Younis Hazari

A set of cellular response to counter any alteration in homeostasis of a cell originating at endoplasmic reticulum is collectively termed as unfolded protein response (UPR). It initially is adaptive in nature as to restore cellular normalcy failing in course often activates pro-apoptotic signaling pathway resulting in cell death. UPR has emerged as...

Autophagy is an evolutionarily ancient process whereby eukaryotic cells eliminate disposable or potentially dangerous cytoplasmic material, to support bioenergetic metabolism and adapt to stress. Accumulating evidence indicates that autophagy operates as a critical quality control mechanism for the maintenance of hepatic homeostasis in both parench...

Mitochondria-associated membranes (MAMs) are central microdomains that fine-tune bioenergetics by the local transfer of calcium from the endoplasmic reticulum to the mitochondrial matrix. Here, we report an unexpected function of the endoplasmic reticulum stress transducer IRE1α as a structural determinant of MAMs that controls mitochondrial calciu...

The obesity epidemic is accompanied by a worldwide burden of non-alcoholic fatty liver disease (NAFLD) that manifests from simple steatosis to non-alcoholic steatohepatitis (NASH), possibly evolving into hepatocellular carcinoma (HCC). Although much attention has been focused on NAFLD, its pathogenesis remains largely obscure. The hallmark of NAFLD...

Maintenance of endoplasmic reticulum (ER) proteostasis is controlled by a dynamic signaling network known as the unfolded protein response (UPR). IRE1α is a major UPR transducer, determining cell fate under ER stress. We used an interactome screening to unveil several regulators of the UPR, highlighting the ER chaperone Hsp47 as the major hit. Cell...

Alpha1-antitrypsin (α1AT) is an abundant serine-protease inhibitor in circulation. It has an important role in neutralizing the neutrophil elastase activity. Different pathogenic point mutations like Z(E342K)-α1AT have been implicated in the development of liver cirrhosis and Chronic Obstructive Pulmonary Disease (COPD), the latter being a cluster...

The molecular connections between homeostatic systems that maintain both genome integrity and proteostasis are poorly understood. Here we identify the selective activation of the unfolded protein response transducer IRE1α under genotoxic stress to modulate repair programs and sustain cell survival. DNA damage engages IRE1α signaling in the absence...

Purpose: Different mutations in coding and non-coding sequences of the SERPINA1 gene have been implicated in the pathogenesis of COPD. However, - 10T/C mutation in the hepatocyte-directed promoter region has not been associated with COPD pathogenesis so far. Here, we report an increased frequency of - 10C genotype that is associated with decreased...

Maintenance of endoplasmic reticulum (ER) proteostasis is controlled by a signalling network known as the unfolded protein response (UPR). Here, we identified filamin A as a major binding partner of the ER stress transducer IRE1α. Filamin A is an actin crosslinking factor involved in cytoskeleton remodelling. We show that IRE1α controls actin cytos...

α-Lactalbumin (α-La) gene is involved in milk production traits in dairy animals. The variability in milk production potentials of different animals have been attributed to the polymorphism existing within this gene. The study was carried out to detect polymorphism in PCR amplified DNA fragments encompassing to − 363 to + 80 of the α-La gene in 50...

The p70ΔCT104S6K is a 421 amino acid residue long truncated form of p70S6 kinase, with 104 aminoacids residues cleaved from the carboxyl terminal end of the original protein. The p70ΔCT104S6K wascloned in E. coli DH5α and successfully expressed in E. coli BL21 (DE3) strain. Western blot with rabbitpolyclonal anti-GST antibody was used to follow the...

Four alkaloid constituents: harmine, vasicine, vasicinone and harmaline were isolated and characterized from Peganum harmala roots. Harmine showed the best cytotoxicity with IC50 of 32, 106, 45, 33 and 61 μM against breast (HBL-100), lung (A549), colon (HT-29 & HCT-116) and cervical (HELA) cells respectively. The harmine analogs, synthesized via cl...

Alpha-1-antitrypsin (AAT) is an acute phase secretory glycoprotein that inhibits neutrophil proteases like elastase and is considered as the archetype of a family of structurally related serine protease inhibitors termed serpins. Serum AAT predominantly originates from liver and increases three to five fold during host response to tissue injury and...

Alpha1-antitrypsin (AAT) is one of the major circulating anti-protease whose levels in circulation are raised during excessive amount of proteases, especially neutrophil elastase (NE) released during the course of inflammation. Proteolytic attack of NE on peripheral organs, more exclusively on lung parenchyma has severe consequence that may precipi...

Aims: Osmolytes are small organic molecules which play significant role in maintaining functional homeostasis of proteins under extreme hostile stresses. Any imbalance to cell homeostasis leads to Endoplasmic Reticulum stress (ER-stress) to which a set of cellular responses both at transcriptional and translational level are initialed for restorat...

Fusobacterium nucleatum is an identified proinflammatory autochthonous bacterium implicated in human colorectal cancer. It is also abundantly found in patients suffering from chronic gut inflammation (inflammatory bowel disease), consequently contributing to the pathogenesis of colorectal cancer. Majority of the studies have reported that colorecta...