Estrogen Regulates Bcl-w and Bim Expression: Role in Protection against β-Amyloid Peptide-Induced Neuronal Death

Yao, Meicun; Nguyen, Thuy‐Vi V.; Pike, Christian J.

doi:10.1523/jneurosci.2382-06.2007

Cited by 111 publications

(90 citation statements)

References 84 publications

(93 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…In addition, bFGF, but not NGF decreased Ca++ disturbances in hippocampal neurons [26]. Estrogen alters expression of Bcl proteins involved in apoptosis pathways [41].…”

Section: Discussionmentioning

confidence: 93%

Beta-amyloid toxicity and reversal in embryonic rat septal neurons

Jarvis

Assis-Nascimento

Mudd

et al. 2007

Neuroscience Letters

View full text Add to dashboard Cite

show abstract

“…In addition, bFGF, but not NGF decreased Ca++ disturbances in hippocampal neurons [26]. Estrogen alters expression of Bcl proteins involved in apoptosis pathways [41].…”

Section: Discussionmentioning

confidence: 93%

Beta-amyloid toxicity and reversal in embryonic rat septal neurons

Jarvis

Assis-Nascimento

Mudd

et al. 2007

Neuroscience Letters

View full text Add to dashboard Cite

show abstract

“…Among the BH3-only proteins, Bim plays a critical role in a variety of neuronal death paradigms, including cerebellar granule neurons (CGNs) deprived of activity (Putcha et al, 2001;Shi et al, 2005), sympathetic neurons during removal of nerve growth factor (NGF) (Whitfield et al, 2001), and cortical neurons exposed to ␤-amyloid peptide (Biswas et al, 2007b;Yao et al, 2007). For example, CGNs and sympathetic neurons from Bim knock-out mice display a significant delay in apoptosis (Putcha et al, 2001;Coultas et al, 2007), demonstrating that Bim is a critical mediator of a proapoptotic signaling pathway in these neurons.…”

Section: Introductionmentioning

confidence: 99%

Egr-1 TransactivatesBimGene Expression to Promote Neuronal Apoptosis

Xie¹,

Wang²,

Zheng³

et al. 2011

J. Neurosci.

View full text Add to dashboard Cite

The proapoptotic BH3-only protein Bim is a crucial regulator of neuronal apoptosis. Previous studies have indicated the involvement of the c-Jun, FOXO1/3a, and B/C-Myb transcription factors in the regulation of Bim during neuronal apoptosis. However, the mechanism underlying the transcriptional regulation of Bim in activity deprivation-induced neuronal apoptosis has remained unclear. The present study demonstrates that early growth response 1 (Egr-1), rather than c-Jun, FOXO1/3a, or B/C-Myb, directly transactivates Bim gene expression to mediate apoptosis of rat cerebellar granule neurons. We showed that Egr-1 was sufficient and necessary for neuronal apoptosis. Suppression of Egr-1 activity using dominant-negative mutant or knockdown of Egr-1 using small interfering RNAs led to a decrease in Bim expression, whereas overexpression of Egr-1 resulted in induction of Bim. Deletion and site-directed mutagenesis of the Bim promoter revealed that Bim transcriptional activation depends primarily on a putative Egr-binding sequence between nucleotides Ϫ56 and Ϫ47 upstream of the start site. We also showed that Egr-1 binding to this sequence increased in response to activity deprivation in vitro and in vivo. Moreover, inhibition of Egr-1 binding to the Bim promoter, by mithramycin A and chromomycin A3, reduced the activity deprivation-induced increases in Bim promoter activity and mRNA and protein levels and protected neurons from apoptosis, further supporting the Egr-1-mediated transactivation of Bim. Additionally, Bim overcame the Egr-1 knockdown-mediated inhibition of apoptosis, whereas Bim knockdown impaired the increase in apoptosis induced by Egr-1. These findings establish Bim as an Egr-1 target gene in neurons, uncovering a novel Egr-1/Bim pathway by which activity deprivation induces neuronal apoptosis.

show abstract

“…Interestingly, the present study demonstrated that OVX for 5 weeks increased neuronal ABAD level in the mouse hippocampus. Taken together with recent studies showing that estrogen protects neuronal cells from Aβ-induced apoptosis by regulating the expression of mitochondrial proteins (Yao et al, 2007;Nilsen et al, 2006), it is suggested that estrogen also directly regulates ABAD expression and that the cessation of negative regulation by OVX results in the overexpression of ABAD. On the other hand, it is also demonstrated that ABAD expression is increased in an Aβ-rich environment (Yan et al, 1997;He et al, 2002).…”

Section: Discussionmentioning

confidence: 71%

“…In vitro findings from cultured neurons suggest that estrogen may prevent AD pathogenesis by reducing Aβ generation, protecting against Aβ-mediated neurotoxicity, and enhancing Aβ clearance (Xu et al, 2006;Li et al, 2000). In addition, recent studies indicate that estrogen protects against Aβ-induced neuronal death by maintaining mitochondrial function (Yao et al, 2007;Nilsen et al, 2006). These finding indicate that Aβ and estrogen relate closely and incompatibly regulate Aβ-mediated AD pathology.…”

Section: Introductionmentioning

confidence: 99%

Ovariectomy increases neuronal amyloid-β binding alcohol dehydrogenase level in the mouse hippocampus

Fukuzaki

Takuma

Funatsu

et al. 2008

Neurochemistry International

View full text Add to dashboard Cite

Ovarian hormone decline after menopause may influence cognitive performance and increase the risk for Alzheimer's disease (AD) in women. Amyloid-β peptide (Aβ) has been proposed to be the primary cause of AD. In this study, we examined whether ovariectomy (OVX) could affect the levels of cofactors Aβ-binding alcohol dehydrogenase (ABAD) and receptor for advanced glycation endproducts (RAGE), which have been reported to potentiate Aβ-mediated neuronal perturbation, in mouse hippocampus, correlating with estrogen and Aβ levels. Female ICR mice were randomly divided into ovariectomized or sham-operated groups, and biochemical analyses were carried out at 5 weeks after the operation. OVX for 5 weeks significantly decreased hippocampal 17β-estradiol level, while it tended to reduce the hormone level in serum, compared with the sham-operated control. In contrast, OVX did not affect hippocampal Aβ 1-40 level, although it significantly increased serum Aβ 1-40 level. Furthermore, we demonstrated that OVX increased hippocampal ABAD level in neurons, but not astrocytes, while it did not affect RAGE level. These findings suggest that the expression of neuronal ABAD depends on estrogen level in the hippocampus and the increase in serum Aβ and hippocampal ABAD induced by ovarian hormone decline may be associated with pre-stage of memory deficit in postmenopausal women and Aβ-mediated AD pathology.

show abstract

Estrogen Regulates Bcl-w and Bim Expression: Role in Protection against β-Amyloid Peptide-Induced Neuronal Death

Cited by 111 publications

References 84 publications

Beta-amyloid toxicity and reversal in embryonic rat septal neurons

Beta-amyloid toxicity and reversal in embryonic rat septal neurons

Egr-1 TransactivatesBimGene Expression to Promote Neuronal Apoptosis

Ovariectomy increases neuronal amyloid-β binding alcohol dehydrogenase level in the mouse hippocampus

Contact Info

Product

Resources

About