Biomedical subjects

Deepak Kaul

Publications and source records attributed to Deepak Kaul.

12 recordsLinked to original sources

PubMed2006

Functional characterization of AATF transcriptome in human leukemic cells.

The study, addressed to explore the transcriptional expression and regulation of Apoptosis-antagonizing transcription factor (AATF) gene within various types of human leukemic cell lines, revealed that AATF gene was overexpressed ubiquitously in all the leukemic cell lines studied and this upregulation was accompanied by c-myc gene overamplification in these cells. Downregulation of AATF gene transcription within leukemic cells not only resulted in the downregulation of c-myc gene and vice-versa but also contributed to apoptosis leading to cell death. Further, the link between AATF expression and leukemic cellular apoptosis involved PI3K/Akt pathway. Based on these results we propose that AATF gene may be of crucial importance in maintaining the leukemic state of a cell compartment through its ability to initiate cell proliferation coupled with repression of cellular apoptosis.

Androstadienes↗

PubMed2006

Importance of LXR-alpha transcriptome in the modulation of innate immunity.

Liver-X-Receptor alpha (LXR-alpha) that belongs to nuclear receptor/transcriptional factor family has been recognized to play crucial role in the regulation of lipid metabolism and inflammation. Consequently, the present study was addressed to explore the functional genomics of LXR-alpha within human blood immunomodulatory cells. The results of such a study, which involved LXR-alpha gene silencing through siRNA approach, revealed that: (a) the mRNA expression of genes coding for IL-8, IL-4, CX3CR1, LDLR, hTERT and c-myc was significantly elevated in response to LXR-alpha gene silencing whereas mRNA expression of genes coding for PPARs(alpha, gamma), CD36 and Dicer could not be detected; (b) the expression of Receptor C( k ) protein remained unaffected; (c) the mRNA expression of IFN-gamma gene was down regulated in LXR-alpha knockdown cells. Based upon these results we propose that LXR-alpha gene plays a crucial role in the regulation of innate immunity at the genomic level.

CD36 Antigens↗

PubMed2006

Pathognomonic genetic expression profile within peripheral blood mononuclear cells of rheumatic heart disease patients.

The present study was addressed to understand as to how the expression of genes, that play crucial role in both inflammation and autoimmune process, within blood mononuclear cells are effected by the molecular mimicry between streptococcal antigen and heart tissue recognized as main contributor towards the genesis of rheumatic heart disease (RHD). Such a study for the first time revealed that as compared to genomic profile within normal blood mononuclear cells, the cells derived from rheumatic heart disease patients exhibited significantly higher expression of genes coding for IL-8, IFN-gamma and CX3CR1 coupled with significant downregulation of CD36 mRNA expression. Based upon these results, we propose that maintenance of such a pathognomonic transcriptome within blood mononuclear cells may be responsible for the initiation and progression of rheumatic heart disease.

Adult↗

PubMed2006

Functional genomics of PPAR-gamma in human immunomodulatory cells.

Keeping in view the fact that peroxisome-proliferators activated receptors-PPARs (alpha,gamma) play a crucial role in atherogenic inflammation, the present study was addressed to explore as to how selective and specific PPAR-gamma gene silencing within human mononuclear cells affects genes involved in lipid metabolism and innate immune process. Such a study revealed that with respect to control cells, the PPAR-gamma knock-out cells exhibited significant reduction in the expression of genes coding for PPAR- alpha, CD-36, LDL-R as well as significant increase in the expression of genes coding for IL-4, IL-8, IFN-gamma, CX3CR1, hTERT. However, the expression of genes coding for LXR-alpha and Receptor-C( k ) could not be detected in PPAR-gamma knock-out cells. Based on these results, we propose that PPAR-gamma gene has the inherent capacity to influence the lipid mediated inflammation process in atherosclerotic lesions.

Cells, Cultured↗

PubMed2006

Receptor Ck-dependent signaling regulates hTERT gene transcription.

BACKGROUND: Available evidence suggests that the regulation of telomerase activity primarily depends on the transcriptional control of the human telomerase reverse transcriptase (hTERT) gene. Although several activators and repressors of hTERT gene transcription have been identified, the exact mechanism by which hTERT transcription is repressed in normal cells and activated in cancer cells remains largely unknown. In an attempt to identify possible novel mechanisms involved in the regulation of hTERT transcription, the present study examined the role of Receptor Ck, a cell surface receptor specific for cholesterol, in the transcription of hTERT gene in normal human peripheral blood mononuclear cells. RESULTS: Activated Receptor Ck was found to down-regulate hTERT mRNA expression by repressing the transcription of c-myc gene. Receptor Ck-dependent signaling was also found to down-regulate the mRNA expression of the gene coding for the ligand inducible transcription factor, peroxisome proliferator-activated receptor gamma (PPARgamma). The ligand activation of PPARgamma resulted in the down-regulation of c-myc and hTERT mRNA expression. By using specific activator and inhibitor of protein kinase C (PKC), it was demonstrated that Receptor Ck dependent down-regulation of hTERT gene transcription involved inhibition of PKC. In addition, 25-hydroxycholesterol was found to contribute to the transcriptional regulation of hTERT gene. CONCLUSION: Taken together, the findings of this study present evidence for a molecular link between cholesterol-activated Receptor Ck and hTERT transcription, and provide new insights into the regulation of hTERT expression in normal human peripheral blood mononuclear cells.

Cells, Cultured↗

PubMed2006

Green tea polyphenol inhibits Mycobacterium tuberculosis survival within human macrophages.

Lack of maturation of phagosomes containing pathogenic Mycobacterium tuberculosis within macrophages has been widely recognized as a crucial factor for the persistence of mycobacterial pathogen. Host molecule tryptophan-aspartate containing coat protein (TACO) has been shown to play a crucial role in the arrest of such a maturation process. The present study was addressed to understand whether or not polyphenols derived from green tea could down-regulate TACO gene transcription. And if yes, what impact TACO gene down-regulation has on the uptake/survival of M. tuberculosis within macrophages. The reverse-transcriptase polymerase chain reaction and reporter assay technology, employed in this study, revealed that the major component of green tea polyphenols, epigallocatechin-3-gallate had the inherent capacity to down-regulate TACO gene transcription within human macrophages through its ability to inhibit Sp1 transcription factor. We also found out that TACO gene promoter does contain Sp1 binding sequence using bioinformatics tools. The down-regulation of TACO gene expression by epigallocatechin-3-gallate was accompanied by inhibition of mycobacterium survival within macrophages as assessed through flow cytometry and colony counts. Based on these results, we propose that epigallocatechin-3-gallate may be of importance in the prevention of tuberculosis infection.

Antioxidants↗

PubMed2005

Importance of blood cellular genomic profile in coronary heart disease.

Since receptor/transcription factor family especially peroxisome proliferator-activated receptors PPARs (alpha, gamma) and liver X receptor alpha (LXRalpha) have been recognized to play crucial role in both lipid metabolism and inflammation, the present study was addressed to explore the interrelationship between blood cellular genomic expression profile, serum lipid levels and severity of coronary heart disease (CHD) in human subjects. Based upon the demographic and laboratory data, the human subjects were divided into 4 groups. Genomic expression profile in the subjects belonging to these groups was determined by measuring the transcriptional expression of genes coding for PPARs (alpha, gamma), CD36, LXRalpha and low density lipoprotein receptor (LDLR) in their blood mononuclear cells. This genomic expression profile was correlated with serum lipid profile as well as with the severity of CHD (revealed by coronary angiography coupled with modified Gensini score) using standard statistical analytical methods. Further in vitro and in vivo effect of statins on such genomic profile was also explored. Although genes coding for PPARs (alpha, gamma), CD36, LDLR showed correlation with the severity of coronary atherosclerosis , blood cellular LXRalpha genomic profile showed conspicuous negative correlation with the severity of coronary atherosclerosis in subjects with or without hypercholesterolemia. This view was further confirmed in experiments directed to understand the effect of statins on the cellular genomic profile of PPARs (alpha, gamma) and LXRalpha. Based on these reported findings, we propose that blood cellular LXRalpha genomic profile has a protective effect against the development of CHD and hence may be of importance in devising synthetic therapeutic drugs for CHD in future.

Adult↗

PubMed2005

Downregulation of TACO gene transcription restricts mycobacterial entry/survival within human macrophages.

Recent reports have indicated that cholesterol-dependent association of tryptophan-aspartate containing coat protein (TACO) plays a crucial role in the entry/survival of Mycobacterium tuberculosis within human macrophages. Keeping this in view, the present study explored whether the molecules that have the ability to downregulate TACO gene transcription could also restrict entry/survival of mycobacteria within human macrophages. The study revealed that chenodeoxycholic acid (CDCA), either alone or in combination with retinoic acid (RA), had the inherent capacity to downregulate TACO gene transcription in a dose-dependent fashion. This result was in conformity with the existence of a functional FXR/RXR binding site analyzed in the regulatory region of the TACO gene. Furthermore, we demonstrate that the entry and intracellular survival of M. tuberculosis is significantly restricted in THP-1 macrophages exposed to CDCA/RA. On the basis of these findings, we propose that the CDCA/RA-dependent pathway may open a new possibility for the treatment of tuberculosis.

Base Sequence↗

PubMed2005

Effect of herbal polyphenols on atherogenic transcriptome.

The ancient Indian system of medicine supports the antiatherogenic properties of some herbs. The crosstalk amongst the genes coding for LDLR, LXRalpha, PPARs (alpha,gamma), CD-36 and c-myc may be important in atherogenesis because these genes control lipid metabolism, cytokine production and cellular activity within the arterial wall. Hence, we attempted for the first time to explore whether or not the polyphenols extracted from medicinal herbs had any effect on the transcription of these genes. Normal human mononuclear cells were cultured in the presence of polyphenols (and their HPLC purified sub-fractions) extracted from Green tea (Camellia sinensis), Neem (Azadirachta indica) and Tulsi (Ocimum sanctum). Transcriptional expression of these genes was measured by using RT-PCR and SCION IMAGE analysis software. These polyphenolic extracts were found to have the inherent capacity to inhibit the transcriptional expression of genes having direct involvement in atherogenic process. On the basis of these results, we propose for the first time that HPLC purified polyphenolic fraction IV of Tulsi may have a profound antiatherogenic effect.

Atherosclerosis↗

PubMed2004

Defective RNA-mediated c-myc gene silencing pathway in Burkitt's lymphoma.

Keeping in view the fact that molecular basis of Burkitt's lymphoma (BL) is poorly understood, we attempted to explore the small interfering RNA (siRNA) mediated c-myc gene regulation using BL-derived EB-3 cell line as archetype cellular model. Such a study revealed that EB-3 cells possess 4-fold higher expression of Dicer gene coupled with 2-fold higher activity of RNA polymerase III than that observed in normal human lymphocytes. siRNAs derived from EB-3 cells had the inherent capacity to suppress c-myc gene expression in normal cells but not in native cells. Based on these findings we have proposed a novel RNA-mediated c-myc gene regulation pathway that may be responsible for BL.

Burkitt Lymphoma↗

PubMed2003

Vitamin D3-dependent pathway regulates TACO gene transcription.

Recently, gene coding for tryptophan-aspartate containing coat protein (TACO) has been recognized to play a crucial role in the survival of Mycobacterium tuberculosis within human macrophages. Since regulation of TACO gene is still poorly understood, the present study was addressed to explore the role of vitamins (A, C, D, and E) in TACO gene transcription. Such a study revealed that synergistic action of vitamin D(3) and retinoic acid (RA) had inherent ability to down-regulate TACO gene transcription in human macrophages. Based upon these results, we propose that synergistic action of RA+vitamin D may be of importance in the prevention/control of M. tuberculosis infection.

Cholecalciferol↗

PubMed2003

Cholesterol-receptor-mediated genomics in health and disease.

Cross-talk between cell-surface receptor C(k) and intracellular receptors (liver X receptor-alpha and peroxisome-proliferator-activated receptors) controls a set of crucial genes that maintain a finely orchestrated balance between various cellular processes involved in cell growth, differentiation, apoptosis, cholesterol homeostasis and inflammation. Abnormal cross-talk of these receptors can lead to several human diseases, particularly atherosclerosis, cancer and autoimmune diseases. As our understanding of the complex signaling events that link these receptors to human health improves, we are beginning to appreciate the enormous potential of the proposed cross-talk model of cholesterol receptors in the prevention and/or treatment of diseases.

Animals↗