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http://hdl.handle.net/2080/4276
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DC Field | Value | Language |
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dc.contributor.author | Naik, Lincoln | - |
dc.contributor.author | Patel, Salina | - |
dc.contributor.author | Kumar, Ashish | - |
dc.contributor.author | Ghosh, Abhirupa | - |
dc.contributor.author | Mishra, Abtar | - |
dc.contributor.author | Das, Mousmi | - |
dc.contributor.author | Nayak, Dev Kiran | - |
dc.contributor.author | Saha, Sudipto | - |
dc.contributor.author | Mishra, Amit | - |
dc.contributor.author | Singh, Ramandeep | - |
dc.contributor.author | Behura, Assirbad | - |
dc.contributor.author | Dhiman, Rohan | - |
dc.date.accessioned | 2024-01-09T11:30:29Z | - |
dc.date.available | 2024-01-09T11:30:29Z | - |
dc.date.issued | 2023-12 | - |
dc.identifier.citation | 92nd Annual Meet of the Society of Biological Chemists(SBC) BITS Pilani, 18-20th Dec 2023 | en_US |
dc.identifier.uri | http://hdl.handle.net/2080/4276 | - |
dc.description | Copyright belongs to proceeding publisher | en_US |
dc.description.abstract | The emergence of drug-resistant tuberculosis (TB) has emerged as a global public health crisis. Therefore, new and innovative therapeutic options like host-directed therapies (HDTs) through novel modulators are urgently required to overcome the challenges associated with TB. In this line, phenotypic screening from the LOPAC library identified 4-(Benzyloxy)phenol as a potent inhibitor against Mycobacterium bovis BCG growth in THP-1 cells. Further, the underlying mechanism behind the antimycobacterial role of 4-(Benzyloxy)phenol was delineated. It was observed that 4-(Benzyloxy)phenol activates p53 expression by hindering its association with KDM1A. Increased ROS, intracellular Ca 2+ and fusion of phagosome containing bacteria with the lysosome were also observed upon 4-(Benzyloxy)phenol treatment. Abrogation of the decreased intracellular mycobacterial load in the presence of specific inhibitors of intracellular ROS, Ca 2+ levels and phagosome-lysosome fusion like NAC, BAPTA-AM, and W7, respectively, pinpointed the physiological relevance of this mechanism in 4-(Benzyloxy)phenol treated cells. Experiments involving NAC and BAPTA-AM pre-treatment also suggested that ROS regulates the fusion of phagosome and lysosome through intracellular Ca 2+ levels in the treated cells. Pre-treatment experiments with the inhibitor of p53, Pifithrin-α, and its effect in augmenting mycobacterial survival substantiated the overall regulation of this pathway. Taken together, these findings demonstrate that 4- (Benzyloxy)phenol exerts its antimycobacterial effect by regulating p53-mediated intracellular Ca 2+ release through ROS production that induces phagosome-lysosome fusion. | en_US |
dc.subject | THP-1 cells | en_US |
dc.subject | ROS-dependent | en_US |
dc.title | Regulation of P53 Exhibits Anti Mycobacterial Role by Regulating Phagosome Lysosome Fusion in 4-(Benzyloxy) Phenol Treated THP-1 Cells Through ROS-dependent Intracellular Ca 2+ Pathway | en_US |
dc.type | Presentation | en_US |
Appears in Collections: | Conference Papers |
Files in This Item:
File | Description | Size | Format | |
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2023_SBC_SPatel_SIRT1-FOXO3.pdf | 1.1 MB | Adobe PDF | View/Open Request a copy |
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