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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 |
Authors: | Naik, Lincoln Ghosh, Abhirupa Saha, Sudipto Singh, Ramandeep Dhiman, Rohan |
Keywords: | tuberculosis (TB) THP-1 4-(Benzyloxy)phenol |
Issue Date: | Mar-2023 |
Citation: | Three-day Symposium on Towards End TB: Achievements, Challenges and Future Directions, THSTI, Faridabad, 23rd-25th March 2023 |
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, Ca2+ 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 Ca2+ 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 Ca2+ release through ROS production that induces phagosome-lysosome fusion |
Description: | Copyright belongs to proceeding publisher |
URI: | http://hdl.handle.net/2080/4004 |
Appears in Collections: | Conference Papers |
Files in This Item:
File | Description | Size | Format | |
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2023_TBConf_LNaik_Regulation.pdf | Poster | 1.65 MB | Adobe PDF | View/Open |
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