Principal Investigator- Dr. Arnab Mukhopadhyay https://dspace.nii.res.in//https://dspace.nii.res.in/handle/123456789/36 2026-04-14T15:33:39Z 2026-04-14T15:33:39Z Sarkar, Gautam Chandra Rautela, Umanshi Goyala, Anita Datta, Sudeshna Anand, Nikhita Singh, Anupama Singh, Prachi Chamoli, Manish Mukhopadhyay, Arnab https://dspace.nii.res.in//https://dspace.nii.res.in/handle/123456789/1557 2025-12-05T12:48:19Z 2023-01-01T00:00:00Z

Title: DNA damage signals from somatic uterine tissue arrest oogenesis through activated DAF-16 Authors: Sarkar, Gautam Chandra; Rautela, Umanshi; Goyala, Anita; Datta, Sudeshna; Anand, Nikhita; Singh, Anupama; Singh, Prachi; Chamoli, Manish; Mukhopadhyay, Arnab Abstract: Germ line integrity is crucial for progeny fitness. Organisms deploy the DNA damage response (DDR) signaling to protect the germ line from genotoxic stress, facilitating the cell-cycle arrest of germ cells and DNA repair or their apoptosis. Cell-autonomous regulation of germ line quality in response to DNA damage is well studied; however, how quality is enforced cell non-autonomously on sensing somatic DNA damage is less known. Using Caenorhabditis elegans, we show that DDR disruption, only in the uterus, when insulin/IGF-1 signaling (IIS) is low, arrests oogenesis in the pachytene stage of meiosis I, in a FOXO/DAF-16 transcription factor-dependent manner. Without FOXO/DAF-16, germ cells of the IIS mutant escape the arrest to produce poor-quality oocytes, showing that the transcription factor imposes strict quality control during low IIS. Activated FOXO/DAF-16 senses DDR perturbations during low IIS to lower ERK/MPK-1 signaling below a threshold to promote germ line arrest. Altogether, we elucidate a new surveillance role for activated FOXO/DAF-16 that ensures optimal germ cell quality and progeny fitness in response to somatic DNA damage.

2023-01-01T00:00:00Z Mukhopadhyay, Arnab Alam, Maroof Bai, Shakuntala Dandawate, Monica Kumari, Neeta Gupta, Sonu Agrawal, Usha Nagarajan, Perumal Reddy, Dumbala Srinivasa Kulkarni, Mahesh J Garg, Amit https://dspace.nii.res.in//https://dspace.nii.res.in/handle/123456789/1484 2025-12-05T12:41:52Z 2023-01-01T00:00:00Z

Title: Protective Effects of Rifampicin and Its Analog Rifampicin Quinone in a Mouse Model of Obesity-Induced Type 2 Diabetes Authors: Mukhopadhyay, Arnab; Alam, Maroof; Bai, Shakuntala; Dandawate, Monica; Kumari, Neeta; Gupta, Sonu; Agrawal, Usha; Nagarajan, Perumal; Reddy, Dumbala Srinivasa; Kulkarni, Mahesh J; Garg, Amit Abstract: Advanced glycation end-products (AGEs) form when glucose reacts non-enzymatically with proteins, leading to abnormal protein function, oxidative stress, and inflammation. AGEs are associated with aging and age-related diseases; their formation is aggravated during diabetes. Therefore, drugs preventing AGE formation can potentially treat diabetic complications, positively affecting health. Earlier, we demonstrated that rifampicin and its analogs have potent anti-glycating activities and increase the life span of Caenorhabditis elegans. This study aimed to investigate the effects of rifampicin during hyperglycemia in C. elegans and in a mouse model of obesity-induced type 2 diabetes. The effects of rifampicin were assessed by determining the life span of C. elegans cultured in the presence of glucose and by measuring HbA1c, AGE levels, and glucose excursions in the diabetic mouse model. Our results show that rifampicin protects C. elegans from glucose-induced toxicity and increases life span. In mice, rifampicin reduces HbA1c and AGEs, improves insulin sensitivity, and reduces indications of diabetic nephropathy without inducing hepatotoxicity. Rifampicin quinone, an analog with lower anti-microbial activity, also reduces HbA1c levels, improves glucose homeostasis and insulin sensitivity, and lowers indications of diabetic nephropathy, without adversely affecting the liver of the diabetic mice. Altogether, our results indicate that rifampicin and its analog have protective roles during diabetes without inflicting hepatic damage and may potentially be considered for repositioning to treat hyperglycemia-related complications in patients.

2023-01-01T00:00:00Z Mukhopadhyay, Arnab https://dspace.nii.res.in//https://dspace.nii.res.in/handle/123456789/1344 2025-12-05T12:47:02Z 2016-01-01T00:00:00Z

Title: Oxidative Homeostasis Regulates the Response to Reductive Endoplasmic Reticulum Stress through Translation Control Authors: Mukhopadhyay, Arnab Abstract: Reductive stress leads to the loss of disulfide bond formation and induces the unfolded protein response of the endoplasmic reticulum (UPR(ER)), necessary to regain proteostasis in the compartment. Here we show that peroxide accumulation during reductive stress attenuates UPR(ER) amplitude by altering translation without any discernible effect on transcription. Through a comprehensive genetic screen in Saccharomyces cerevisiae, we identify modulators of reductive stress-induced UPR(ER) and demonstrate that oxidative quality control (OQC) genes modulate this cellular response in the presence of chronic but not acute reductive stress. Using a combination of microarray and relative quantitative proteomics, we uncover a non-canonical translation attenuation mechanism that acts in a bipartite manner to selectively downregulate highly expressed proteins, decoupling the cell's transcriptional and translational response during reductive ER stress. Finally, we demonstrate that PERK, a canonical translation attenuator in higher eukaryotes, helps in bypassing a ROS-dependent, non-canonical mode of translation attenuation.

2016-01-01T00:00:00Z Mukhopadhyay, Arnab Chamoli, Manish Goyala, Anita Tabrez, Syed Shamsh Siddiqui, Atif Ahmed Singh, Anupama Antebi, Adam Lithgow, Gordon J Watts, Jennifer L https://dspace.nii.res.in//https://dspace.nii.res.in/handle/123456789/1288 2025-12-05T12:44:41Z 2020-01-01T00:00:00Z

Title: Polyunsaturated fatty acids and p38-MAPK link metabolic reprogramming to cytoprotective gene expression during dietary restriction Authors: Mukhopadhyay, Arnab; Chamoli, Manish; Goyala, Anita; Tabrez, Syed Shamsh; Siddiqui, Atif Ahmed; Singh, Anupama; Antebi, Adam; Lithgow, Gordon J; Watts, Jennifer L Abstract: The metabolic state of an organism instructs gene expression modalities, leading to changes in complex life history traits, such as longevity. Dietary restriction (DR), which positively affects health and life span across species, leads to metabolic reprogramming that enhances utilisation of fatty acids for energy generation. One direct consequence of this metabolic shift is the upregulation of cytoprotective (CyTP) genes categorized in the Gene Ontology (GO) term of "Xenobiotic Detoxification Program" (XDP). How an organism senses metabolic changes during nutritional stress to alter gene expression programs is less known. Here, using a genetic model of DR, we show that the levels of polyunsaturated fatty acids (PUFAs), especially linoleic acid (LA) and eicosapentaenoic acid (EPA), are increased following DR and these PUFAs are able to activate the CyTP genes. This activation of CyTP genes is mediated by the conserved p38 mitogen-activated protein kinase (p38-MAPK) pathway. Consequently, genes of the PUFA biosynthesis and p38-MAPK pathway are required for multiple paradigms of DR-mediated longevity, suggesting conservation of mechanism. Thus, our study shows that PUFAs and p38-MAPK pathway function downstream of DR to help communicate the metabolic state of an organism to regulate expression of CyTP genes, ensuring extended life span.

2020-01-01T00:00:00Z