Expression of V642 APP mutant causes cellular apoptosis as Alzheimer trait-linked phenotype.

Yamatsuji, Tomoki; Okamoto, Takashi; Takeda, Shuji; Murayama, Yoshitake; Tanaka, N; Nishimoto, Ikuo

doi:10.1002/j.1460-2075.1996.tb00382.x

Cited by 109 publications

(107 citation statements)

References 59 publications

(92 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…7 shows that transfection with the vector alone induced little or no DNA fragmentation after 36 h. In contrast, transfection with the caveolin-1 cDNA resulted in marked nucleosomal DNA fragmentation. As we previously described, transfection with another transmembrane protein (normal Alzheimer's precursor protein) failed to induce nucleosomal fragmentation within the same assay system (41,42). Thus, it appears that recombinant expression of caveolin-1 is sufficient to induce nucleosomal DNA fragmentation, a classic hallmark of apoptotic cell death.…”

Section: Caveolin-1 Expression Inhibits Ras-mediated Transcriptional mentioning

confidence: 54%

“…Apoptosis-The TUNEL assay was performed with a kit distributed by Oncor, as described previously (41,42). Briefly, F11 cells or COS-7 cells (ϳ4 ϫ 10 4 cells/well) were seeded onto glass coverslips with in a 24-well dish.…”

Section: Methodsmentioning

confidence: 99%

“…To evaluate this possibility, we employed an established assay system to detect apoptotic cell death (41,42). The caveolin-1 cDNA (pCB-7-Cav-1) or vector alone (pCB-7) were transiently expressed in F11 cells.…”

Section: Caveolin-1 Expression Inhibits Ras-mediated Transcriptional mentioning

confidence: 99%

“…The caveolin-1 cDNA (pCB-7-Cav-1) or vector alone (pCB-7) were transiently expressed in F11 cells. Nucleosomal DNA fragmentation in these cells was directly assessed by the TUNEL assay (terminal deoxynucleotidyltransferase-mediated deoxyuridine triphosphate (dUTP) nick-end labeling) (41,42). Fig.…”

Section: Caveolin-1 Expression Inhibits Ras-mediated Transcriptional mentioning

confidence: 99%

See 3 more Smart Citations

Recombinant Expression of Caveolin-1 in Oncogenically Transformed Cells Abrogates Anchorage-independent Growth

Engelman¹,

Wykoff²,

Yasuhara³

et al. 1997

Journal of Biological Chemistry

345

336

View full text Add to dashboard Cite

Caveolae are plasma membrane-attached vesicular organelles. Caveolin-1, a 21-24-kDa integral membrane protein, is a principal component of caveolae membranes in vivo. Both caveolae and caveolin are most abundantly expressed in terminally differentiated cells: adipocytes, endothelial cells, and muscle cells. Conversely, caveolin-1 mRNA and protein expression are lost or reduced during cell transformation by activated oncogenes such as v-abl and H-ras (G12V); caveolae are absent from these cell lines. However, its remains unknown whether down-regulation of caveolin-1 protein and caveolae organelles contributes to their transformed phenotype.Here, we have expressed caveolin-1 in oncogenically transformed cells under the control of an inducible-expression system. Regulated induction of caveolin-1 expression was monitored by Western blot analysis and immunofluorescence microscopy. Our results indicate that caveolin-1 protein is expressed well using this system and correctly localizes to the plasma membrane. Induction of caveolin-1 expression in v-Abl-transformed and H-Ras (G12V)-transformed NIH 3T3 cells abrogated the anchorage-independent growth of these cells in soft agar and resulted in the de novo formation of caveolae as seen by transmission electron microscopy. Consistent with its antagonism of Ras-mediated cell transformation, caveolin-1 expression dramatically inhibited both Ras/MAPK-mediated and basal transcriptional activation of a mitogen-sensitive promoter. Using an established system to detect apoptotic cell death, it appears that the effects of caveolin-1 may, in part, be attributed to its ability to initiate apoptosis in rapidly dividing cells. In addition, we find that caveolin-1 expression levels are reversibly down-regulated by two distinct oncogenic stimuli. Taken together, our results indicate that down-regulation of caveolin-1 expression and caveolae organelles may be critical to maintaining the transformed phenotype in certain cell populations.

show abstract

Section: Caveolin-1 Expression Inhibits Ras-mediated Transcriptional mentioning

confidence: 54%

Section: Methodsmentioning

confidence: 99%

Section: Caveolin-1 Expression Inhibits Ras-mediated Transcriptional mentioning

confidence: 99%

Section: Caveolin-1 Expression Inhibits Ras-mediated Transcriptional mentioning

confidence: 99%

See 2 more Smart Citations

Recombinant Expression of Caveolin-1 in Oncogenically Transformed Cells Abrogates Anchorage-independent Growth

Engelman¹,

Wykoff²,

Yasuhara³

et al. 1997

Journal of Biological Chemistry

345

336

View full text Add to dashboard Cite

show abstract

“…The accumulation of A␤-amyloid in brains with AD may be important in this regard because increased levels of Bax and p53 immunoreactivity have been localized within and around A␤-amyloid deposits in senile plaques (de la Monte et al, , 1998Su et al, 1997;Tortosa et al, 1998). Experimentally, A␤-amyloid has been shown to be neurotoxic or to induce proapoptosis and inhibit cell survival gene expression (Davis et al, 1999;Forloni et al, 1996;Giambarella et al, 1997;Gunn-Moore and Tavare, 1998;Ivins et al, 1999;Paradis et al, 1996;Prehn et al, 1996;Sayre et al, 1997a;Yamatsuji et al, 1996) and activate oxidative stress-related genes (Pappolla et al, 1998). Moreover, A␤-amyloid-induced cellular degeneration can be rescued or prevented by treatment with antioxidant or free-radical scavenger agents (Prehn et al, 1996).…”

Section: Figurementioning

confidence: 99%

Mitochondrial DNA Damage as a Mechanism of Cell Loss in Alzheimer's Disease

Monte

Luong

Neely

et al. 2000

Laboratory Investigation

206

125

View full text Add to dashboard Cite

SUMMARY:Aging is associated with impaired mitochondrial function caused by accumulation of oxygen free radical-induced mitochondrial (Mt) DNA mutations. One prevailing theory is that age-associated diseases, including Alzheimer's disease (AD), may be precipitated, propagated, or caused by impaired mitochondrial function. To investigate the role of MtDNA relative to genomic (Gn) DNA damage in AD, temporal lobe samples from postmortem AD (n ϭ 37) and control (n ϭ 25) brains were analyzed for MtDNA and GnDNA fragmentation, mitochondrial protein and cytochrome oxidase expression, MitoTracker Green fluorescence (to assess mitochondrial mass/abundance), and 8-oxo-7,8-dihydro-2Ј-deoxyguanosine (8-OHdG) immunoreactivity. Brains with AD had more extensive nicking and fragmentation of both MtDNA and GnDNA as demonstrated by agarose gel electrophoresis, end-labeling, and the in situ terminal deoxynucleotide transferase end-labeling (TUNEL) assay, and only the brains with AD had detectable 8-OHdG immunoreactivity in cortical neurons. Increased MtDNA damage in AD was associated with reduced MtDNA content, as demonstrated by semiquantitative PCR analysis and reduced levels of Mt protein and cytochrome oxidase expression by Western blot analysis or immunohistochemical staining with image analysis. The finding of reduced MitoTracker Green fluorescence in AD brains provided additional evidence that reduced Mt mass/abundance occurs with AD neurodegeneration. The presence of increased MtDNA and GnDNA damage in AD suggest dual cell death cascades in AD. Impaired mitochondrial function caused by MtDNA damage may render brain cells in AD more susceptible to oxidative injury and thereby provide a mechanism by which systemic or environmental factors could influence the course of disease. (Lab Invest 2000, 80:1323-1335.

show abstract

Bcl-xl-Specific antibody labels activated microglia associated with Alzheimer's disease and other pathological states

Drache

Diehl

Beyreuther³

et al. 1997

J. Neurosci. Res.

View full text Add to dashboard Cite

Expression of V642 APP mutant causes cellular apoptosis as Alzheimer trait-linked phenotype.

Cited by 109 publications

References 59 publications

Recombinant Expression of Caveolin-1 in Oncogenically Transformed Cells Abrogates Anchorage-independent Growth

Recombinant Expression of Caveolin-1 in Oncogenically Transformed Cells Abrogates Anchorage-independent Growth

Mitochondrial DNA Damage as a Mechanism of Cell Loss in Alzheimer's Disease

Bcl-xl-Specific antibody labels activated microglia associated with Alzheimer's disease and other pathological states

Contact Info

Product

Resources

About