Publications by authors named "Mahboob Morshed"

15 Publications

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Sigmar1's Molecular, Cellular, and Biological Functions in Regulating Cellular Pathophysiology.

Front Physiol 2021 7;12:705575. Epub 2021 Jul 7.

Department of Molecular and Cellular Physiology, Louisiana State University Health Sciences Center-Shreveport, Shreveport, LA, United States.

The Sigma 1 receptor (Sigmar1) is a ubiquitously expressed multifunctional inter-organelle signaling chaperone protein playing a diverse role in cellular survival. Recessive mutation in Sigmar1 have been identified as a causative gene for neuronal and neuromuscular disorder. Since the discovery over 40 years ago, Sigmar1 has been shown to contribute to numerous cellular functions, including ion channel regulation, protein quality control, endoplasmic reticulum-mitochondrial communication, lipid metabolism, mitochondrial function, autophagy activation, and involved in cellular survival. Alterations in Sigmar1's subcellular localization, expression, and signaling has been implicated in the progression of a wide range of diseases, such as neurodegenerative diseases, ischemic brain injury, cardiovascular diseases, diabetic retinopathy, cancer, and drug addiction. The goal of this review is to summarize the current knowledge of Sigmar1 biology focusing the recent discoveries on Sigmar1's molecular, cellular, pathophysiological, and biological functions.
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http://dx.doi.org/10.3389/fphys.2021.705575DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8293995PMC
July 2021

Dysfunctional Mitochondrial Dynamic and Oxidative Phosphorylation Precedes Cardiac Dysfunction in R120G-αB-Crystallin-Induced Desmin-Related Cardiomyopathy.

J Am Heart Assoc 2020 12 19;9(23):e017195. Epub 2020 Nov 19.

Department of Pathology and Translational Pathobiology Louisiana State University Health Sciences Center Shreveport LA.

Background The mutated α-B-Crystallin (CryAB) mouse model of desmin-related myopathy (DRM) shows an age-dependent onset of pathologic cardiac remodeling and progression of heart failure. CryAB expression in cardiomyocytes affects the mitochondrial spatial organization within the myofibrils, but the molecular perturbation within the mitochondria in the relation of the overall course of the proteotoxic disease remains unclear. Methods and Results CryAB mice show an accumulation of electron-dense aggregates and myofibrillar degeneration associated with the development of cardiac dysfunction. Though extensive studies demonstrated that these altered ultrastructural changes cause cardiac contractility impairment, the molecular mechanism of cardiomyocyte death remains elusive. Here, we explore early pathological processes within the mitochondria contributing to the contractile dysfunction and determine the pathogenic basis for the heart failure observed in the CryAB mice. In the present study, we report that the CryAB mice transgenic hearts undergo altered mitochondrial dynamics associated with increased level of dynamin-related protein 1 and decreased level of optic atrophy type 1 as well as mitofusin 1 over the disease process. In association with these changes, an altered level of the components of mitochondrial oxidative phosphorylation and pyruvate dehydrogenase complex regulatory proteins occurs before the manifestation of pathologic adverse remodeling in the CryAB hearts. Mitochondria isolated from CryAB transgenic hearts without visible pathology show decreased electron transport chain complex activities and mitochondrial respiration. Taken together, we demonstrated the involvement of mitochondria in the pathologic remodeling and progression of DRM-associated cellular dysfunction. Conclusions Mitochondrial dysfunction in the form of altered mitochondrial dynamics, oxidative phosphorylation and pyruvate dehydrogenase complex proteins level, abnormal electron transport chain complex activities, and mitochondrial respiration are evident on the CryAB hearts before the onset of detectable pathologies and development of cardiac contractile dysfunction.
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http://dx.doi.org/10.1161/JAHA.120.017195DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7763772PMC
December 2020

Methamphetamine induces cardiomyopathy by Sigmar1 inhibition-dependent impairment of mitochondrial dynamics and function.

Commun Biol 2020 11 17;3(1):682. Epub 2020 Nov 17.

Department of Pathology and Translational Pathobiology, Louisiana State University Health Sciences Center-Shreveport, Shreveport, LA, 71103, USA.

Methamphetamine-associated cardiomyopathy is the leading cause of death linked with illicit drug use. Here we show that Sigmar1 is a therapeutic target for methamphetamine-associated cardiomyopathy and defined the molecular mechanisms using autopsy samples of human hearts, and a mouse model of "binge and crash" methamphetamine administration. Sigmar1 expression is significantly decreased in the hearts of human methamphetamine users and those of "binge and crash" methamphetamine-treated mice. The hearts of methamphetamine users also show signs of cardiomyopathy, including cellular injury, fibrosis, and enlargement of the heart. In addition, mice expose to "binge and crash" methamphetamine develop cardiac hypertrophy, fibrotic remodeling, and mitochondrial dysfunction leading to contractile dysfunction. Methamphetamine treatment inhibits Sigmar1, resulting in inactivation of the cAMP response element-binding protein (CREB), decreased expression of mitochondrial fission 1 protein (FIS1), and ultimately alteration of mitochondrial dynamics and function. Therefore, Sigmar1 is a viable therapeutic agent for protection against methamphetamine-associated cardiomyopathy.
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http://dx.doi.org/10.1038/s42003-020-01408-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7673131PMC
November 2020

Chemical Architecture of Block Copolymers Differentially Abrogate Cardiotoxicity and Maintain the Anticancer Efficacy of Doxorubicin.

Mol Pharm 2020 12 5;17(12):4676-4690. Epub 2020 Nov 5.

Department of Coatings and Polymeric Materials, North Dakota State University, Fargo, North Dakota 58108, United States.

The molecular architecture of pH-responsive amphiphilic block copolymers, their self-assembly behavior to form nanoparticles (NPs), and doxorubicin (DOX)-loading technique govern the extent of DOX-induced cardiotoxicity. We observed that the choice of pH-sensitive tertiary amines, surface charge, and DOX-loading techniques within the self-assembled NPs strongly influence the release and stimulation of DOX-induced cardiotoxicity in primary cardiomyocytes. However, covalent conjugation of DOX to a pH-sensitive nanocarrier through a "conditionally unstable amide" linkage (PCPY-cDOX; PC = polycarbonate and PY = 2-pyrrolidine-1-yl-ethyl-amine) significantly reduced the cardiotoxicity of DOX in cardiomyocytes as compared to noncovalently encapsulated DOX NPs (PCPY-eDOX). When these formulations were tested for drug release in serum-containing media, the PCPY-cDOX systems showed prolonged control over drug release (for ∼72 h) at acidic pH compared to DOX-encapsulated nanocarriers, as expected. We found that DOX-encapsulated nanoformulations triggered cardiotoxicity in primary cardiomyocytes more acutely, while conjugated systems such as PCPY-cDOX prevented cardiotoxicity by disabling the nuclear entry of the drug. Using 2D and 3D (spheroid) cultures of an ER + breast cancer cell line (MCF-7) and a triple-negative breast cancer cell line (MDA-MB-231), we unravel that, similar to encapsulated systems (PCPY-eDOX-type) as reported earlier, the PCPY-cDOX system suppresses cellular proliferation in both cell lines and enhances trafficking through 3D spheroids of MDA-MB-231 cells. Collectively, our studies indicate that PCPY-cDOX is less cardiotoxic as compared to noncovalently encapsulated variants without compromising the chemotherapeutic properties of the drug. Thus, our studies suggest that the appropriate selection of the nanocarrier for DOX delivery may prove fruitful in shifting the balance between low cardiotoxicity and triggering the chemotherapeutic potency of DOX.
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http://dx.doi.org/10.1021/acs.molpharmaceut.0c00963DOI Listing
December 2020

Molecular Perspectives of Mitochondrial Adaptations and Their Role in Cardiac Proteostasis.

Front Physiol 2020 27;11:1054. Epub 2020 Aug 27.

Department of Pathology and Translational Pathobiology, Louisiana State University Health Sciences Center, Shreveport, LA, United States.

Mitochondria are the key to properly functioning energy generation in the metabolically demanding cardiomyocytes and thus essential to healthy heart contractility on a beat-to-beat basis. Mitochondria being the central organelle for cellular metabolism and signaling in the heart, its dysfunction leads to cardiovascular disease. The healthy mitochondrial functioning critical to maintaining cardiomyocyte viability and contractility is accomplished by adaptive changes in the dynamics, biogenesis, and degradation of the mitochondria to ensure cellular proteostasis. Recent compelling evidence suggests that the classical protein quality control system in cardiomyocytes is also under constant mitochondrial control, either directly or indirectly. Impairment of cytosolic protein quality control may affect the position of the mitochondria in relation to other organelles, as well as mitochondrial morphology and function, and could also activate mitochondrial proteostasis. Despite a growing interest in the mitochondrial quality control system, very little information is available about the molecular function of mitochondria in cardiac proteostasis. In this review, we bring together current understanding of the adaptations and role of the mitochondria in cardiac proteostasis and describe the adaptive/maladaptive changes observed in the mitochondrial network required to maintain proteomic integrity. We also highlight the key mitochondrial signaling pathways activated in response to proteotoxic stress as a cellular mechanism to protect the heart from proteotoxicity. A deeper understanding of the molecular mechanisms of mitochondrial adaptations and their role in cardiac proteostasis will help to develop future therapeutics to protect the heart from cardiovascular diseases.
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http://dx.doi.org/10.3389/fphys.2020.01054DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7481364PMC
August 2020

Pleiotropic effects of mdivi-1 in altering mitochondrial dynamics, respiration, and autophagy in cardiomyocytes.

Redox Biol 2020 09 26;36:101660. Epub 2020 Jul 26.

Department of Molecular and Cellular Physiology, Louisiana State University Health Sciences Center, Shreveport, LA, 71103, USA; Department of Pathology and Translational Pathobiology, Louisiana State University Health Sciences Center, Shreveport, LA, 71103, USA. Electronic address:

Mitochondria are highly dynamic organelles that constantly undergo fission and fusion events to adapt to changes in the cellular environment. Aberrant mitochondrial fission has been associated with several types of cardiovascular dysfunction; inhibition of pathologically aberrant mitochondrial fission has been shown to be cardioprotective. Pathological fission is mediated by the excessive activation of GTPase dynamin-related protein 1 (Drp1), making it an attractive therapeutic target in numerous cardiovascular diseases. Mitochondrial division inhibitor (mdivi-1) is widely used small molecule reported to inhibit Drp1-dependent fission, elongate mitochondria, and mitigate injury. The purpose of our study was to understand the pleiotropic effects of mdivi-1 on mitochondrial dynamics, mitochondrial respiration, electron transport activities, and macro-autophagy. In this study, we found that mdivi-1 treatment decreased Drp1 expression, proteolytically cleaved L-OPA1, and altered the expression of OXPHOS complex proteins, resulting in increased superoxide production. The altered expression of OXPHOS complex proteins may be directly associated with decreased Drp1 expression, as Drp1 siRNA knockdown in cardiomyocytes showed similar effects. Results from an autophagy flux assay showed that mdivi-1 induced impaired autophagy flux that could be restored by Atg7 overexpression, suggesting that mdivi-1 mediated inhibition of macro-autophagy in cardiomyocytes. Treatment with mdivi-1 resulted in increased expression of p62, which is required for Atg7 overexpression-induced rescue of mdivi-1-mediated impaired autophagy flux. In addition, mdivi-1-dependent proteolytic processing of L-OPA1 was associated with increased mitochondrial superoxide production and altered expression of mitochondrial serine/proteases. Overall, the novel pleiotropic effect of mdivi-1 in cardiomyocytes included proteolytically cleaved L-OPA1, altered expression of OXPHOS complex proteins, and increased superoxide production, which together resulted in defects in mitochondrial respiration and inhibition of macro-autophagy.
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http://dx.doi.org/10.1016/j.redox.2020.101660DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7396909PMC
September 2020

Nanoparticles in tissue engineering: applications, challenges and prospects.

Int J Nanomedicine 2018 24;13:5637-5655. Epub 2018 Sep 24.

Biomedical Research Center, Qatar University, Doha, Qatar.

Tissue engineering (TE) is an interdisciplinary field integrating engineering, material science and medical biology that aims to develop biological substitutes to repair, replace, retain, or enhance tissue and organ-level functions. Current TE methods face obstacles including a lack of appropriate biomaterials, ineffective cell growth and a lack of techniques for capturing appropriate physiological architectures as well as unstable and insufficient production of growth factors to stimulate cell communication and proper response. In addition, the inability to control cellular functions and their various properties (biological, mechanical, electrochemical and others) and issues of biomolecular detection and biosensors, all add to the current limitations in this field. Nanoparticles are at the forefront of nanotechnology and their distinctive size-dependent properties have shown promise in overcoming many of the obstacles faced by TE today. Despite tremendous progress in the use of nanoparticles over the last 2 decades, the full potential of the applications of nanoparticles in solving TE problems has yet to be realized. This review presents an overview of the diverse applications of various types of nanoparticles in TE applications and challenges that need to be overcome for nanotechnology to reach its full potential.
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http://dx.doi.org/10.2147/IJN.S153758DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6161712PMC
November 2018

Advances in osteobiologic materials for bone substitutes.

J Tissue Eng Regen Med 2018 06 21;12(6):1448-1468. Epub 2018 May 21.

Biomedical Research Center, Qatar University, Doha, Qatar.

A significant challenge in the current orthopedics is the development of suitable osteobiologic materials that can replace the conventional allografts, autografts, and xenografts and thereby serve as implant materials as bone substitutes for bone repair or remodelling. The complex biology behind the nanostructure and microstructure of bones and their repair mechanisms, which involve various types of chemical and biomechanical signalling amongst different cells, has set strong requirements for biomaterials to be used in bone tissue engineering. This review presents an overview of various types of osteobiologic materials to facilitate the formation of the functional bone tissue and healing of the bone, covering metallic, ceramic, polymeric, and cell-based graft substitutes, as well as some biomolecular strategies including stem cells, extracellular matrices, growth factors, and gene therapies. Advantages and disadvantages of each type, particularly from the perspective of osteoinductive and osteoconductive capabilities, are discussed. Although the numerous challenges of bone regeneration in tissue engineering and regenerative medicine are yet to be entirely addressed, further advancements in osteobiologic materials will pave the way towards engineering fully functional bone replacement grafts.
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http://dx.doi.org/10.1002/term.2677DOI Listing
June 2018

Recent advances in application of biosensors in tissue engineering.

Biomed Res Int 2014 6;2014:307519. Epub 2014 Aug 6.

Department of Biochemistry and Molecular Genetics, Faculty of Medicine, American University of Beirut, Beirut 1107 2020, Lebanon.

Biosensors research is a fast growing field in which tens of thousands of papers have been published over the years, and the industry is now worth billions of dollars. The biosensor products have found their applications in numerous industries including food and beverages, agricultural, environmental, medical diagnostics, and pharmaceutical industries and many more. Even though numerous biosensors have been developed for detection of proteins, peptides, enzymes, and numerous other biomolecules for diverse applications, their applications in tissue engineering have remained limited. In recent years, there has been a growing interest in application of novel biosensors in cell culture and tissue engineering, for example, real-time detection of small molecules such as glucose, lactose, and H2O2 as well as serum proteins of large molecular size, such as albumin and alpha-fetoprotein, and inflammatory cytokines, such as IFN-g and TNF-α. In this review, we provide an overview of the recent advancements in biosensors for tissue engineering applications.
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http://dx.doi.org/10.1155/2014/307519DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4140114PMC
May 2015

Biomarkers for diagnosis of neonatal infections: A systematic analysis of their potential as a point-of-care diagnostics.

J Glob Health 2011 Dec;1(2):201-9

Child Health Research Foundation (CHRF), Department of Microbiology, Dhaka Shishu Hospital, Dhaka, Bangladesh.

Background: Neonatal infections annually claim lives of 1.4 million neonates worldwide. Until now, there is no ideal diagnostic test for detecting sepsis and thus management of possible sepsis cases often depends on clinical algorithm leading to empirical treatment. This often results in unnecessary antibiotic use, which may lead to emergence of antibiotic resistance. Biomarkers have shown great promise in diagnosis of sepsis and guiding appropriate treatment of neonates. In this study, we conducted a literature review of existing biomarkers to analyze their status for use as a point-of-care diagnostic in developing countries.

Methods: PubMed and EMBASE database were searched with keywords, 'infections', 'neonates', and 'biomarkers' to retrieve potentially relevant papers from the period 1980 to 2010. Leading hospitals and manufacturers were communicated to inquire about the cost, laboratory requirements and current standing of biomarkers in clinical use.

Results: The search returned 6407 papers on biomarkers; 65 were selected after applying inclusion and exclusion criteria. Among the studies, C-reactive protein (CRP), procalcitonin (PCT) and interleukin 6 (IL-6) were the most widely studied biomarkers and were considered to be most promising for diagnosing neonatal infections. About 90% of the studies were from developed countries; more than 50% were from Europe.

Conclusions: Extensive work is being performed to find the diagnostic and prognostic value of biomarkers. However, the methodologies and study design are highly variable. Despite numerous research papers on biomarkers, their use in clinical setting is limited to CRP. The methods for detection of biomarkers are far too advanced to be used at the community level where most of the babies are dying. It is important that a harmonized multi-site study is initiated to find a battery of biomarkers for diagnosis of neonatal infections.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3484777PMC
December 2011

Transcription factor YY1 interacts with retroviral integrases and facilitates integration of moloney murine leukemia virus cDNA into the host chromosomes.

J Virol 2010 Aug 2;84(16):8250-61. Epub 2010 Jun 2.

Department of Biotechnology, Graduate School of Engineering, Nagoya University, Furo-cho, Chikusa-ku, Nagoya 464-8603, Japan.

Retroviral integrases associate during the early viral life cycle with preintegration complexes that catalyze the integration of reverse-transcribed viral cDNA into the host chromosomes. Several cellular and viral proteins have been reported to be incorporated in the preintegration complex. This study demonstrates that transcription factor Yin Yang 1 binds to Moloney murine leukemia virus, human immunodeficiency virus type 1, and avian sarcoma virus integrases. The results of coimmunoprecipitation and in vitro pulldown assays revealed that Yin Yang 1 interacted with the catalytic core and C-terminal domains of Moloney murine leukemia virus and human immunodeficiency virus type 1 integrases, while the transcriptional repression and DNA-binding domains of the Yin Yang 1 molecule interacted with Moloney murine leukemia virus integrase. Immunoprecipitation of the cytoplasmic fraction of virus-infected cells followed by Southern blotting and chromatin immunoprecipitation demonstrated that Yin Yang 1 associated with Moloney murine leukemia virus cDNA in virus-infected cells. Yin Yang 1 enhanced the in vitro integrase activity of Moloney murine leukemia virus, human immunodeficiency virus type 1, and avian sarcoma virus integrases. Furthermore, knockdown of Yin Yang 1 in host cells by small interfering RNA reduced Moloney murine leukemia virus cDNA integration in vivo, although viral cDNA synthesis was increased, suggesting that Yin Yang 1 facilitates integration events in vivo. Taking these results together, Yin Yang 1 appears to be involved in integration events during the early viral life cycle, possibly as an enhancer of integration.
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http://dx.doi.org/10.1128/JVI.02681-09DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2916549PMC
August 2010

YY1 binds to regulatory element of chicken lysozyme and ovalbumin promoters.

Cytotechnology 2006 Nov 26;52(3):159-70. Epub 2006 Sep 26.

Department of Biotechnology, Graduate School of Engineering, Nagoya University, Furo-cho, Chikusa-ku, Nagoya, 464-8603, Japan.

Chicken lysozyme is highly expressed in the oviduct. The 5' regulatory region of this gene contains a negative element that represses transcription. To assess the molecular basis underlying the regulation of lysozyme gene expression, we investigated the binding protein to this region. Sequence motif analysis suggested the existence of putative YY1 binding sites in this regulatory region. Electrophoretic mobility shift assay showed the specific binding of YY1 to the negative element. In addition, chromatin immunoprecipitation assay indicated that YY1 specifically bound to the negative element in oviduct cells but not in erythrocytes. It was suggested by electrophoretic mobility shift assay and chromatin immunoprecipitation assay that YY1 also bound to the negative regulatory region in the promoter of the ovalbumin gene which also shows oviduct-specific expression. Western blot analysis showed that YY1 was expressed in relatively high levels in the oviduct and nucleus fractionation experiments showed that YY1 was localized both in chromosome and nuclear matrix fractions. These results suggest that there are some specific roles in the negative regulatory regions of these genes in relation to the multifunctional transcription factor YY1.
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http://dx.doi.org/10.1007/s10616-006-9017-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3449407PMC
November 2006

Chicken ovalbumin promoter is demethylated upon expression in the regions specifically involved in estrogen-responsiveness.

Biosci Biotechnol Biochem 2006 Jun;70(6):1438-46

Department of Biotechnology, Graduate School of Engineering, Nagoya University.

Here we report the methylation status of the chicken ovalbumin promoter. Genomic DNA of oviduct from immature chickens and laying hens was analyzed through bisulfite genomic sequencing. In the ovalbumin control locus up to the 6 kb upstream region, CpG sites were methylated in immature chickens, except for several sites, and almost all CpGs residing in DNase I hypersensitive sites I, II, and III, but not IV, were selectively unmethylated in ovalbumin expressing chickens. Chromatin immunoprecipitation assays showed that the ovalbumin control region was associated with acetylated histone H3 but not with dimethylated histone H3 at Lys 27. These results demonstrate that DNA demethylation was restricted to short DNA regions of DNase I hypersensitive sites, especially to those which participated in estrogen-responsiveness, even when cells expressed extremely high levels of ovalbumin and these sites were associated with acetylated histones.
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http://dx.doi.org/10.1271/bbb.50682DOI Listing
June 2006

Production of anti-CD2 chimeric antibody by recombinant animal cells.

J Biosci Bioeng 2004 ;98(4):298-303

Department of Biotechnology, Graduate School of Engineering, Nagoya University, Furo-cho, Chikusa-ku, Nagoya 464-8603, Japan.

Expression vectors for chimeric anti-CD2 antibody were constructed in order to clarify the importance of the expression ratio of heavy (H-) and light (L-) chains of antibody to antibody production in animal cells. The antibody genes were introduced into cells using plasmid DNA vectors or replication-defective retroviral vectors. Productivity was maximal when the expression ratio of H-and L-chains was 1:1, and decreased when the ratio was not equal. We also examined the expression of antibody using one-packed vectors in which the bicistronic expression of H- and L-chain genes was mediated by an internal ribosomal entry site (IRES) sequence derived from encephalomyocarditis virus (EMCV). The translation efficiency was unbalanced between 5'Cap- and IRES-dependent genes. Using the retroviral vectors, it was estimated that the IRES-dependent translation efficiency was 5-fold lower than the 5'Cap-dependent translation efficiency. The cells exhibiting an unbalanced expression of H- and L-chains tended to accumulate H-chain protein.
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http://dx.doi.org/10.1016/S1389-1723(04)00285-3DOI Listing
October 2005

Association between angiotensin I-converting enzyme gene polymorphism and hypertension in selected individuals of the Bangladeshi population.

J Biochem Mol Biol 2002 May;35(3):251-4

Department of Biochemistry and Molecular Biology, University of Dhaka, Dhaka-1000, Bangladesh.

The genetic factors that contribute to the development of coronary artery disease (CAD) are poorly understood. It is likely that multiple genes that act independently or synergistically contribute to the development of CAD and the outcome. Recently, an insertion/deletion (I/D) polymorphism of the human angiotensin I-converting enzyme (ACE) gene, a major component of the reninangiotensin system (RAS), was identified. The association of the ACE gene D allele with essential hypertension and CAD has been reported in the African-American, Chinese, and Japanese populations. However, other studies have failed to detect such an association. It has been suggested that these inconsistencies may be due to the difference in backgrounds of the population characteristics. In the present study, we investigated the I/D polymorphism of the ACE gene in 103 subjects of both sexes, consisting of 59 normal controls and 44 patients with hypertension. The allele and genotype frequency were significantly different between the hypertensive and control groups (p < 0.01). Among the three ACE I/D variants, the DD genotype was associated with the highest value of the mean systolic blood pressure [SBP] and mean diastolic blood pressure [DBP] (p = < 0.05) in men, but not in women. In the overall population, the mean SBP and DBP was highest in DD subjects, intermediate in I/D subjects, and the least in II subjects
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http://dx.doi.org/10.5483/bmbrep.2002.35.3.251DOI Listing
May 2002
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