4-NQO induces apoptosis via p53-dependent mitochondrial signaling pathway

Han, Hongbing; Qiu-zhen, Pan; Zhang, Baolu; Li, Jia; Deng, Xuemei; Lian, Zhengxing; Li, Ning

doi:10.1016/j.tox.2006.11.045

Cited by 26 publications

(19 citation statements)

References 43 publications

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“…Caspase‐3 and ‐9 activities were measured by caspase‐3/‐9 colorimetric assay kit (Nanjing Keygen Biotech) according to previous description (Han et al. 2007).…”

Section: Methodsmentioning

confidence: 99%

Myofibroblasts protect myoblasts from intrinsic apoptosis associated with differentiation via β1 integrin‐PI3K/Akt pathway

Zhang

Lian

et al. 2010

Dev Growth Differ

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Skeletal myoblasts withdrawing from cell cycle is a prerequisite for myodifferentiation, while upon proliferation ⁄ differentiation transformation, a large portion of myoblasts will undergo apoptosis. Skeletal fibroblasts, residing in muscle tissue both during and post myogenesis, have been proofed to play pivotal roles in muscle development, while their effect on myoblast apoptosis being coincident with differentiation has not been reported. Using a membrane insert co-culture system, we studied it and found that the mitochondrial pathway played a crucial role in myoblast apoptosis during differentiation, and fibroblasts promoted not only cell cycle withdrawal but also myoblast survival in a paracrine fashion, which was coupled with upregulations of b1 integrin, phosphorylated Akt and anti-apoptotic protein Bcl2. To determine the effect of b1 integrin in the process, we transfected myoblasts with siRNA specific for b1 integrin before co-culture and found that b1 integrin knockdown abolished anti-apoptotic ability of myoblasts and inhibited Akt activation and Bcl2 expression. Blockage of PI3K ⁄ Akt pathway with wortmannin also seriously impaired the protective effect of fibroblasts on myoblasts and fibroblast-induced Bcl2 expression. The data demonstrated that fibroblasts protected myoblasts from intrinsic apoptosis associated with differentiation, and b1 integrin-PI3K ⁄ Akt pathway activation was required for the process.

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“…Caspase‐3 and ‐9 activities were measured by caspase‐3/‐9 colorimetric assay kit (Nanjing Keygen Biotech) according to previous description (Han et al. 2007).…”

Section: Methodsmentioning

confidence: 99%

Myofibroblasts protect myoblasts from intrinsic apoptosis associated with differentiation via β1 integrin‐PI3K/Akt pathway

Zhang

Lian

et al. 2010

Dev Growth Differ

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“…4-NQO is a potent mutagen, and during its metabolism, DNA adducts occur through interaction between DNA and 4-NQO intermediate, 4-hydroxyaminoquinoline 1-oxide (Ac-4-HAQO) [13]. As a consequence, the helical structure of DNA changes which results in micronuclei/chromosomal breakage [14].…”

Section: Discussionmentioning

confidence: 99%

“…Due to mutagenic stress, cells undergo apoptosis in the case of DNA damage being beyond repair. Moreover, 4-NQO can induce apoptosis by the p53-dependent mitochondrial signaling pathway [13]. Recently, we reported protective effects of sesame oil on 4-NQO-induced DNA damage in mice [16].…”

Section: Discussionmentioning

confidence: 99%

Antimutagenic and Antiapoptotic Effects of Aqueous Root Extract of Inula racemosa Hook. f. on 4-NQO-Induced Genetic Damage in Mice

Arumugam

Murugan

2013

ISRN Pharmacology

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The present study was performed as part of an attempt to authenticate the use of Inula racemosa root extract as traditional medicine in India by experimentally investigating their protective effects on 4-nitroquinoline-1-oxide (4-NQO) induced DNA damage and apoptosis in mice bone marrow cells. Aqueous root extract (ARE) of Inula racemosa (100, 200 and 400 mg/kg bw) with and without 4-NQO along with vehicle control (H2O) were administered orally for five consecutive days. 4-NQO (7.5 mg/kg bw) was injected intraperitoneally to the mice on the sixth day. After 24 h, the animals were sacrificed and extracted bone marrow cells were used for micronuclei and apoptotic analysis. Antiapoptotic effect of ARE (400 mg/kg bw) was measured by the use of Annexin V-FITC assay kit. 4-NQO generated the frequency of micronucleated polychromatic erythrocytes (MnPCEs) by about 4.7 times the control value, 14.29 MnPCEs/2500 PCEs. Pretreatment with ARE significantly reduced the MnPCEs frequency (39–72%) with respect to their doses, and increased PCEs/NCEs ratio was observed over the 4-NQO alone. 4-NQO-induced total apoptotic cells were about 12% over the control which was significantly (P < 0.05) brought down to 3.5% by pretreatment with 400 mg/kg bw of ARE. This was the first report that recorded the protective effects of I. racemosa on 4-NQO-induced DNA damage and apoptosis in mice bone marrow cells.

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“…4-NQO is a potent mutagen that exerts its genotoxicity in two ways. In the first and during metabolism, 4-NQO is converted into 4-hydroxyaminoquinoline 1-oxide (Ac-4-HAQO) and interacts with DNA at N2 and C8 of guanosine and also at N6 of adenine forming adducts (Han et al , 2007). As a consequence, the helical structure of DNA changes, resulting in micronuclei/chromosomal breakage (Diekmann et al , 2004).…”

Section: Discussionmentioning

confidence: 99%

“…During genotoxic stress, cells undergo apoptosis in the case of DNA damage being beyond repair. 4-NQO can induce apoptosis by way of the p53-dependent mitochondrial signaling pathway (Han et al , 2007). The results clearly indicated that MnPCEs induced by 4-NQO (~4 times higher than control - Table 3) was reflected in the form of total apoptotic cells (~4 times higher than control value; Figure 2).…”

Section: Discussionmentioning

confidence: 99%

Protective effects of solvent fractions of Mentha spicata (L.) leaves evaluated on 4-nitroquinoline-1-oxide induced chromosome damage and apoptosis in mouse bone marrow cells

Arumugam

Ramesh

2009

Genet. Mol. Biol.

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Spearmint leaves (Mentha spicata L.) contain high levels of antioxidants that are known to protect against both exogenous and endogenous DNA damage. In this study, the protective effects of the hexane fraction (HF), chloroform fraction (CF) and ethyl acetate fraction (EAF) in an ethanol extract from M. spicata were evaluated against 4-nitroquinoline-1-oxide (4-NQO) induced chromosome damage and apoptosis in bone marrow cells of Swiss albino mice. Two (EAF; 80 and 160 mg/ kg body weight -bw) or three (HF and CF; 80, 160 and 320 mg/ kg bw) doses of solvent fractions or vehicle control (25% DMSO in water) were administered orally for five consecutive days. Upon the sixth day, 4-NQO was injected intraperitoneally. The animals were killed the following day. Other control groups were comprised of animals treated with either the vehicle control or the various doses of solvent fractions, but with no 4-NQO treatment. 4-NQO induced micro-nucleated polychromatic erythrocytes (MnPCEs) in all the test groups. However, pre-treatment of animals with the solvent fractions significantly reduced the 4-NQO-induced MnPCEs as well as the percentage of apoptotic cells. The reduction of both MnPCE and apoptosis was more evident following the pre-treatment of animals with 160 mg/kg bw EAF.

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4-NQO induces apoptosis via p53-dependent mitochondrial signaling pathway

Cited by 26 publications

References 43 publications

Myofibroblasts protect myoblasts from intrinsic apoptosis associated with differentiation via β1 integrin‐PI3K/Akt pathway

Myofibroblasts protect myoblasts from intrinsic apoptosis associated with differentiation via β1 integrin‐PI3K/Akt pathway

Antimutagenic and Antiapoptotic Effects of Aqueous Root Extract of Inula racemosa Hook. f. on 4-NQO-Induced Genetic Damage in Mice

Protective effects of solvent fractions of Mentha spicata (L.) leaves evaluated on 4-nitroquinoline-1-oxide induced chromosome damage and apoptosis in mouse bone marrow cells

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