Papers by Limbikani Kanyenda
Journal of Alzheimer's Disease, Feb 7, 2014
The CD147 protein is a ubiquitous multifunctional membrane receptor. Expression of CD147, which i... more The CD147 protein is a ubiquitous multifunctional membrane receptor. Expression of CD147, which is regulated by sterol carrier protein, reportedly modulates amyloid-β (Aβ), the neurotoxic peptide implicated in neuronal degeneration in Alzheimer's disease (AD). Given that high fat/cholesterol is linked to amyloid deposition in AD, we investigated if cholesterol and/or Aβ can alter CD147 expression in rat cortical neuronal cultures. Water-soluble cholesterol and Aβ42 dose-dependently increased CD147 protein expression, but reduced FL-AβPP protein expression. Cholesterol and Aβ42 treatment also increased lactate dehydrogenase release but to varying degrees. Upregulation of CD147 expression was probably mediated by oxidative stress, as H2O2 (3 μM) also induced CD147 protein expression in neuronal cultures. In light of these findings, we investigated if CD147 induction was cytoprotective, a compensatory response to injury, or alternatively, a cell death signal. To this end, we used recombinant adenovirus to overexpress human CD147 (in SH-SY5Y cells and primary cortical neurons), and pre-treated cultures with or without recombinant cyclophilin A (rCYPA) protein, prior to Aβ42 exposure. We showed that increased CD147 expression protected against Aβ42, only when rCYPA protein was added to neuronal cultures. Together, our findings reveal potentially important relationships between cholesterol loading, CD147 expression, Aβ toxicity, and the putative involvement of CYPA protein in neuroprotection in AD.
CD147, also known as basigin, extracellular matrix metalloproteinase inducer, neurothelin, tumour... more CD147, also known as basigin, extracellular matrix metalloproteinase inducer, neurothelin, tumour cell-derived collagenase stimulatory factor, M6, HT7, OX47 or gp42, is a transmembrane glycoprotein of the immunoglobulin super-family. It is expressed in many neuronal and non-neuronal tissues with high expression in the hippocampus, pre-frontal cortex, thyroid, heart, early erythroid, amygdala and placenta. This protein is involved in various cellular and biological functions such as lymphocyte migration and maturation, tissue repair, cancer progression, T and B lymphocyte activation and induction of extracellular matrix metalloproteinase. The CD147 protein interacts with with cyclophilin A, cyclophilin B, sterol carrier protein, caveolin-1 and integrins, and can influence beta amyloid peptide levels, a protein that is central to Alzheimer's disease pathology. Mechanisms through which CD147 regulates bata amyloid levels still remain unclear, thus the current study investigated the impact of high cholesterol and beta amyloid 42 loading on CD147 expression in rat primary cortical neuronal cultures. Its expression in human brain tissue from Alzheimer's disease and non-Alzheimer's disease dementias and APPswe transgenic mice fed on a high fat/high cholesterol diet were also determined. CD147 over expression experiments in rat primary cortical neuronal and SH-SY5Y cultures using recombinant adenoviruses (AdRSV-CD147 and AdRSV-Empty) in the presence and/or absence of cyclophilin A were employed to determine level of proection against oxidative stress and toxicity. Finally sequencing of the CD147 promoter region (-392 to-242 nucleotides) was perfomed to identify possible single neucrotide polymorphysims that may be linked to Alzheimer's disease pathology. iv The in vitro experiments conducted in this study have shown that cholesterol and beta amyloid loading and oxidative stress result in increased CD147 expression in rat primary cortical neuronal cultures and that CD147 protects neuronal cultures from beta amyloid toxicity only in the presence of cylophilin A. However in vivo experiments in animal model have shown that a high fat/high cholesterol diet does not affect brain CD147 levels as evidenced by unchanged expression levels in APPswe mice. Human studies have revealed a correlation between CD147 and γ-secretase complex components (nicastrin and presenilin 1) in the hippocampus. However, there is no difference in CD147 protein expression between hippocampus and frontal cortex from Alzheimer's disease patients. Sequencing of the CD147 promoter region, where sterol carrier protein binds to initiate CD147 transcription, has identified two novel single neucrotide polymorphysims (-61A>G and 37C>G). However, single neucrotide polymorphysims within this region are not associated with Alzheimer's disease pathology.
Journal of Virology & Antiviral Research
CD147, also known as basigin, extracellular matrix metalloproteinase inducer, neurothelin, tumour... more CD147, also known as basigin, extracellular matrix metalloproteinase inducer, neurothelin, tumour cell-derived collagenase stimulatory factor, M6, HT7, OX47 or gp42, is a transmembrane glycoprotein of the immunoglobulin super-family. It is expressed in many neuronal and non-neuronal tissues with high expression in the hippocampus, pre-frontal cortex, thyroid, heart, early erythroid, amygdala and placenta. This protein is involved in various cellular and biological functions such as lymphocyte migration and maturation, tissue repair, cancer progression, T and B lymphocyte activation and induction of extracellular matrix metalloproteinase. The CD147 protein interacts with with cyclophilin A, cyclophilin B, sterol carrier protein, caveolin-1 and integrins, and can influence beta amyloid peptide levels, a protein that is central to Alzheimer's disease pathology. Mechanisms through which CD147 regulates bata amyloid levels still remain unclear, thus the current study investigated the impact of high cholesterol and beta amyloid 42 loading on CD147 expression in rat primary cortical neuronal cultures. Its expression in human brain tissue from Alzheimer's disease and non-Alzheimer's disease dementias and APPswe transgenic mice fed on a high fat/high cholesterol diet were also determined. CD147 over expression experiments in rat primary cortical neuronal and SH-SY5Y cultures using recombinant adenoviruses (AdRSV-CD147 and AdRSV-Empty) in the presence and/or absence of cyclophilin A were employed to determine level of proection against oxidative stress and toxicity. Finally sequencing of the CD147 promoter region (-392 to-242 nucleotides) was perfomed to identify possible single neucrotide polymorphysims that may be linked to Alzheimer's disease pathology. iv The in vitro experiments conducted in this study have shown that cholesterol and beta amyloid loading and oxidative stress result in increased CD147 expression in rat primary cortical neuronal cultures and that CD147 protects neuronal cultures from beta amyloid toxicity only in the presence of cylophilin A. However in vivo experiments in animal model have shown that a high fat/high cholesterol diet does not affect brain CD147 levels as evidenced by unchanged expression levels in APPswe mice. Human studies have revealed a correlation between CD147 and γ-secretase complex components (nicastrin and presenilin 1) in the hippocampus. However, there is no difference in CD147 protein expression between hippocampus and frontal cortex from Alzheimer's disease patients. Sequencing of the CD147 promoter region, where sterol carrier protein binds to initiate CD147 transcription, has identified two novel single neucrotide polymorphysims (-61A>G and 37C>G). However, single neucrotide polymorphysims within this region are not associated with Alzheimer's disease pathology.
J Alzheimers Dis, 2014
The CD147 protein is a ubiquitous multifunctional membrane receptor. Expression of CD147, which i... more The CD147 protein is a ubiquitous multifunctional membrane receptor. Expression of CD147, which is regulated by sterol carrier protein, reportedly modulates amyloid-β (Aβ), the neurotoxic peptide implicated in neuronal degeneration in Alzheimer's disease (AD). Given that high fat/cholesterol is linked to amyloid deposition in AD, we investigated if cholesterol and/or Aβ can alter CD147 expression in rat cortical neuronal cultures. Water-soluble cholesterol and Aβ42 dose-dependently increased CD147 protein expression, but reduced FL-AβPP protein expression. Cholesterol and Aβ42 treatment also increased lactate dehydrogenase release but to varying degrees. Upregulation of CD147 expression was probably mediated by oxidative stress, as H2O2 (3 μM) also induced CD147 protein expression in neuronal cultures. In light of these findings, we investigated if CD147 induction was cytoprotective, a compensatory response to injury, or alternatively, a cell death signal. To this end, we used recombinant adenovirus to overexpress human CD147 (in SH-SY5Y cells and primary cortical neurons), and pre-treated cultures with or without recombinant cyclophilin A (rCYPA) protein, prior to Aβ42 exposure. We showed that increased CD147 expression protected against Aβ42, only when rCYPA protein was added to neuronal cultures. Together, our findings reveal potentially important relationships between cholesterol loading, CD147 expression, Aβ toxicity, and the putative involvement of CYPA protein in neuroprotection in AD.
Journal of Alzheimer's …, 2011
CD147, also known as basigin, EMMPRIN, neurothelin, TCSF, M6, HT7, OX47, or gp42, is a transmembr... more CD147, also known as basigin, EMMPRIN, neurothelin, TCSF, M6, HT7, OX47, or gp42, is a transmembrane glycoprotein of the immunoglobulin super-family. It is expressed in many neuronal and non-neuronal tissues including the hippocampus, pre-frontal cortex thyroid, heart, early erythroid, amygdala, and placenta. This protein is involved in various cellular and biological functions, such as lymphocyte migration and maturation, tissue repair cancer progression, T and B lymphocyte activation, and induction of extracellular matrix metalloproteinase. The CD147 protein interacts with other proteins such as cyclophilin A (CyPA), Cyclophilin B (CyPB), sterol carrier protein (SCP), caveolin-1 and integrins, and can influence amyloid-β (Aβ) peptide levels, a protein that is central to Alzheimer's disease (AD) pathogenesis. Mechanisms by which CD147 regulate Aβ levels remain unclear, thus in this review we discuss its involvement in Aβ production and clearance and potential mechanisms by which controlling CD147 levels could impact on Aβ accumulation and AD pathogenesis.
Critical Reviews in Clinical Laboratory Sciences, 2009
and-conditions-of-access.pdf This article may be used for research, teaching and private study pu... more and-conditions-of-access.pdf This article may be used for research, teaching and private study purposes. Any substantial or systematic reproduction, redistribution , reselling , loan or sub-licensing, systematic supply or distribution in any form to anyone is expressly forbidden. The publisher does not give any warranty express or implied or make any representation that the contents will be complete or accurate or up to date. The accuracy of any instructions, formulae and drug doses should be independently verified with primary sources. The publisher shall not be liable for any loss, actions, claims, proceedings, demand or costs or damages whatsoever or howsoever caused arising directly or indirectly in connection with or arising out of the use of this material.
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Papers by Limbikani Kanyenda