Korean J Physiol Pharmacol.  2003 Jun;7(3):163-168.

Transduction of Tat-Superoxide Dismutase into Insulin-producing MIN6N Cells Reduces Streptozotocin-induced Cytotoxicity

• Choung IS
• Eum WS
• Li MZ
• Sin GS
• Kang JH
• Park J
• Choi SY
• Kwon HY

Abstract

The reactive oxygen species (ROS) are considered to be an important mediator in pancreatic beta cell destruction, thereby triggering the development of insulin-dependent diabetes mellitus. In the present study, HIV-1 Tat-mediated transduction of Cu, Zn-superoxide dismutase (SOD) was investigated to evaluate its protective potential against streptozotocin (STZ) -induced cytotoxicity in insulin-producing MIN6N cells. Tat-SOD fusion protein was successfully delivered into MIN6N cells in a dose-dependent manner and the transduced fusion protein was enzymatically active for 48 h. The STZ induced-cell destruction, superoxide anion radical production, and DNA fragmentation of MIN6N cells were significantly decreased in the cells pretreated with Tat-SOD for 1 h. Furthermore, the transduction of Tat-SOD increased Bcl-2 and heat shock protein 70 (hsp70) expressions in cells exposed to STZ, which might be partly responsible for the effect of Tat-SOD. These results suggest that an increased of free radical scavenging activity by transduction of Tat-SOD enhanced the tolerance of the cell against oxidative stress in STZ-treated MIN6N cells. Therefore, this Tat-SOD transduction technique may provide a new strategy to protect the pancreatic beta cell destruction in ROS-mediated diabetes.

Keyword

Diabetes; Tat-mediated transduction; Superoxide dismutase; ROS; Insulin-producing cells

MeSH Terms

Diabetes Mellitus, Type 1
DNA Fragmentation
HIV-1
HSP70 Heat-Shock Proteins
Insulin-Secreting Cells
Oxidative Stress
Reactive Oxygen Species
Streptozocin
Superoxide Dismutase
Superoxides
HSP70 Heat-Shock Proteins
Reactive Oxygen Species
Streptozocin
Superoxide Dismutase
Superoxides