Nicotinamide blocks N-methyl-N-nitrosourea-induced photoreceptor cell apoptosis in rats through poly (ADP-ribose) polymerase activity and Jun N-terminal kinase/activator protein-1 pathway inhibition

Norihisa Uehara, Katsuaki Miki, Reiko Tsukamoto, Yoichiro Matsuoka, Airo Tsubura

Research output: Contribution to journalArticlepeer-review

39 Citations (Scopus)

Abstract

Nicotinamide (NAM) blocks N-methyl-N-nitrosourea (MNU)-induced photoreceptor cell apoptosis in rats, though the underlying molecular mechanisms remain unclear. Activation of the nuclear enzyme poly (ADP-ribose) polymerase (PARP) in response to DNA damage plays a pivotal role in apoptosis. Thus, the role of NAM in the regulation of PARP and Jun N-terminal kinase (JNK)/activator protein-1 (AP-1) was investigated by Western blot analyses. During 7 days after the intraperitoneal injection of MNU (60 mg/kg), rat retinas exhibited DNA fragmentation characteristic of apoptosis and activation of PARP, phosphorylation of JNK and c-Jun, induction of AP-1 (c-Jun and c-Fos) and Bax, as well as photoreceptor cell loss. However, when NAM (1000 mg/kg, subcutaneously) was given immediately after MNU, it was found that PARP activation was diminished, the phosphorylation of JNK and c-Jun was suppressed, and the induction of c-Jun, c-Fos and Bax was suppressed. This resulted in the retinal structure being protected. Therefore, NAM blocked MNU-induced photoreceptor cell apoptosis by inhibiting both PARP activity and the JNK/AP-1 signalling pathway.

Original languageEnglish
Pages (from-to)488-495
Number of pages8
JournalExperimental Eye Research
Volume82
Issue number3
DOIs
Publication statusPublished - Mar 2006
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Ophthalmology
  • Sensory Systems
  • Cellular and Molecular Neuroscience

Fingerprint Dive into the research topics of 'Nicotinamide blocks N-methyl-N-nitrosourea-induced photoreceptor cell apoptosis in rats through poly (ADP-ribose) polymerase activity and Jun N-terminal kinase/activator protein-1 pathway inhibition'. Together they form a unique fingerprint.

Cite this