Meeting the meat: delineating the molecular machinery of muscle development

( Arif Tasleem Jan ),( Eun Ju Lee ),( Sarafraz Ahmad ),( Inho Choi ) 한국동물자원과학회(구 한국축산학회) 2016 한국축산학회지 Vol.58 No.5

Muscle, studied mostly with respect to meat production, represents one of the largest protein reservoirs of the body. As gene expression profiling holds credibility to deal with the increasing demand of food from animal sources, excessive loss due to myopathies and other muscular dystrophies was found detrimental as it aggravates diseases that result in increased morbidity and mortality. Holding key point towards improving the developmental program of muscle in meat producing animals, elucidating the underlying mechanisms of the associated pathways in livestock animals is believed to open up new avenues towards enhancing the lean tissue deposition. To this end, identification of vital candidate genes having no known function in myogenesis, is believed to increase the current understanding of the physiological processes going on in the skeletal muscle tissue. Taking consequences of gene expression changes into account, knowledge of the pathways associated with their activation and as such up-regulation seems critical for the overall muscle homeostasis. Having important implications on livestock production, a thorough understanding of postnatal muscle development seems a timely step to fulfil the growing need of ever increasing populations of the world.

Analysis for the presence of determinants involved in the transport of mercury across bacterial membrane from polluted water bodies of India

Jan, Arif Tasleem,Azam, Mudsser,Choi, Inho,Ali, Arif,Haq, Qazi Mohd. Rizwanul Elsevier 2016 Brazilian journal of microbiology Vol.47 No.1

<P>Mercury, which is ubiquitous and recalcitrant to biodegradation processes, threatens human health by escaping to the environment via various natural and anthropogenic activities. Non-biodegradability of mercury pollutants has necessitated the development and implementation of economic alternatives with promising potential to remove metals from the environment. Enhancement of microbial based remediation strategies through genetic engineering approaches provides one such alternative with a promising future. In this study, bacterial isolates inhabiting polluted sites were screened for tolerance to varying concentrations of mercuric chloride. Following identification, several <I>Pseudomonas</I> and <I>Klebsiella</I> species were found to exhibit the highest tolerance to both organic and inorganic mercury. Screened bacterial isolates were examined for their genetic make-up in terms of the presence of genes (<I>mer</I>P and <I>mer</I>T) involved in the transport of mercury across the membrane either alone or in combination to deal with the toxic mercury. Gene sequence analysis revealed that the <I>mer</I>P gene showed 86–99% homology, while the <I>mer</I>T gene showed >98% homology with previously reported sequences. By exploring the genes involved in imparting metal resistance to bacteria, this study will serve to highlight the credentials that are particularly advantageous for their practical application to remediation of mercury from the environment.</P>

Perspective Insights of Exosomes in Neurodegenerative Diseases: A Critical Appraisal

Jan, Arif Tasleem,Malik, Mudasir A.,Rahman, Safikur,Yeo, Hye R.,Lee, Eun J.,Abdullah, Tasduq S.,Choi, Inho Frontiers Media S.A. 2017 FRONTIERS IN AGING NEUROSCIENCE Vol.9 No.-

<P>Exosomes are small membranous entities of endocytic origin. Their production by a wide variety of cells in eukaryotes implicates their roles in the execution of essential processes, especially cellular communication. Exosomes are secreted under both physiological and pathophysiological conditions, and their actions on neighboring and distant cells lead to the modulations of cellular behaviors. They also assist in the delivery of disease causing entities, such as prions, α-syn, and tau, and thus, facilitate spread to non-effected regions and accelerate the progressions of neurodegenerative diseases. The characterization of exosomes, provides information on aberrant processes, and thus, exosome analysis has many clinical applications. Because they are associated with the transport of different cellular entities across the blood-brain barrier (BBB), exosomes might be useful for delivering drugs and other therapeutic molecules to brain. Herein, we review roles played by exosomes in different neurodegenerative diseases, and the possibilities of using them as diagnostic biomarkers of disease progression, drug delivery vehicles and in gene therapy.</P>

Perspective Insights into Disease Progression, Diagnostics, and Therapeutic Approaches in Alzheimer's Disease: A Judicious Update

Jan, Arif Tasleem,Azam, Mudsser,Rahman, Safikur,Almigeiti, Angham M. S.,Choi, Duk Hwan,Lee, Eun Ju,Haq, Qazi Mohd Rizwanul,Choi, Inho Frontiers Media S.A. 2017 FRONTIERS IN AGING NEUROSCIENCE Vol.9 No.-

<P>Alzheimer's disease (AD) is a neurodegenerative disorder characterized by the progressive accumulation of β-amyloid fibrils and abnormal tau proteins in and outside of neurons. Representing a common form of dementia, aggravation of AD with age increases the morbidity rate among the elderly. Although, mutations in the ApoE4 act as potent risk factors for sporadic AD, familial AD arises through malfunctioning of APP, PSEN-1, and−2 genes. AD progresses through accumulation of amyloid plaques (Aβ) and neurofibrillary tangles (NFTs) in brain, which interfere with neuronal communication. Cellular stress that arises through mitochondrial dysfunction, endoplasmic reticulum malfunction, and autophagy contributes significantly to the pathogenesis of AD. With high accuracy in disease diagnostics, Aβ deposition and phosphorylated tau (p-tau) are useful core biomarkers in the cerebrospinal fluid (CSF) of AD patients. Although five drugs are approved for treatment in AD, their failures in achieving complete disease cure has shifted studies toward a series of molecules capable of acting against Aβ and p-tau. Failure of biologics or compounds to cross the blood-brain barrier (BBB) in most cases advocates development of an efficient drug delivery system. Though liposomes and polymeric nanoparticles are widely adopted for drug delivery modules, their use in delivering drugs across the BBB has been overtaken by exosomes, owing to their promising results in reducing disease progression.</P>

Entanglement of UPR ^ER in Aging Driven Neurodegenerative Diseases

Rahman, Safikur,Jan, Arif Tasleem,Ayyagari, Archana,Kim, Jiwoo,Kim, Jihoe,Minakshi, Rinki Frontiers Media S.A. 2017 FRONTIERS IN AGING NEUROSCIENCE Vol.9 No.-

<P>The endoplasmic reticulum (ER) is an indispensable cellular organelle that remains highly active in neuronal cells. The ER bears the load of maintaining protein homeostasis in the cellular network by managing the folding of incoming nascent peptides; however, the stress imposed by physiological/environmental factors can cause ER dysfunctions that lead to the activation of ER unfolded protein response (UPR<SUP>ER</SUP>). Aging leads to deterioration of several cellular pathways and therefore weakening of the UPR<SUP>ER</SUP>. The decline in functioning of the UPR<SUP>ER</SUP> during aging results in accumulation of misfolded proteins that becomes intracellular inclusions in neuronal cells, resulting in toxicity manifested as neurodegenerative diseases. With ascension in cases of neurodegenerative diseases, understanding the enigma behind aging driven UPR<SUP>ER</SUP> dysfunction may lead to possible treatments.</P>

Implications of aging and the endoplasmic reticulum unfolded protein response on the molecular modality of breast cancer

Minakshi, Rinki,Rahman, Safikur,Jan, Arif Tasleem,Archana, Ayyagari,Kim, Jihoe Nature Publishing Group 2017 Experimental and molecular medicine Vol.49 No.11

<P>The endoplasmic reticulum (ER) is an important subcellular organelle that is involved in numerous activities required to achieve and maintain functional proteins in addition to its role in the biosynthesis of lipids and as a repository of intracellular Ca<SUP>2+</SUP>. The inability of the ER to cope with protein folding beyond its capacity causes disturbances that evoke ER stress. Cells possess molecular mechanisms aimed at clearing unwanted cargo from the ER lumen as an adaptive response, but failing to do so navigates the system towards cell death. This systemic approach is called the unfolded protein response. Aging insults cells through various perturbations in homeostasis that involve curtailing ER function by mitigating the expression of its resident chaperones and enzymes. Here the unfolded protein response (UPR) cannot protect the cell due to the weakening of its protective arm, which exacerbates imbalanced homeostasis. Aging predisposed breast malignancy activates the UPR, but tumor cells maneuver the mechanistic details of the UPR, favoring tumorigenesis and thereby eliciting a treacherous condition. Tumor cells exploit UPR pathways via crosstalk involving various signaling cascades that usher tumor cells to immortality. This review aims to present a collection of data that can delineate the missing links of molecular signatures between aging and breast cancer.</P>

Implications of aging and the endoplasmic reticulum unfolded protein response on the molecular modality of breast cancer

Rinki Minakshi,Safikur Rahman,Arif Tasleem Jan,Ayyagari Archana,김지회 생화학분자생물학회 2017 Experimental and molecular medicine Vol.49 No.-

The endoplasmic reticulum (ER) is an important subcellular organelle that is involved in numerous activities required to achieve and maintain functional proteins in addition to its role in the biosynthesis of lipids and as a repository of intracellular Ca2+. The inability of the ER to cope with protein folding beyond its capacity causes disturbances that evoke ER stress. Cells possess molecular mechanisms aimed at clearing unwanted cargo from the ER lumen as an adaptive response, but failing to do so navigates the system towards cell death. This systemic approach is called the unfolded protein response. Aging insults cells through various perturbations in homeostasis that involve curtailing ER function by mitigating the expression of its resident chaperones and enzymes. Here the unfolded protein response (UPR) cannot protect the cell due to the weakening of its protective arm, which exacerbates imbalanced homeostasis. Aging predisposed breast malignancy activates the UPR, but tumor cells maneuver the mechanistic details of the UPR, favoring tumorigenesis and thereby eliciting a treacherous condition. Tumor cells exploit UPR pathways via crosstalk involving various signaling cascades that usher tumor cells to immortality. This review aims to present a collection of data that can delineate the missing links of molecular signatures between aging and breast cancer.

Fibromodulin: a master regulator of myostatin controlling progression of satellite cells through a myogenic program

Lee, Eun Ju,Jan, Arif Tasleem,Baig, Mohammad Hassan,Ashraf, Jalaluddin Mohammad,Nahm, Sang-Soep,Kim, Yong-Woon,Park, So-Young,Choi, Inho The Federation of American Societies for Experimen 2016 The FASEB Journal Vol.30 No.8

<P>Differentiation of muscle satellite cells (MSCs) involves interaction of the proteins present in the extracellular matrix (ECM) with MSCs to regulate their activity, and therefore phenotype. Herein, we report fibromodulin(FMOD), a member of the proteoglycan family participating in the assembly of ECM, as a novel regulator of myostatin (MSTN) during myoblast differentiation. In addition to having a pronounced effect on the expression of myogenic marker genes [myogenin (MYOG) and myosin light chain 2 (MYL2)], FMOD was found to maintain the transcriptional activity of MSTN. Moreover, coimmunoprecipitation and in silico studies performed to investigate the interaction of FMOD helped confirm that it antagonizes MSTN function by distorting its folding and preventing its binding to activin receptor type IIB. Furthermore, in vivo studies revealed that FMOD plays an active role in healing by increasing satellite cell recruitment to sites of injury. Together, these findings disclose a hitherto unrecognized regulatory role for FMOD in MSCs and highlight new mechanisms whereby FMOD circumvents the inhibitory effects of MSTN and triggers myoblast differentiation. These findings offer a basis for the design of novel MSTN inhibitors that promote muscle regeneration after injury or for the development of pharmaceutical agents for the treatment of different muscle atrophies.</P>

Physicochemical analysis of structural alteration and advanced glycation end products generation during glycation of H2A histone by 3-deoxyglucosone : GLYCATING POTENTIAL OF 3-DG WITH H2A HISTONE PROTEIN

Ashraf, Jalaluddin M.,Ahmad, Saheem,Rabbani, Gulam,Jan, Arif Tasleem,Lee, Eun Ju,Khan, Rizwan Hasan,Choi, Inho Wiley (John WileySons) 2014 IUBMB life Vol.66 No.10

<P>Advanced glycation end-products comprise a complex and heterogeneous group of compounds that have been implicated in diabetes-related complications. The importance of the Maillard reaction is depicted by the formation of reactive intermediate products known as α-oxoaldehydes, such as 3-deoxyglucosone (3-DG). This product has been found to be involved in accelerated vascular damage in diabetes. In the present study, calf thymus histone H2A was reacted with 3-DG, and the generation of advanced glycation end products was investigated by determining the degree of side chain modifications (lysine and arginine residues), Amadori products, carbonyl content, N(ε) -carboxymethyl lysine, and pentosidine using various physicochemical techniques. Moreover, fluorescence, absorbance as well as structural characteristics of glycated-H2A were comprehensively investigated. Overall, this study demonstrates structural perturbation, formation of different intermediates, and AGEs that are believed to hamper the normal functioning of H2A histone, compromising the integrity of chromatin structures and function in secondary complications of diabetes.</P>

Transthyretin: A Transporter Protein Essential for Proliferation of Myoblast in the Myogenic Program

Lee, Eun Ju,Pokharel, Smritee,Jan, Arif Tasleem,Huh, Soyeon,Galope, Richelle,Lim, Jeong Ho,Lee, Dong-Mok,Choi, Sung Wook,Nahm, Sang-Soep,Kim, Yong-Woon,Park, So-Young,Choi, Inho MDPI 2017 INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES Vol.18 No.1

<P>Irregularities in the cellular uptake of thyroid hormones significantly affect muscle development and regeneration. Herein, we report indispensable role of transthyretin (TTR) in maintaining cellular thyroxine level. TTR was found to enhance recruitment of muscle satellite cells to the site of injury, thereby regulating muscle regeneration. Fluorescence-activated cell sorting (FACS) and immunofluorescence analysis of TTR<SUB>wt</SUB> (TTR wild type) and TTR<SUB>kd</SUB> (TTR knock-down) cells revealed that TTR controlled cell cycle progression by affecting the expression of Cyclin A2. Deiodinase 2 (D2) mediated increases in triiodothyronine levels were found to regulate the expression of myogenic marker, myogenin (MYOG). Moreover, use of a coumarin derivative (CD) revealed a significant reduction in cellular thyroxine, thereby indicating that TTR play a role in the transport of thyroxine. Taken together, these findings suggest that TTR mediated transport of thyroxine represents a survival mechanism necessary for the myogenic program. The results of this study will be highly useful to the strategic development of novel therapeutics to combat muscular dystrophies.</P>