Prevention of free-radical induced apoptosis by induction of human recombinant Cu, Zn-SOD in pig endothelial cells.

Vascular endothelial cells are the prime target in ischemia reperfusion injury. Growing evidence has shown that one of the main etiologies is considered to be reactive oxygen species (ROS) that induce endothelial-cell death either by necrosis or apoptosis. Cultured porcine endothelial cells were transfected with human copper, zinc-superoxide dismutase (h-Cu, Zn-SOD) to investigate whether these cells can prevent apoptosis from oxidative injury in vitro. The endothelial cells were cultured with SIN-1 (3-morpholinosydnonimine-N-ethylcarbanride) as a donor of peroxinitrite (ONOO(-)). The control cells without the gene transfection developed characteristic apoptotic changes both morphologically and biochemically when they were incubated with SIN-1 of 200 M. However, the cells showed necrosis predominantly when the concentration of SIN-1 was 1,000 M. On the other hand, the cells transfected with h-Cu, Zn-SOD showed significantly less evidence of apoptotic change after exposure to SIN-1. Nitric oxide (NO) did not significantly affect the viability of either the control cells or the transfected cells. One of the potent ROS, peroxinitrite, is considered to play a significant role in ischemia reperfusion injury. SIN-1 can produce peroxinitrite in vitro that induces endothelial-cell damage by apoptosis. This type of cytotoxicity can be successfully prevented by transfection of the h-Cu, Zn-SOD into the cells.

Citation

Itsuo Yokoyama, Masataka Negita, Da-Ge Liu, Takaharu Nagasaka, Takaaki Kobayashi, Akemi Hayakawa, Shuji Hayashi, Akimasa Nakao. Prevention of free-radical induced apoptosis by induction of human recombinant Cu, Zn-SOD in pig endothelial cells. Transplant international : official journal of the European Society for Organ Transplantation. 2002 May;15(5):220-5

Mesh Tags

Substances

PMID: 12012042

search → result