Growth factors prevent changes in Bcl-2 and Bax expression and neuronal apoptosis induced by nitric oxide

Tamatani, Michio; Ogawa, Satoshi; Núñez, Gabriel; Tohyama, Masaya

doi:10.1038/sj.cdd.4400439

Cited by 115 publications

(71 citation statements)

References 31 publications

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“…The result of such inhibition would be downregulation of survival factors under the control of this transcription factor, such as the antiapoptotic Bcl-2 family members. Indeed, this has been observed by a number of studies, as exogenous NO downregulates Bcl-2 but upregulates the proapoptotic protein, Bax, in neurons, 128,129 and upregulates Bad and Bax, but downregulates Bcl-2 in human colon adenocarcinoma cells. 130 In nonsmall cell lung cancer cells, it has been shown that NF-kB inhibition leads to apoptosis by increasing mitochondrial permeability, thus allowing release of cytochrome c and subsequent caspase activation (see Figure 2).…”

Section: Proapoptotic Mechanismsmentioning

confidence: 96%

Nitric oxide: a key regulator of myeloid inflammatory cell apoptosis

et al. 2003

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Apoptosis of inflammatory cells is a critical event in the resolution of inflammation, as failure to undergo this form of cell death leads to increased tissue damage and exacerbation of the inflammatory response. Many factors are able to influence the rate of apoptosis in neutrophils, eosinophils, monocytes and macrophages. Among these is the signalling molecule nitric oxide (NO), which possesses both anti-and proapoptotic properties, depending on the concentration and flux of NO, and also the source from which NO is derived. This review summarises the differential effects of NO on inflammatory cell apoptosis and outlines potential mechanisms that have been proposed to explain such actions.

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Section: Proapoptotic Mechanismsmentioning

confidence: 96%

Nitric oxide: a key regulator of myeloid inflammatory cell apoptosis

et al. 2003

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“…Harlan Sprague Dawley rat embryos, as described previously (18,19). Briefly, fetal hippocampi were dissected and digested with 0.25% trypsin for 20 min at room temperature in calcium/magnesium-free Hanks' balanced salt solution (Life Technologies, Inc.).…”

Section: Methodsmentioning

confidence: 99%

Akt Activation Protects Hippocampal Neurons from Apoptosis by Inhibiting Transcriptional Activity of p53

Yamaguchi¹,

Tamatani²,

Matsuzaki³

et al. 2001

Journal of Biological Chemistry

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223

143

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Survival factors suppress apoptosis by activating the serine/threonine kinase Akt. To investigate the molecular mechanism underlying activated Akt's ability to protect neurons from hypoxia or nitric oxide (NO) toxicity, we focused on the apoptosis-related functions of p53 and caspases. We eliminated p53 by employing p53-deficient neurons and increased p53 by infection with recombinant adenovirus capable of transducing p53 expression, and we now show that p53 is implicated in the apoptosis induced by hypoxia or NO treatments of primary cultured hippocampal neurons. Although hypoxia and NO induced p53, treatment with insulin-like growth factor-1 significantly inhibited caspase-3-like activation, neuronal death and transcriptional activity of p53. These insulin-like growth factor-1 effects are prevented by wortmannin, a phosphatidylinositol 3-kinase inhibitor. Adenovirus-mediated expression of activated-Akt kinase suppressed p53-dependent transcriptional activation of responsive genes such as Bax, suppressed caspase-3-like protease activity and suppressed neuronal cell death with no effect on the cellular accumulation and nuclear translocation of p53. In contrast, overexpression of kinase-defective Akt failed to suppress these same activities. These results suggest a mechanism where Akt kinase activation reduces p53's transcriptional activity that ultimately rescues neurons from hypoxia-or NO-mediated cell death.

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“…Perlman et al 20 reported that a cell with a high Bax/Bcl-2 ratio was more sensitive to a given apoptotic stimuli when compared with a similar cell type with a comparatively low Bax/Bcl-2 ratio. Tamatani et al 21 hypothesized that the balance between expression of Bax and Bcl-2 proteins determined cell survival or death after an apoptotic stimulus. Therefore an increased Bax/Bcl-2 ratio is a possible indicator of PDT-induced apoptosis in LLC-IL-6 cells.…”

Section: Npe6-mediated Pdt Induced Bax Protein In Llc-il-6 Cellsmentioning

confidence: 99%

Increased cytotoxic effects of photodynamic therapy in IL-6 gene transfected cells via enhanced apoptosis

Usuda¹,

Okunaka²,

Furukawa³

et al. 2001

Int. J. Cancer

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PDT has been reported to induce cancer cell expression of cytokines, such as IL-6 and TNF-␣, but it has been unclear whether cytokine expression by cancer cells is directly related to the antitumor effect of PDT. We treated Lewis lung carcinoma (LLC) cells with a new photosensitizer, mono-Laspartyl chlorin e6 (NPe6) and light from a diode laser and found that expression of the mRNA of IL-2, IL-6, and TNF-␣ was increased by NPe6-mediated-PDT 6 hr later. To elucidate the mechanism of the direct anti-tumor effect of cytokine expression, we examined the photosensitivity of cytokine- To enhance the potential of PDT and to extend its clinical applications, a second generation of photosensitizers is now being assessed, and it is important to elucidate their mechanism of action in PDT. Mono-L-aspartyl chlorin e6 (NPe6) is a water-soluble substance, and NPe6-mediated-PDT has been shown to have an antitumor effect in several experimental models and is currently undergoing clinical evaluation in Japan.Granville et al. 3 reported that PDT induces apoptosis in various tumor cell lines. PDT also induces nonspecific and specific immune responses against tumors in vitro and in vivo. Krosl et al. 4 reported that the antitumor efficacy of PDT is improved by the administration of macrophage activating factors such as granulocyte-macrophage colony activating factor (GM-CSF), whereas Gollnick et al. 5 demonstrated that PDT alters expression of IL-6 and IL-10 in vivo. The immune mechanisms of PDT have never been clarified, however, and it is unknown whether cytokine expression is involved in the antitumor effects of PDT. To elucidate the immune response and the mechanisms of action involved in NPe6-mediated PDT, we examined the effects of cytokine overexpression on PDT by using cytokine gene transfected cells and we have characterized the apoptotic mechanism. MATERIAL AND METHODS Laser light delivery systemA new high-power red laser diode system (Matsushita Industrial Equipment Co., Osaka, Japan), with potential for use in photodynamic therapy (PDT) with NPe6, was employed. This system has a power output of 10 -500 mW/cm 2 at the fiber tip. The irradiation mode is continuous wave (CW), and the delivered energy can be adjusted from 1-1,000 J/cm.2 . 2 Although it runs on 100 V current, the system is 49 ϫ 20 ϫ 40 cm in size, weighs 20 kg, and is easy to take into a sickroom. The power of the laser is easily adjusted, the wavelength of the light is stable (within 0.2 nm), and it is delivered through a quartz fiber. The full width at half maximum is less than 2 nm, which enables uniform, high-density photoradiation, and the power density distribution of the laser, analyzed by a charge-coupled device (CCD) camera, is uniform throughout the photoradiated field. In our study, the diode laser wavelength was adjusted to 664 nm to match the absorption bands of NPe6. PHOTOSENSITIZERCompound NPe6 is an effective photosensitizer that possesses properties such as chemical purity and a major absorption band at 664 nm, features that are potentiall...

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Growth factors prevent changes in Bcl-2 and Bax expression and neuronal apoptosis induced by nitric oxide

Cited by 115 publications

References 31 publications

Nitric oxide: a key regulator of myeloid inflammatory cell apoptosis

Nitric oxide: a key regulator of myeloid inflammatory cell apoptosis

Akt Activation Protects Hippocampal Neurons from Apoptosis by Inhibiting Transcriptional Activity of p53

Increased cytotoxic effects of photodynamic therapy in IL-6 gene transfected cells via enhanced apoptosis

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