A5091363709- Autophagy in Disease and Therapy
- Nerve injury and regeneration
- Sirtuins and Resveratrol in Medicine
- Pain Mechanisms and Treatments
- Cannabis and Cannabinoid Research
- Genetics, Aging, and Longevity in Model Organisms
- Advanced Fiber Optic Sensors
- Pregnancy and preeclampsia studies
- Cardiac, Anesthesia and Surgical Outcomes
- Smart Materials for Construction
- Cancer-related Molecular Pathways
- Ultrasonics and Acoustic Wave Propagation
- Medicinal Plants and Neuroprotection
- Airway Management and Intubation Techniques
- Genomics, phytochemicals, and oxidative stress
- Tracheal and airway disorders
- Vitamin C and Antioxidants Research
- Synthesis and biological activity
- Epigenetics and DNA Methylation
- Adenosine and Purinergic Signaling
- Anesthesia and Pain Management
- Respiratory and Cough-Related Research
- RNA regulation and disease
- Health and Well-being Studies
- Hepatitis C virus research
Jinnah Postgraduate Medical Center
2019-2023
University of Sargodha
2015-2023
Centre de Recherche des Cordeliers
2014-2020
Inserm
2010-2020
Sorbonne Université
2018-2020
Université Paris Cité
2014-2020
Emory University
2016-2020
Délégation Paris 5
2014-2018
Sorbonne Paris Cité
2014-2018
Institut Gustave Roussy
2010-2018
Caloric restriction and autophagy-inducing pharmacological agents can prolong lifespan in model organisms including mice, flies, nematodes. In this study, we show that transgenic expression of Sirtuin-1 induces autophagy human cells vitro Caenorhabditis elegans vivo. The knockdown or knockout prevented the induction by resveratrol nutrient deprivation as well dietary C. elegans. Conversely, was not required for rapamycin p53 inhibition, neither nor inhibition enhanced vulnerability to...
Autophagy protects organelles, cells, and organisms against several stress conditions. Induction of autophagy by resveratrol requires the nicotinamide adenine dinucleotide–dependent deacetylase sirtuin 1 (SIRT1). In this paper, we show that acetylase inhibitor spermidine stimulates independent SIRT1 in human yeast cells as well nematodes. Although ignite through distinct mechanisms, these compounds stimulate convergent pathways culminate concordant modifications acetylproteome. Both agents...
The oncosuppressor protein p53 regulates autophagy in a dual fashion. pool of cytoplasmic represses transcription-independent fashion, while the nuclear stimulates through transactivation specific genes. Here we report discovery that Sestrin2, novel target gene, is involved induction autophagy. Depletion Sestrin2 by RNA interference reduced level panel p53-sufficient human cancer cell lines responding to distinct inducers. In quantitative terms, depletion was as efficient preventing Dram,...
The age-associated deterioration in cellular and organismal functions associates with dysregulation of nutrient-sensing pathways disabled autophagy. reactivation autophagic flux may prevent or ameliorate age-related metabolic dysfunctions. Non-toxic compounds endowed the capacity to reduce overall levels protein acetylation induce autophagy have been categorized as caloric restriction mimetics (CRMs). Here, we show that aspirin its active metabolite salicylate by virtue their inhibit...
Background and Aims The proinflammatory cytokine IL‐1β has been implicated in the pathophysiology of nonalcoholic alcoholic steatohepatitis. How promotes liver injury these diseases is unclear, as no receptor‐linked death pathway identified. Autophagy functions hepatocyte resistance to death, findings decreased hepatic autophagy many suggest a role for impaired disease pathogenesis. Recent that blocks mouse from lipopolysaccharide led an examination autophagy’s function hepatotoxicity...
It is well-established that the activation of inhibitor NFκB (IκBα) kinase (IKK) complex required for autophagy induction by multiple stimuli. Here, we show in autophagy-competent mouse embryonic fibroblasts (MEFs), distinct autophagic triggers, including starvation, mTOR inhibition with rapamycin and p53 cyclic pifithrin α lead to IKK, followed phosphorylation-dependent degradation IκBα nuclear translocation NFκB. Remarkably, signaling pathway was blocked MEFs lacking either essential genes...
Resveratrol is a polyphenol contained in red wine that has been amply investigated for its beneficial effects on organismal metabolism, particular the context of so-called "French paradox," i.e., relatively low incidence coronary heart disease exhibited by population with high dietary intake cholesterol and saturated fats. At least part effect resveratrol human health stems from capacity to promote autophagy activating NAD-dependent deacetylase sirtuin 1. However, concentration found...
Epidemiological studies and clinical trials revealed that chronic consumption coffee is associated with the inhibition of several metabolic diseases as well reduction in overall cause-specific mortality. We show both natural decaffeinated brands similarly rapidly trigger autophagy mice. One to 4 h after consumption, we observed an increase autophagic flux all investigated organs (liver, muscle, heart) vivo, indicated by increased lipidation LC3B abundance substrate sequestosome 1...
A chemical screen designed to identify novel inducers of autophagy led the discovery that signal transducer and activator transcription 3 (STAT3) inhibitors can potently stimulate autophagic flux. Although STAT3 is best known as a pro-inflammatory oncogenic factor, mechanistic analyses revealed regulated by cytoplasmic, not nuclear, pool STAT3. Cytoplasmic normally interacts with eukaryotic translation initiation factor 2, subunit 1α, 35kDa (EIF2S1/eIF2α) kinase 2/protein kinase,...
The satiety hormone leptin plays a cardinal role in the pathophysiology of obesity and diabetes. Here, we show that pharmacological autophagy inducers like rapamycin, spermidine resveratrol can reduce concentrations serum mice genetic inactivation leptin/leptin receptor system leads to an increase peripheral tissues including skeletal muscle, heart liver. Paradoxically, intravenous or intraperitoneal administration recombinant protein also induced these tissues. Moreover, stimulated...
During sepsis, bacterial products, particularly LPS, trigger injury in organs such as the liver. This common condition remains largely untreatable, part due to a lack of understanding how high concentrations LPS cause cellular injury. In liver, lysosomal degradative pathway autophagy performs essential hepatoprotective functions and is induced by LPS. We, therefore, examined whether hepatocyte protects against liver from septic levels Mice with an inducible hepatocyte-specific knockout...
Peripheral nerve injuries are one of those complex medical conditions for which a highly effective first-line treatment is currently missing. The use natural compound as medicines to treat various disorders has long history. Our previous research explored that crude
Autophagic flux can be measured by determining the declining abundance of autophagic substrates such as sequestosome 1 (SQSTM1, better known p62), which is sequestered in autophagosomes upon its direct interaction with LC3. However, total amount p62 results from two opposed processes, namely synthesis (which modulated some cellular stressors including autophagy inducers) and degradation. To avoid this problem, we generated a stable cell line expressing chimeric protein composed HaloTag (®)...
General (macro)autophagy and the activation of NFκB constitute prominent responses to a large array intracellular extracellular stress conditions. The depletion any three subunits inhibitor (IκB) kinase (IKKα, IKKβ, IKKγ/NEMO), each which is essential for canonical pathway, limits autophagy induction by physiological or pharmacological triggers, while constitutive active IKK suffice stimulate autophagy. usually relies on TGFβ-activated 1 (TAK1), also necessary optimal in multiple settings....
The acetylase inhibitor, spermidine and the deacetylase activator, resveratrol, both induce autophagy prolong life span of model organism Caenorhabditis elegans in an autophagydependent fashion. Based on these premises, we investigated differences similarities resveratrol-induced autophagy. sirtuin 1 (SIRT1) its orthologs are required for induction by resveratrol but dispensable stimulation human cells, Saccharomyces cerevisiae C. elegans. SIRT1 is also life-span extension spermidine. Mass...