Nambi K.S.N.,C Abdul Hakeem College |
Majeed S.A.,C Abdul Hakeem College |
Taju G.,C Abdul Hakeem College |
Sivasubbu S.,Institute of Genomics and Integrative Biology IGIB |
And 3 more authors.
Zebrafish | Year: 2015
Danio rerio retinal pigmented epithelial (DrRPE) cell line, derived from the RPE tissue, was established and characterized. The cells were able to grow at a wide range of temperatures from 25°C to 32°C in Leibovitz's L-15 medium. The DrRPE cell line consists of epithelial cells with a diameter of 15-19 μm. The cell line was characterized by mitochondrial 12S rRNA gene, immunocytochemical analysis, and karyotyping. DrRPE cells treated with 10 μM of all-trans-retinol for 24 h readily formed lipid droplets. DrRPE cells were irradiated with narrowband ultraviolet-B (UV-B) radiation at different time periods of 0, 10, 20, and 40 min. The cells were subsequently examined for changes in morphology, cell viability, phagocytotic activity, mitochondrial distribution, nuclei morphology, generation of reactive oxygen species, and expression of apoptotic-related genes p53 and Cas3 by quantitative polymerase chain reaction. The results demonstrate that UV-B radiation can cause a considerable decrease in DrRPE cell viability as well as in phagocytotic activity. In addition, the results demonstrate that UV-B radiation can induce the degradation of mitochondria and DNA in cultured DrRPE cells. © Copyright 2015, Mary Ann Liebert, Inc. 2015.
Motiani R.K.,University at Albany |
Motiani R.K.,Institute of Genomics and Integrative Biology IGIB |
Stolwijk J.A.,University at Albany |
Newton R.L.,University at Albany |
And 2 more authors.
Channels | Year: 2013
Calcium (Ca2+) is a ubiquitous second messenger that regulates a plethora of physiological functions. Deregulation of calcium homeostasis has been reported in a wide variety of pathological conditions including cardiovascular disorders, cancer and neurodegenerative diseases. One of the most ubiquitous pathways involved in regulated Ca2+ influx into cells is the store-operated Ca2+ entry (SOCE) pathway. In 2006, Orai1 was identified as the channel protein that mediates SOCE in immune cells. Orai1 has two mammalian homologs, Orai2 and Orai3. Although Orai1 has been the most widely studied Orai isoform, Orai3 has recently received significant attention. Under native conditions, Orai3 was demonstrated to be an important component of store-independent arachidonate-regulated Ca2+ (ARC) entry in HEK293 cells, and more recently of a store-independent leukotrieneC4- regulated Ca2+ (LRC) entry pathway in vascular smooth muscle cells. Recent studies have shown upregulation of Orai3 in estrogen receptor-expressing breast cancers and a critical role for Orai3 in breast cancer development in immune-compromised mice. Orai3 upregulation was also shown to contribute to vascular smooth muscle remodeling and neointimal hyperplasia caused by vascular injury. Furthermore, Orai3 has been shown to contribute to proliferation of effector T-lymphocytes under oxidative stress. In this review, we will discuss the role of Orai3 in reported pathophysiological conditions and will contribute ideas on the potential role of Orai3 in native Ca2+ signaling pathways and human disease. © 2013 Landes Bioscience.
Mohanty D.,National Institute of Immunology |
Sankaranarayanan R.,Center for Cellular and Molecular Biology |
Gokhale R.S.,Institute of Genomics and Integrative Biology IGIB |
Gokhale R.S.,Jawaharlal Nehru Center for Advanced Scientific Research
Tuberculosis | Year: 2011
The cell envelope of Mycobacterium tuberculosis (Mtb) possesses a repertoire of unusual lipids that are believed to play an important role in pathogenesis. In this review, we specifically focus on computational, biochemical and structural studies in lipid biosynthesis that have established functional role of polyketide synthases (PKSs) and fatty acyl-AMP ligases (FAALs). Mechanistic and structural studies with FAALs suggest that this group of proteins may have evolved from omnipresent fatty acyl-CoA ligases (FACLs). FAALs activate fatty acids as acyl-adenylates and transfer them on to the PKSs which then produce unusual acyl chains that are the components of mycobacterial lipids. FAALs are a newly discovered family of enzymes; whereas involvement of PKSs in lipid metabolism was not known prior to their discovery in Mtb. Since Mtb genome contains multiple homologs of FAALs and PKSs and owing to the conserved reaction mechanism and overlapping substrate specificity; there is tempting opportunity to develop 'systemic drugs' against these enzymes as anti-tuberculosis agents. © 2011 Elsevier Ltd. All rights reserved.
Gupta A.C.,Jamia Millia Islamia University |
Chaudhory A.K.,GB Pant Hospital |
Sukriti,GB Pant Hospital |
Pande C.,GB Pant Hospital |
And 4 more authors.
Hepatology International | Year: 2011
Background: Non-alcoholic fatty liver disease (NAFLD) is a major cause of chronic liver disease globally and commonly associated with insulin resistance and metabolic syndrome (MS). Peroxisome proliferator-activated receptor-γ (PPARγ) is a transcription factor abundantly expressed in adipocytes and plays a key role in the regulation of adipocyte differentiation, lipid and glucose homeostasis. Pro12Ala variant has been earlier associated with obesity, type 2 diabetes and MS. Aim: The present study aimed to determine the genotype frequencies of the Pro12Ala variant in NAFLD patients and any further association with other phenotype in the patients. Patients and methods: Ninety-eight NAFLD patients and 280 matched controls were genotyped for presence of the Pro12Ala variant. Genomic DNA was extracted and polymerase chain reaction-restriction fragment length polymorphism using Bst-UI was performed for the detection of C-G change at codon 12 position of PPAR γ2 gene. Genotype and allele frequencies were compared between patients and controls. The Hardy-Weinberg equilibrium was tested by comparing expected/observed genotype frequencies by χ 2 test. Results: The frequencies of Pro/Ala genotype were comparable between NAFLD patients and controls. In the controls, 213 (75.7%) were homozygous for the wild-type (Pro/Pro) genotype and 67 (23.9%) were heterozygous (Pro/Ala). In NAFLD patients, genotypic distribution of wild type, heterozygous and homozygous were 63 (64.3%), 34 (34.7%) and 1 (1%), respectively. Heterozygous genotype was found to be significantly higher in the patients (P = 0.01). We also analyzed related phenotypic association of the patients with Pro12Ala genotype. We observed that the Pro12Ala (heterozygous) genotype was significantly higher in the patients who had body mass index >25 kg/m 2 (P = 0.025). Conclusions: Pro12Ala variation of the PPAR γ2 gene is associated with NAFLD and might play a role in the pathogenesis of NAFLD. © 2010 Asian Pacific Association for the Study of the Liver.
Steinbicker A.U.,Harvard University |
Steinbicker A.U.,University of Munster |
Sachidanandan C.,Harvard University |
Sachidanandan C.,Institute of Genomics and Integrative Biology IGIB |
And 16 more authors.
Blood | Year: 2011
Anemia of inflammation develops in settings of chronic inflammatory, infectious, or neoplastic disease. In this highly prevalent form of anemia, inflammatory cytokines, including IL-6, stimulate hepatic expression of hepcidin, which negatively regulates iron bioavailability by inactivating ferroportin. Hepcidin is transcriptionally regulated by IL-6 and bone morphogenetic protein (BMP) signaling. We hypothesized that inhibiting BMP signaling can reduce hepcidin expression and ameliorate hypoferremia and anemia associated with inflammation. In human hepatoma cells, IL-6-induced hepcidin expression, an effect that was inhibited by treatment with a BMP type I receptor inhibitor, LDN-193189, or BMP ligand antagonists noggin and ALK3-Fc. In zebrafish, the induction of hepcidin expression by transgenic expression of IL-6 was also reduced by LDN-193189. In mice, treatment with IL-6 or turpentine increased hepcidin expression and reduced serum iron, effects that were inhibited by LDN-193189 or ALK3-Fc. Chronic turpentine treatment led to microcytic anemia, which was prevented by concurrent administration of LDN-193189 or attenuated when LDN-193189 was administered after anemia was established. Our studies support the concept that BMP and IL-6 act together to regulate iron homeostasis and suggest that inhibition of BMP signaling may be an effective strategy for the treatment of anemia of inflammation. © 2011 by The American Society of Hematology.