AI Article Synopsis

  • Researchers found that necrosis primarily occurs in porcine renal tubular cells when exposed to high doses of cisplatin, with reactive oxygen species and TNF-alpha production being significant factors in this cell injury.
  • * The study also noted that both apoptosis and necrosis were observed in LLC-PK1 cells treated with cisplatin, indicating that both processes are involved in the renal damage caused by the drug.
  • * Specifically, apoptosis was linked to p53 activation and caspase involvement, while necrosis stemmed from oxidative stress and TNF-alpha production related to p38 MAPK signaling.

Article Abstract

We previously reported that necrosis occurs predominantly in porcine renal tubular LLC-PK1 cells, when the cells were exposed transiently to a high concentration of cisplatin. Moreover, we demonstrated that generation of reactive oxygen species and subsequent production of tumor necrosis factor-alpha (TNF-alpha) through phosphorylation of p38 MAPK are implicated in the pathogenesis of cisplatin-induced renal cell injury. However, some TUNEL-positive cells appeared in renal proximal tubules of rats after systemic injection of cisplatin, suggesting an involvement of apoptosis. In the present study, we found in LLC-PK1 cells that both apoptosis and necrosis were elicited when the cells were exposed to 200 microM cisplatin for 1 h followed by incubation for 24 h in the presence of 20 microM cisplatin. The cisplatin-induced necrosis was largely attenuated by the antioxidant N-acetylcysteine, while apoptosis was prevented by the specific inhibitors for caspases-2, -8, and -3 and a p53 inhibitor pifithrin-alpha but not by the p38 MAPK inhibitor SB203580. On the other hand, SB203580 attenuated the cisplatin-induced increase in TNF-alpha production. These findings suggest that p53-mediated activations of caspases-2, -8 and -3 play a key role in cisplatin-induced renal cell apoptosis, while oxidative stress-induced TNF-alpha synthesis via p38 MAPK phosphorylation contributed to the necrosis.

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Source
http://dx.doi.org/10.1007/s10495-007-0110-8DOI Listing

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