Chemical Dissection of the Link between Streptozotocin, O-GlcNAc, and Pancreatic Cell Death
2008

Understanding How Streptozotocin Causes Pancreatic Cell Death

publication Evidence: moderate

Author Information

Author(s): Pathak Shalini, Dorfmueller Helge C., Borodkin Vladimir S., van Aalten Daan M.F.

Primary Institution: Division of Biological Chemistry and Drug Discovery, College of Life Sciences, University of Dundee

Hypothesis

Does streptozotocin induce apoptosis in pancreatic cells through O-GlcNAc inhibition?

Conclusion

Streptozotocin induces apoptosis independently of its inhibition of O-GlcNAcase.

Supporting Evidence

  • Streptozotocin was shown to competitively inhibit O-GlcNAcase and induce apoptosis.
  • The galacto-configured derivative of streptozotocin did not inhibit O-GlcNAcase but still induced apoptosis.
  • Both streptozotocin and its derivative caused significant DNA fragmentation in pancreatic cells.

Takeaway

Streptozotocin is a chemical that can kill insulin-producing cells in the pancreas, and it does this in a way that doesn't depend on a specific process involving sugar molecules.

Methodology

The study used X-ray crystallography, enzymology, and cell biological studies on an insulinoma cell line to investigate the effects of streptozotocin and its derivatives.

Limitations

The study's findings may not fully account for all mechanisms of streptozotocin's action in vivo.

Digital Object Identifier (DOI)

10.1016/j.chembiol.2008.06.010

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