Clitocybins, novel isoindolinone free radical scavengers, from mushroom Clitocybe aurantiaca inhibit apoptotic cell death and cellular senescence.
High concentration of intracellular reactive oxygen species (ROS) plays a role in damaging biological systems. We isolated clitocybin A from the culture broth of Clitocybe aurantiaca and then clitocybin B and C derivatives were synthesized from clitocybin A. IMR-90 lung fibroblast cells were pre-treated or post-treated with clitocybin A, B and C to the addition of 100 muM H(2)O(2). These compounds inhibited the level of intracellular reactive oxygen species (ROS) and H(2)O(2)-induced cell death as judged by hypodiploid cell formation. The inhibitory effect of clitocybins on H(2)O(2)-induced cell death was comparable to that with N-acetylcysteine (NAC), a well-known ROS scavenger. The inhibition of H(2)O(2)-induced cell death by clitocybins was mediated by the reduction of caspase 3 and 9 activation, cytochrome c release from mitochondria and the degradation of IkappaB-alpha and IkappaB-beta, which could be resulted in the prevention of cellular senescence. It suggests that clitocybins are novel compounds scavenging ROS and protect cells from apoptosis and cellular senescence.
Department of Bioscience and Biotechnology, Sejong University, 98 Kunja-Dong Kwangjin-Gu, Seoul 143-747, Republic of Korea. eunyimoon@sejong.ac.kr
Eun-Yi
EY
Moon
Jin-Mi
JM
Oh
Young-Hee
YH
Kim
In-Ja
IJ
Ryoo
Ick-Dong
ID
Yoo
D000111:Acetylcysteine / Q000494:pharmacology; D000363:Agaricales; D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3 / Q000378:metabolism; D053453:Caspase 9 / Q000378:metabolism; D002460:Cell Line; D016922:Cellular Senescence / Q000187:drug effects*; D045304:Cytochromes c / Q000378:metabolism; D016166:Free Radical Scavengers / Q000138:chemical synthesis / Q000494:pharmacology*; D005656:Fungal Proteins / Q000138:chemical synthesis / Q000494:pharmacology*; D006801:Humans; D006861:Hydrogen Peroxide; D020672:I-kappa B Proteins / Q000378:metabolism; D054833:Isoindoles / Q000138:chemical synthesis / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D008928:Mitochondria / Q000378:metabolism; D000072000:NF-KappaB Inhibitor alpha
D016166:Free Radical Scavengers; D005656:Fungal Proteins; C083487:I kappa B beta protein; D020672:I-kappa B Proteins; D054833:Isoindoles; C000606204:NFKBIA protein, human; C535086:clitocybin A; D000072000:NF-KappaB Inhibitor alpha; C546683:clitocybin C; D045304:Cytochromes c; D006861:Hydrogen Peroxide; C546682:clitocybin B; D053148:Caspase 3; D053453:Caspase 9; D000111:Acetylcysteine