capsule of lenses from the 3rd day to the 9th day, and mRNA and protein levels of P-gp and Clcn3 reached the peak around the 9th or 12th day.

CONCLUSION:

Galactosemia caused the osmotic stress in lenses; it also markedly leads to the upregulations of AR, P-gp, and Clcn3 in LECs, together resulting in obvious osmotic expansion in vitro and in vivo.

• Authors: Lixia Ji, Lixia Cheng, Zhihong Yang
• Journal: Journal of diabetes research (J Diabetes Res) Vol. 2017 Pg. 3472735 ( 2017) ISSN: 2314-6753 [Electronic] England
• PMID: 29527534 (Publication Type: Journal Article)

Chemical References

• ATP Binding Cassette Transporter, Subfamily B, Member 1
• Chloride Channels
• ClC-3 channel
• Aldehyde Reductase
• Galactose

Topics

• ATP Binding Cassette Transporter, Subfamily B, Member 1 (genetics, metabolism)
• Aldehyde Reductase (genetics, metabolism)
• Animals
• Cataract (genetics, metabolism)
• Cells, Cultured
• Chloride Channels (genetics, metabolism)
• Diabetes Complications (genetics, metabolism)
• Dogs
• Galactose (pharmacology)
• Lens, Crystalline (cytology, drug effects, metabolism)
• Male
• Osmotic Pressure (drug effects)
• Rats
• Rats, Sprague-Dawley
• Up-Regulation