Oxidative stress-induced up-regulation of the chloride channel and Na +/Ca2+ exchanger during cataractogenesis in diabetic rats

Kota V. Ramana, Deepak Chandra, Nancy K. Wills, Aruni Bhatnagar, Satish K. Srivastava

Research output: Contribution to journalArticle

15 Scopus citations

Abstract

We have determined the abundance of the chloride channel, ClC-3, and Na+/Ca2+ exchanger proteins in isolated rat lens cortex fiber cells by immunofluorescence method using polyclonal anti-ClC-3 antibodies and monoclonal antibodies against the canine cardiac Na+/Ca 2+ exchanger protein. These proteins were also quantified in the lens cortex of streptozotocin-injected rats by Western blots. Also, mRNA for ClC-3 was determined by Northern blot analysis. The isolated rat lens cortical fibers expressed basal levels of ClC-3 and Na+/Ca2+ exchanger proteins. As compared to controls, the ClC-3 protein in the lens cortex of diabetic rats (blood glucose>400 mg%) increased by 2.5-fold in 7 days and 4.5-fold in 14 days. However, the ClC-3 protein decreased to near-normal values in 40 days. The changes in ClC-3 mRNA closely followed the protein levels. Similarly, as compared to controls, on Day 7, the Na+/Ca2+ exchanger protein in the diabetic rat lens cortex increased by 3.5-fold and on Day14 by 5.5-fold. Subsequently, it decreased to control levels on Day 40. Treatment with the antioxidant, Trolox (2 mg/kg body weight), prevented the initial increase in ClC-3 and Na+/Ca2+ exchanger proteins. The up-regulation of ClC-3 and Na+/Ca2+ exchanger proteins during the early stages of diabetes and its prevention by antioxidants suggests that the proteins regulating ion transport may have a pathophysiological role in the development of diabetic cataracts.

Original languageEnglish (US)
Pages (from-to)177-182
Number of pages6
JournalJournal of Diabetes and Its Complications
Volume18
Issue number3
DOIs
StatePublished - May 1 2004

Keywords

  • Chloride channel
  • Diabetes
  • Fiber cells
  • Lens
  • Na/Ca exchanger

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism
  • Endocrinology

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