Biomedical subjects

Enakshi Chakrabarti

Publications and source records attributed to Enakshi Chakrabarti.

4 recordsLinked to original sources

PubMed2006

Transcriptome profile of macrophages from atherosclerosis-sensitive and atherosclerosis-resistant mice.

We performed a strain intercross between two apoE-deficient mouse strains with a large difference in lesion susceptibility and measured aortic root lesion area in 98 female F(2) progeny. Total RNA was prepared from bone marrow-derived macrophages, and RNA from the five mice with the smallest and largest lesions were used for microarray gene expression profiling. Remarkably, approximately 5% of the 12,288 expressed transcripts were differentially expressed in the atherosclerosis-susceptible and atherosclerosis-resistant bone marrow-derived macrophages (unadjusted p < 0.05), thus defining the transcriptome of macrophages associated with atherosclerosis susceptibility. Using more stringent criteria of twofold or greater change and p < 0.01, 116 and 70 transcripts were overexpressed in lesion-prone and lesion-resistant bone marrow-derived macrophages, respectively. Transcription factor binding site analysis identified two promoter elements that were found more often in the genes overexpressed in the large-lesion group, and one promoter element that was found more often in the small-lesion group. The combination of this expression profiling data with the genetic method of quantitative trait locus mapping should give powerful insights into the genes that affect atherosclerosis susceptibility in mice.

Alternative Splicing↗

PubMed2005

Ultraviolet light (UVB and UVA) induces the damage-responsive transcription factor CHOP/gadd153 in murine and human epidermis: evidence for a mechanism specific to intact skin.

C/EBP-homologous protein (CHOP)/gadd153 (or CHOP) is a transcription factor induced by endoplasmic reticulum (ER) stress. Forcible overexpression of CHOP causes apoptosis in keratinocytes in culture. Here, we asked whether CHOP might be increased in the skin after UVB (280-320 nm) exposure, thus implicating CHOP in sunburn cell (SBC) formation. SKH-1 hairless mice were exposed to a ultraviolet (UV) source (80 mJ per cm2; approximately 74% UVB, approximately 16% UVA), and skin biopsies examined by immunohistology and immunoprecipitation. Compared with non-irradiated epidermis, CHOP expression was significantly increased at 30 min, and reached maximal levels by 24 h. Similar increases in CHOP following UVB exposure were observed in human buttock skin. The time course of CHOP expression preceded SBC formation and another marker of apoptosis, caspase-3 cleavage. Intracellular CHOP accumulated mainly in cytoplasmic and perinuclear locations, with little remaining in the nucleus. To examine mechanisms, cultured keratinocytes were irradiated in vitro and examined by western blotting. Under conditions that eliminated ER stress because of cell handling, CHOP did not accumulate (and was in fact decreased) in the cells. Thus, induction of CHOP in keratinocytes requires factors present only in the native skin. Overall, the data suggest that CHOP participates in adaptive responses of the epidermis following UVB/UVA exposure in vivo.

Animals↗

PubMed2005

Drug library screen to identify compounds that decrease secreted Abeta from a human cell line.

In order to discover compounds that may be useful in the prevention of Alzheimer disease, a drug library was screened for drugs that could decrease amyloid beta peptide (Abeta) accumulation secreted from a human CNS-derived cell line. Of the 2160 compounds subjected to a primary screen, 16, or 0.74%, reduced Abeta accumulation by at least 40%. Seven of these compounds were confirmed to be effective in a secondary screen using each compound at a dose of 5 microM. Three of these seven compounds were more effective than the others at reducing Abeta levels in a tertiary screen, and led to 68 to 85% reductions in total Abeta, at the 25 microM dosage. The effects of these three drugs on secreted Abeta40, Abeta42, and sAPPalpha were also determined. Thus, we have identified lead compounds that may be useful for subsequent studies to determine the mechanism of action of each drug, as well as for pre-clinical studies to determine whether each of these drugs is safe and effective in vivo.

Amyloid beta-Peptides↗

PubMed2004

Drug discovery: estrogen-related compounds in mouse models of Alzheimer's disease.

Despite promising epidemiological studies that showed a decreased incidence of Alzheimer disease (AD) in women who used hormone replacement therapy (HRT), the results of the recently released Women's Health Initiative Memory Study has dampened any enthusiasm for the use of HRT in women to prevent or delay the onset of AD. In this position paper, we review these data, along with our own--using estrogens in a transgenic mouse model of AD--and introduce our current working hypothesis and research.

Alzheimer Disease↗