Search

Your search keyword '"Shridas, Preetha"' showing total 141 results
Start Over Author "Shridas, Preetha"
141 results on '"Shridas, Preetha"'

2. Inflammation and Tumor Progression: The Differential Impact of SAA in Breast Cancer Models.

Author

Olivier, Daniel Wilhelm, Eksteen, Carla, Plessis, Manisha du, de Jager, Louis, Engelbrecht, Lize, McGregor, Nathaniel Wade, Shridas, Preetha, de Beer, Frederick C., de Villiers, Willem J. S., Pretorius, Etheresia, and Engelbrecht, Anna-Mart

Subjects
TRIPLE-negative breast cancer, PATHOLOGY, STAINS & staining (Microscopy), MOLECULAR biology, BREAST tumors
Abstract

Simple Summary: Previous research highlights the involvement of the Serum Amyloid A (SAA) protein family in inflammation and various diseases. This study explores the role of SAA1 and SAA2 (SAA1/2) in triple-negative breast cancer using a mouse model. Syngeneic breast tumors were established in wild-type and SAA1/2-deficient (SAADKO) mice, with assessments of tumor volume, survival, inflammatory profiles, and tumor characteristics. Background: Previous research has shown that the Serum Amyloid A (SAA) protein family is intricately involved in inflammatory signaling and various disease pathologies. We have previously demonstrated that SAA is associated with increased colitis disease severity and the promotion of tumorigenesis. However, the specific role of SAA proteins in breast cancer pathology remains unclear. Therefore, we investigated the role of systemic SAA1 and SAA2 (SAA1/2) in a triple-negative breast cancer mouse model. Methods: Syngeneic breast tumors were established in wild-type mice, and mice lacking the SAA1/2 (SAADKO). Subsequently, tumor volume was monitored, species survival determined, the inflammatory profiles of mice assessed with a multiplex assay, and tumor molecular biology and histology characterized with Western blotting and H&E histological staining. Results: WT tumor-bearing mice had increased levels of plasma SAA compared to wild-type control mice, while SAADKO control and tumor-bearing mice presented with lower levels of SAA in their plasma. SAADKO tumor-bearing mice also displayed significantly lower concentrations of systemic inflammatory markers. Tumors from SAADKO mice overall had lower levels of SAA compared to tumors from wild-type mice, decreased apoptosis and inflammasome signaling, and little to no tumor necrosis. Conclusions: We demonstrated that systemic SAA1/2 stimulates the activation of the NLRP3 inflammasome in breast tumors, leading to the production of pro-inflammatory cytokines. This, in turn, promoted apoptosis and tumor necrosis but did not significantly impact tumor growth or histological grading. [ABSTRACT FROM AUTHOR]

Published
2024
Full Text
View/download PDF

4. Deficiency of Acute-Phase Serum Amyloid A Exacerbates Sepsis-Induced Mortality and Lung Injury in Mice

Author

Ji, Ailing, primary, Trumbauer, Andrea C., additional, Noffsinger, Victoria P., additional, Meredith, Luke W., additional, Dong, Brittany, additional, Wang, Qian, additional, Guo, Ling, additional, Li, Xiangan, additional, De Beer, Frederick C., additional, Webb, Nancy R., additional, Tannock, Lisa R., additional, Starr, Marlene E., additional, Waters, Christopher M., additional, and Shridas, Preetha, additional

Published
2023
Full Text
View/download PDF

6. Antisense Oligonucleotide Targeting Hepatic Serum Amyloid A Limits the Progression of Angiotensin II-Induced Abdominal Aortic Aneurysm Formation

Author

Shridas, Preetha, primary, Ji, Ailing, additional, Trumbauer, Andrea C, additional, Noffsinger, Victoria P, additional, Meredith, Luke W, additional, de Beer, Frederick C., additional, Mullick, Adam E, additional, Webb, Nancy R., additional, Karounos, Dennis G, additional, and Tannock, Lisa R, additional

Published
2023
Full Text
View/download PDF

10. Beyond the acute-phase response: systemic Serum Amyloid A 1/2 promotes inflammasome activation, apoptosis, and necrosis in breast cancer

Author

Olivier, Daniel Wilhelm, primary, Fourie, Carla, additional, du Plessis, Manisha, additional, de Jager, Louis Johann, additional, Engelbrecht, Lize, additional, McGregor, Nathaniel Wade, additional, Shridas, Preetha, additional, de Beer, Frederick C, additional, de Villiers, Willem Johan Simon, additional, Pretorius, Etheresia, additional, and Engelbrecht, Anna-Mart, additional

Published
2022
Full Text
View/download PDF

14. Adipocyte-Derived Serum Amyloid A Promotes Angiotensin II–Induced Abdominal Aortic Aneurysms in Obese C57BL/6J Mice

Author

Shridas, Preetha, primary, Ji, Ailing, additional, Trumbauer, Andrea C., additional, Noffsinger, Victoria P., additional, Leung, Steve W., additional, Dugan, Adam J., additional, Thatcher, Sean E., additional, Cassis, Lisa A., additional, de Beer, Frederick C., additional, Webb, Nancy R., additional, and Tannock, Lisa R., additional

Published
2022
Full Text
View/download PDF

26. Expression and characterization of a human cDNA that complements the temperature-sensitive defect in dolichol kinase activity in the yeast sec59-1 mutant: the enzymatic phosphorylation of dolichol and diacylglycerol are catalyzed by separate CTP-mediated kinase activities in Saccharomyces cerevisiae

Author

Fernandez, Fabiana, Shridas, Preetha, Jiang, Songmin, Aebi, Markus, Waechter, Charles J., Fernandez, Fabiana, Shridas, Preetha, Jiang, Songmin, Aebi, Markus, and Waechter, Charles J.

Abstract

Dolichol kinase (DK) catalyzes the CTP-mediated phosphorylation of dolichol in eukaryotic cells, the terminal step in dolichyl monophosphate (Dol-P) biosynthesis de novo. In S. cerevisiae, the SEC59 gene encodes a protein essential for the expression of DK, an enzyme activity that is required for cell viability and normal rates of lipid intermediate synthesis and protein N-glycosylation. This study identifies a cDNA clone from human brain that encodes the mammalian homolog of DK (hDK1p). hDK1 is capable of complementing the growth defect, elevating DK activity, and consequently increasing Dol-P levels in vivo and restoring normal N-glycosylation of carboxypeptidase Y at the restrictive temperature in the temperature-sensitive mutant sec59-1. The CTP-mediated phosphorylation of diacylglycerol (DAG) is unaffected by either the temperature-sensitive mutation in the sec59-1 strain, overexpression of the SEC59 gene, or the mammalian homolog hDK1 under conditions that produced a loss or elevation in the level of DK activity. Additionally, overexpression of hDK1p in Sf-9 cells resulted in a 15-fold increase in DK activity but not DAG kinase activity in crude microsomal fractions. The cloned cDNA contains an open reading frame that would encode a protein with 538 amino acids and a molecular weight of 59,268 kDa. Consistent with this prediction, new polypeptides were detected with an apparent molecular weight of 59-60 kDa when His6-tagged constructs of hDK1 or the SEC59 gene were expressed in Sf-9 cells or the temperature-sensitive sec59-1 mutant cells, respectively. These results identify the first cDNA clone encoding a protein required for the expression of DK activity, possibly the catalytic subunit, in a mammalian cell, and establish that the phosphorylation of dolichol and DAG are catalyzed by separate kinase activities in yeast

Published
2017

28. Group X Secretory Phospholipase A2 Enhances Toll-Like Receptor 4 Signaling in Macrophages

Author

Shridas, Preetha, Bailey, William M, Talbott, Kayla R, Oslund, Rob C, Gelb, Michael H, and Webb, Nancy R

Subjects
Lipopolysaccharides, Male, Mice, Knockout, Macrophages, Article, Cell Line, Mice, Inbred C57BL, Toll-Like Receptor 4, Mice, Cholesterol, Membrane Microdomains, Animals, Group X Phospholipases A2, Homeostasis, lipids (amino acids, peptides, and proteins), Female, Signal Transduction
Abstract

Secretory phospholipase A(2)s (sPLA(2)) hydrolyze glycerophospholipids to liberate lysophospholipids and free fatty acids. Although group X (GX) sPLA(2) is recognized as the most potent mammalian sPLA(2) in vitro, its precise physiological function(s) remains unclear. We recently reported that GX sPLA(2) suppresses activation of the liver X receptor in macrophages, resulting in reduced expression of liver X receptor-responsive genes including ATP-binding cassette transporters A1 (ABCA1) and G1 (ABCG1), and a consequent decrease in cellular cholesterol efflux and increase in cellular cholesterol content (Shridas et al. 2010. Arterioscler. Thromb. Vasc. Biol. 30: 2014-2021). In this study, we provide evidence that GX sPLA(2) modulates macrophage inflammatory responses by altering cellular cholesterol homeostasis. Transgenic expression or exogenous addition of GX sPLA(2) resulted in a significantly higher induction of TNF-α, IL-6, and cyclooxygenase-2 in J774 macrophage-like cells in response to LPS. This effect required GX sPLA(2) catalytic activity, and was abolished in macrophages that lack either TLR4 or MyD88. The hypersensitivity to LPS in cells overexpressing GX sPLA(2) was reversed when cellular free cholesterol was normalized using cyclodextrin. Consistent with results from gain-of-function studies, peritoneal macrophages from GX sPLA(2)-deficient mice exhibited a significantly dampened response to LPS. Plasma concentrations of inflammatory cytokines were significantly lower in GX sPLA(2)-deficient mice compared with wild-type mice after LPS administration. Thus, GX sPLA(2) amplifies signaling through TLR4 by a mechanism that is dependent on its catalytic activity. Our data indicate this effect is mediated through alterations in plasma membrane free cholesterol and lipid raft content.

Published
2011

30. Deficiency of Endogenous Acute-Phase Serum Amyloid A Protects apoE −/− Mice From Angiotensin II–Induced Abdominal Aortic Aneurysm Formation

Author

Webb, Nancy R., primary, De Beer, Maria C., additional, Wroblewski, Joanne M., additional, Ji, Ailing, additional, Bailey, William, additional, Shridas, Preetha, additional, Charnigo, Richard J., additional, Noffsinger, Victoria P., additional, Witta, Jassir, additional, Howatt, Deborah A., additional, Balakrishnan, Anju, additional, Rateri, Debra L., additional, Daugherty, Alan, additional, and De Beer, Frederick C., additional

Published
2015
Full Text
View/download PDF

34. Deficiency of Endogenous Acute Phase Serum Amyloid A Does Not Affect Atherosclerotic Lesions in Apolipoprotein E–Deficient Mice

Author

De Beer, Maria C., primary, Wroblewski, Joanne M., additional, Noffsinger, Victoria P., additional, Rateri, Debra L., additional, Howatt, Deborah A., additional, Balakrishnan, Anju, additional, Ji, Ailing, additional, Shridas, Preetha, additional, Thompson, Joel C., additional, van der Westhuyzen, Deneys R., additional, Tannock, Lisa R., additional, Daugherty, Alan, additional, Webb, Nancy R., additional, and De Beer, Frederick C., additional

Published
2014
Full Text
View/download PDF

36. Perinatal exercise improves glucose homeostasis in adult offspring

Author

Carter, Lindsay G., primary, Lewis, Kaitlyn N., additional, Wilkerson, Donald C., additional, Tobia, Christine M., additional, Ngo Tenlep, Sara Y., additional, Shridas, Preetha, additional, Garcia-Cazarin, Mary L., additional, Wolff, Gretchen, additional, Andrade, Francisco H., additional, Charnigo, Richard J., additional, Esser, Karyn A., additional, Egan, Josephine M., additional, de Cabo, Rafael, additional, and Pearson, Kevin J., additional

Published
2012
Full Text
View/download PDF

38. The dual role of group V secretory phospholipase A2in pancreatic β-cells

Author

Shridas, Preetha, Noffsinger, Victoria, Trumbauer, Andrea, and Webb, Nancy

Abstract

Group X (GX) and group V (GV) secretory phospholipase A2(sPLA2) potently release arachidonic acid (AA) from the plasma membrane of intact cells. We previously demonstrated that GX sPLA2negatively regulates glucose-stimulated insulin secretion (GSIS) by a prostaglandin E2 (PGE2)-dependent mechanism. In this study we investigated whether GV sPLA2similarly regulates GSIS. GSIS and pancreatic islet-size were assessed in wild-type (WT) and GV sPLA2-knock out (GV KO) mice. GSIS was also assessed ex vivo in isolated islets and in vitro using MIN6 pancreatic beta cell lines with or without GV sPLA2overexpression or silencing. GSIS was significantly decreased in islets isolated from GV KO mice compared to WT mice and in MIN6 cells with siRNA-mediated GV sPLA2suppression. MIN6 cells overexpressing GV sPLA2(MIN6-GV) showed a significant increase in GSIS compared to control cells. Though the amount of AA released into the media by MIN6-GV cells was significantly higher, PGE2 production was not enhanced or cAMP content decreased compared to control MIN6 cells. Surprisingly, GV KO mice exhibited a significant increase in plasma insulin levels following i.p. injection of glucose compared to WT mice. This increase in GSIS in GV KO mice was associated with a significant increase in pancreatic islet size and number of proliferating cells in β-islets compared to WT mice. Deficiency of GV sPLA2results in diminished GSIS in isolated pancreatic beta-cells. However, the reduced GSIS in islets lacking GV sPLA2appears to be compensated by increased islet mass in GV KO mice.

Published
2017
Full Text
View/download PDF

40. Group X secretory phospholipase A2 augments angiotensin II-induced inflammatory responses and abdominal aortic aneurysm formation in apoE-deficient mice

Author

Zack, Melissa, primary, Boyanovsky, Boris B., additional, Shridas, Preetha, additional, Bailey, William, additional, Forrest, Kathy, additional, Howatt, Deborah A., additional, Gelb, Michael H., additional, de Beer, Frederick C., additional, Daugherty, Alan, additional, and Webb, Nancy R., additional

Published
2011
Full Text
View/download PDF

49. Ectopically Expressed Pro-group X Secretory Phospholipase A2 Is Proteolytically Activated in Mouse Adrenal Cells by Furin-like Proprotein Convertases.

Author

Layne, Joseph D., Shridas, Preetha, and Webb, Nancy R.

Subjects
*ZYMOGENS, *PROPROTEIN convertases, *PHOSPHOLIPASES, *FREE fatty acids, *BIOCHEMICAL research
Abstract

Group X secretory phospholipase A2 (GX sPLA2) hydrolyzes mammalian cell membranes, liberating free fatty acids and lysophospholipids. GX sPLA2 is produced as a pro-enzyme (pro-GX sPLA2) that contains an N-terminal 11-amino acid propeptide ending in a dibasic motif, suggesting cleavage by a furin-like proprotein convertase (PC). Although propeptide cleavage is clearly required for enzymatic activity, the protease(s) responsible for pro-GX sPLA2 activation have not been identified. We previously reported that GX sPLA2 negatively regulates adrenal glucocorticoid production, likely by suppressing liver X receptor-mediated activation of steroidogenic acute regulatory protein expression. In this study, using a FLAG epitope-tagged pro-GX sPLA2 expression construct (FLAG-pro-GX sPLA2), we determined that adrenocorticotropic hormone (ACTH) enhanced FLAG-pro-GX sPLA2 processing and phospholipase activity secreted by Y1 adrenal cells. ACTH increased the expression of furin and PCSK6, but not other members of the PC family, in Y1 cells. Overexpression of furin and PCSK6 in HEK 293 cells significantly enhanced FLAG-pro-GX sPLA2 processing, whereas siRNA-mediated knockdown of both PCs almost completely abolished FLAG-pro-GX sPLA2processing in Y1 cells. Expression of either furin or PCSK6 enhanced the ability of GX sPLA2 to suppress liver X receptor reporter activity. The PC inhibitor decanoyl-Arg-Val-Lys-Arg-chloromethyl ketone significantly suppressed FLAG-pro-GX sPLA2 processing and sPLA2 activity in Y1 cells, and it significantly attenuated GX sPLA2-dependent inhibition of steroidogenic acute regulatory protein expression and progesterone production. These findings provide strong evidence that pro-GX sPLA2 is a substrate for furin and PCSK6 proteolytic processing and define a novel mechanism for regulating corticosteroid production in adrenal cells. [ABSTRACT FROM AUTHOR]

Published
2015
Full Text
View/download PDF

Catalog

Books, media, physical & digital resources
See catalog results