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Nikki J. Holbrook
National Institutes of Health
125Publications
64H-index
21.3kCitations
Publications 125
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#1Nikki J. HolbrookH-Index: 64
Last.Claudette M. ComeauH-Index: 3
view all 6 authors...
Using a cloned cDNA copy of T-cell growth factor (TCGF) mRNA from the Jurkat leukemic T-cell line, we have isolated three overlapping TCGF genomic clones from a human DNA library. The entire TCGF gene is contained with- in two adjacent EcoRI fragments spanning about 8 kilobases. The complete nucleic acid sequence was determined. The gene is divided into four exons. The 5' untranslated region and the first 49 amino acids of the protein, 20 of which constitute a signal polypeptide and are not pres...
#1Wanli W. SmithH-Index: 3
#2Darrell D. Norton (NIH: National Institutes of Health)H-Index: 8
Last.John W. Kusiak (NIH: National Institutes of Health)H-Index: 21
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Excessive accumulation of amyloid β-peptide (Aβ) plays an early and critical role in synapse and neuronal loss in Alzheimer's Disease (AD). Increased oxidative stress is one of the mechanisms whereby Aβ induces neuronal death. Given the lessened susceptibility to oxidative stress exhibited by mice lacking p66Shc, we investigated the role of p66Shc in Aβ toxicity. Treatment of cells and primary neuronal cultures with Aβ caused apoptotic death and induced p66Shc phosphorylation at Ser36. Ectopic e...
#1Stefan M. Schieke (HHU: University of Düsseldorf)H-Index: 6
#2Claudia von Montfort (HHU: University of Düsseldorf)H-Index: 11
Last.Lars-Oliver Klotz (HHU: University of Düsseldorf)H-Index: 38
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Singlet oxygen, an electronically excited form of molecular oxygen, is a primary mediator of the activation of stress-activated protein kinases elicited by ultraviolet A (UVA; 320–400 nm). Here, the effects of singlet oxygen (1O2) on the extracellular signal-regulated kinase (ERK) 1/2 and Akt/protein kinase B pathways were analyzed in human dermal fibroblasts. While basal ERK 1/2 phosphorylation was lowered in cells exposed to either 1O2, UVA or photodynamic treatment, Akt was moderately activat...
#1Ji Li (Yale University)H-Index: 3
#2Nikki J. Holbrook (Yale University)H-Index: 9
Abstract The endoplasmic reticulum (ER), as a processing plant for the folding and posttranslational modification of proteins, is exquisitely sensitive to changes in its internal environment. Various conditions, collectively termed ‘ER stress’, can perturb ER functions, leading to the activation of a complex response known as the unfolded protein response. Here, we investigated the response of hepatocytes derived from young (4–5 months) and aged (24–26 months) rats to two agents, thapsigargin (T...
#1Ji Li (Yale University)H-Index: 3
#2Nikki J. Holbrook (Yale University)H-Index: 9
Abstract Aging is often characterized by reduced stress tolerance and decreased proliferative capacity, but little is known about the effects of aging on signaling pathways important in regulating these responses. Recent studies from our laboratory have implicated impairments in epidermal growth factor receptor (EGFR) signaling and extracellular signal-regulated kinase (ERK) activation to both effects in rat hepatocytes. Here we investigated the responsiveness of hepatocytes derived from young (...
#1Shizuo Ikeyama (Yale University)H-Index: 1
#2Xian-Tao Wang (Yale University)H-Index: 1
Last.Nikki J. Holbrook (Yale University)H-Index: 9
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Abstract Aging is generally accompanied by reduced tolerance to oxidative stress and altered responsiveness to proliferative signals. We have shown that hepatocytes derived from aged rats (24–26 months) exhibit greater sensitivity to H2O2 treatment and reduced proliferation following epidermal growth factor (EGF) treatment than cells of young adult rats (5–6 months). Here we examined the effects of aging and calorie restriction (CR) on expression of the oxidative stress-inducible and pro-apoptot...
#1Rika van Huizen (Yale University)H-Index: 2
#2Jennifer L. Martindale (Yale University)H-Index: 4
Last.Nikki J. Holbrook (Yale University)H-Index: 9
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Abstract The unfolded protein response, which is activated in response to the loss of endoplasmic reticulum (ER) Ca2+ homeostasis and/or the accumulation of misfolded, unassembled, or aggregated proteins in the ER lumen, involves both transcriptional and translational regulation. In the current studies we sought to identify novel ER stress-induced genes by conducting microarray analysis on tunicamycin-treated cells. We identified P58IPK, an inhibitor of the interferon-induced double-stranded RNA...
The inhibitory effect of caveolin on the cellular response to growth factor stimulation is well established. Given the significant overlap in signaling pathways involved in regulating cell proliferation and stress responsiveness, we hypothesized that caveolin would also affect a cell's ability to respond to environmental stress. Here we investigated the ability of caveolin-1 to modulate the cellular response to sodium arsenite and thereby alter survival of the human cell lines 293 and HeLa. Cell...
#1Shizuo Ikeyama (NIH: National Institutes of Health)H-Index: 3
#2Gertrude C. Kokkonen (NIH: National Institutes of Health)H-Index: 15
Last.Nikki J. Holbrook (Yale University)H-Index: 9
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Abstract It is well established that the proliferative potential of the liver declines with aging. Epidermal growth factor (EGF)-stimulated DNA synthesis is reduced in hepatocytes from aged rats relative to young rats, and this reduction correlates with diminished activation of the extracellular signal-regulated kinase (ERK) pathway and lower phosphorylation of the EGF receptor on residue Y1173. Calorie restriction (CR) can increase rodent life span and retard many age-associated declines in phy...
#1Ollivier MilhavetH-Index: 16
#2Jennifer L. Martindale (NIH: National Institutes of Health)H-Index: 45
Last.Mark P. MattsonH-Index: 177
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Mutations in the presenilin-1 (PS1) gene cause early onset familial Alzheimer's disease (FAD) by a mechanism believed to involve perturbed endoplasmic reticulum (ER) function and altered proteolytic processing of the amyloid precursor protein. We investigated the molecular mechanisms underlying cell death and ER dysfunction in cultured cells and knock-in mice expressing FAD PS1 mutations. We report that PS1 mutations cause a marked increase in basal protein levels of the pro-apoptotic transcript...
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