Mutations in apoptosis genes: a pathogenetic factor for human disease

Müllauer, Leonhard; Gruber, Petra; Sebinger, David; Buch, Judith; Wohlfart, Sabine; Chott, Andreas

doi:10.1016/s1383-5742(01)00057-6

Cited by 155 publications

(100 citation statements)

References 170 publications

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“…Hence, Bcl-2 return in response to irradiation, after an initial nadir at 1 week, appeared to follow but to lag behind that of PTHrP. Although Bax expression did not appear consistently increased after irradiation, the relative increase in the Bax to Bcl-2 ratio for the first 2-3 weeks after irradiation at this dose in the Sprague-Dawley rat may favor apoptosis (Oltvai et al 1993;Mullauer et al 2001). IHC alone is probably not sensitive enough to demonstrate the subtle differences in the Bcl-2 and Bax that regulate apoptosis, and many other pro-apoptotic and anti-apoptotic molecules are involved in this intricate balance that were not examined at all.…”

Section: Discussionmentioning

confidence: 95%

Temporal Changes in PTHrP, Bcl-2, Bax, Caspase, TGF-β, and FGF-2 Expression Following Growth Plate Irradiation With or Without Radioprotectant

Damron

Mathur

Horton

et al. 2004

J Histochem Cytochem.

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S U M M A R YThis study examined temporal changes in growth plate apoptosis molecules and growth factors in an animal model of radiation injury with and without a radioprotectant. Thirty weanling 5-week Sprague-Dawley rats underwent right knee irradiation with single-fraction 17.5 Gy while the left served as internal control. Six animals each were sacrificed at 0.5, 1, 2, 3, or 4 weeks after irradiation. Half of the animals received pretreatment with amifostine (WR-2721) radioprotectant. Immunohistochemical staining for PTHrP, Bcl-2, Bax, caspase-3, FGF-2, and TGF-␤ was performed. PTHrP decreased to a nadir at 1 week after irradiation but rebounded to above control levels at 2 weeks in the reserve and transitional zones. The radioprotectant amifostine blunted the decrease in PTHrP but kept PTHrP expression lower than controls during the rebound phase in untreated irradiated animals. Hypertrophic zone Bax expression was decreased by amifostine in both irradiated and non-irradiated limbs at 1 and 2 weeks. FGF, TGF-␤ , Bcl-2, and caspase levels generally decreased at 1 week and returned thereafter toward control levels. These findings underscore the importance of PTHrP in response to growth plate irradiation and show the novel finding of a decrease in Bax expression with amifostine pretreatment.

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Section: Discussionmentioning

confidence: 95%

Temporal Changes in PTHrP, Bcl-2, Bax, Caspase, TGF-β, and FGF-2 Expression Following Growth Plate Irradiation With or Without Radioprotectant

Damron

Mathur

Horton

et al. 2004

J Histochem Cytochem.

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“…UV-induced apoptosis depends upon the mitochondrial pathway, where p53 plays a leading role by either up-regulating apoptosis-promoting genes such as Bax and Fas/Apo-1 or down-regulating expression of BCL-2-suppressing genes [25][26][27][28].…”

Section: Introduction Introduction Introduction Introductionmentioning

confidence: 99%

Effects of UV wavelength on cell damages caused by UV irradiation in PC12 cells

Masuma

Kashima

Kurasaki

et al. 2013

Journal of Photochemistry and Photobiology B: Biology

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Ultraviolet (UV) radiations present in sunlight are a major etiologic factor for many skin diseases and induce DNA damage through formation of cyclobutane pyrimidine dimer (CPD). This study was conducted to determine the toxicological effects of different wavelengths (250, 270, 290, and 310 nm) and doses of UV radiation on cell viability, DNA structure, and DNA damage repair mechanisms in a PC12 cell system. For this, we evaluated cell viability and CPD formation. Cell survival rate was markedly decreased 24 h after UV irradiation in a dose-dependent manner at all wavelengths (except at 310 nm). Cell viability increased with increasing wavelength in the following order: 250 < 270 < 290 < 310 nm. UV radiation at 250 nm showed the highest cell killing ability, with a median lethal dose (LD50) of 120 mJ/cm2. The LD50 gradually increased with increase in wavelength. Among the 4 wavelengths tested, the highest LD50 (6000 mJ/cm2) was obtained for 310 nm. CPD formation decreased substantially with increasing wavelength. Among the 4 wavelengths, the proportion of CPD formation was highest at 250 nm and lowest at 310 nm. On the basis of LD50 values for each wavelength, PC12 cells irradiated with UV radiation of 290 nm showed maximum DNA repair ability, whereas those irradiated with the 310-nm radiation did not show any repair ability. Toxicity of UV radiation varied with wavelengths and exposure doses

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“…It has been suggested that malfunction or deregulation of this process may be important in the establishment or development of a number of diseases, including neurodegenerative disorders and cancer (4,5).…”

Section: Introductionmentioning

confidence: 99%

Differential targeting of protein kinase B in cell death induced by sulindac and its metabolite sulindac sulfide

Marotta

Parhar²,

Hundal³

et al. 2006

Int J Oncol

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Abstract. Non-steroidal anti-inflammatory drugs such as sulindac inhibit human colorectal carcinogenesis through a mechanism involving the direct inhibition of cyclooxygenase (Cox)-2. However, a wealth of recent evidence indicates that these agents might elicit their effects through mechanisms independently of Cox-2. In this study, we investigated the effects of sulindac and its metabolite, sulindac sulfide on modulation of the critical survival kinase, protein kinase B (PKB). Here, we demonstrate for the first time that treatment with either sulindac or sulindac sulfide results in a decrease in PKB activity, and we provide compelling evidence that this occurs through two distinct mechanisms. Additionally, we report that overexpression of, and conditional activation of PKB attenuates the apoptotic effects of sulindac, but not for sulindac sulfide -the metabolic metabolite of sulindac. We also demonstrate that treatment with sulindac sulfide, but not sulindac, results in a very early robust activation of both caspase-8 and -9. Furthermore, we show that the apoptotic effects of sulindac sulfide can be reverted by both the caspase-8 and -9 inhibitors. Evidence is provided to indicate that PKB is targeted by robust caspase activation due to sulindac sulfide. Hence, further investigation into the mechanisms regulating conversion of sulindac to sulindac sulfide (or direct use of the latter compound), may enhance our ability to target cancers with enhanced signaling through the growth factor➝phosphatidylinositol 3-kinase pathway.

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Mutations in apoptosis genes: a pathogenetic factor for human disease

Cited by 155 publications

References 170 publications

Temporal Changes in PTHrP, Bcl-2, Bax, Caspase, TGF-β, and FGF-2 Expression Following Growth Plate Irradiation With or Without Radioprotectant

Temporal Changes in PTHrP, Bcl-2, Bax, Caspase, TGF-β, and FGF-2 Expression Following Growth Plate Irradiation With or Without Radioprotectant

Effects of UV wavelength on cell damages caused by UV irradiation in PC12 cells

Differential targeting of protein kinase B in cell death induced by sulindac and its metabolite sulindac sulfide

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