Please use this identifier to cite or link to this item: http://hdl.handle.net/2080/4276
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dc.contributor.authorNaik, Lincoln-
dc.contributor.authorPatel, Salina-
dc.contributor.authorKumar, Ashish-
dc.contributor.authorGhosh, Abhirupa-
dc.contributor.authorMishra, Abtar-
dc.contributor.authorDas, Mousmi-
dc.contributor.authorNayak, Dev Kiran-
dc.contributor.authorSaha, Sudipto-
dc.contributor.authorMishra, Amit-
dc.contributor.authorSingh, Ramandeep-
dc.contributor.authorBehura, Assirbad-
dc.contributor.authorDhiman, Rohan-
dc.date.accessioned2024-01-09T11:30:29Z-
dc.date.available2024-01-09T11:30:29Z-
dc.date.issued2023-12-
dc.identifier.citation92nd Annual Meet of the Society of Biological Chemists(SBC) BITS Pilani, 18-20th Dec 2023en_US
dc.identifier.urihttp://hdl.handle.net/2080/4276-
dc.descriptionCopyright belongs to proceeding publisheren_US
dc.description.abstractThe 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.subjectTHP-1 cellsen_US
dc.subjectROS-dependenten_US
dc.titleRegulation 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+ Pathwayen_US
dc.typePresentationen_US
Appears in Collections:Conference Papers

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