Biology subjects

Mahajan, N.

Publications and source records attributed to Mahajan, N..

3 recordsLinked to original sources

bioRxiv2021

Mucin-mimetic action of capsaicin improves high fat diet-induced gut barrier dysfunction in mice colon

The gut barrier - including tight junction proteins and mucus layers, is the first line of defense against physical, chemical, or pathogenic incursions. This barrier is compromised in various health disorders. Capsaicin, a dietary agonist of Transient receptor potential vanilloid 1 (TRPV1) channel, is reported to alleviate the complications of obesity. While its mode of action is well established to enhance energy expenditure, metabolism and prevent dysbiosis, the more local effects on the host gut - particularly the gut barrier and mucus system remain elusive. We employed a diet-induced obesity model to investigate the effect of capsaicin on the gut barrier and mucus production and to understand the involvement of mucus, bacteria, and TRPV1 in these phenomena. Mucin feeding reflected most of the effects produced by capsaicin, indicating that mucus modulation by capsaicin plays a crucial role in its anti-obesity effects. Capsaicin, bacteria and the host mucus system seem to act in a cyclic cascade involving TRPV1, which can be activated by capsaicin and various bacteria. These findings provide new insight into the role of TRPV1 in maintaining a healthy gut environment. HIGHLIGHTSO_LIExogenous mucin feeding produced anti-obesity effects similar to capsaicin in mice. C_LIO_LIMucin and capsaicin improved TJP expression, intestinal permeability and gut microbial diversity. C_LIO_LICapsaicin modulated bacterial diversity in vitro, independently of the host. C_LIO_LIProbiotic bacteria and butyrate activated TRPV1 in transfected HEK cells. C_LIO_LIAnti-obesity action of capsaicin is not exclusive to TRPV1 agonism. C_LIO_LICapsaicins action as colonic mucus secretagogue - plays a crucial part in its anti-obesity benefits. C_LI

pharmacology and toxicology↗

bioRxiv2021

Proximity-dependent biotinylation to elucidate the interactome of TNK2 non-receptor tyrosine kinase

Non-receptor tyrosine kinases represent an important class of signaling molecules which are involved in driving diverse cellular pathways. Although, the large majority have been well-studied in terms of their protein-binding partners, the interactomes of some of the key non-receptor tyrosine kinases such as TNK2 (also known as activated Cdc42-associated kinase 1 or ACK1) have not been systematically investigated. Aberrant expression and hyperphosphorylation of TNK2 has been implicated in a number of cancers. However, the exact proteins and cellular events that mediate phenotypic changes downstream of TNK2 are unclear. Biological systems that employ proximity-dependent biotinylation methods, such as BioID, are being increasingly used to map protein-protein interactions as they provide increased sensitivity in discovering interaction partners. In this study, we employed BioID coupled to the biotinylation site identification technology (BioSITe) method that we recently developed to perform molecular mapping of intracellular proteins associated with TNK2. We also employed stable isotope labeling with amino acids in cell culture (SILAC) to quantitatively explore the interactome of TNK2. By performing a controlled comparative analysis between full-length TNK2 and its truncated counterpart, we were not only able to confidently identify site-level biotinylation of previously well-established TNK2 binders and substrates such as NCK1, NCK2, CTTN, STAT3, but also discover several novel TNK2 interacting partners. We validated TNK2 interaction with one of the novel TNK2 interacting protein, clathrin interactor 1 (CLINT1), using immunoblot analysis. Overall, this work reveals the power of the BioSITe method coupled to BioID and highlights several molecules that warrant further exploration to assess their functional significance in TNK2-mediated signaling.

cancer biology↗

bioRxiv2020

Role of TRPV1 in colonic mucin production and gut microbiota profile

PURPOSEThis study focuses on exploring the role of sensory cation channel Transient Receptor Potential channel subfamily Vanilloid 1 (TRPV1) in gut health, specifically mucus secretion and microflora profile in gut. METHODS AND RESULTSWe employed resiniferatoxin (ultrapotent TRPV1 agonist) induced chemo-denervation model in rats and studied the effects of TRPV1 ablation on gut mucus secretion patterns. Histological and transcriptional analysis showed substantial decrease in mucus production as well as in expression of genes involved in goblet cells differentiation, mucin production and glycosylation. 16S metagenome analysis revealed changes in abundance of various gut bacteria, including decrease in beneficial bacteria like Lactobacillus spp and Clostridia spp. Also, TRPV1 ablation significantly decreased the levels of short chain fatty acids, i.e. acetate and butyrate. CONCLUSIONThe present study provides first evidence that systemic TRPV1 ablation leads to impairment in mucus secretion and causes dysbiosis in gut. Further, it suggests to address mucin production and gut microbiota related adverse effects during the development of TRPV1 antagonism/ablation-based therapeutic and preventive strategies.

physiology↗