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1.
J Biol Chem ; 299(12): 105360, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37863263

RESUMO

Protein arginine N-methyltransferases are a family of epigenetic enzymes responsible for monomethylation or dimethylation of arginine residues on histones. Dysregulation of protein arginine N-methyltransferase activity can lead to aberrant gene expression and cancer. Recent studies have shown that PRMT2 expression and histone H3 methylation at arginine 8 are correlated with disease severity in glioblastoma multiforme, hepatocellular carcinoma, and renal cell carcinoma. In this study, we explore a noncatalytic mechanistic role for PRMT2 in histone methylation by investigating interactions between PRMT2, histone peptides and proteins, and other PRMTs using analytical and enzymatic approaches. We quantify interactions between PRMT2, peptide ligands, and PRMT1 in a cofactor- and domain-dependent manner using differential scanning fluorimetry. We found that PRMT2 modulates the substrate specificity of PRMT1. Using calf thymus histones as substrates, we saw that a 10-fold excess of PRMT2 promotes PRMT1 methylation of both histone H4 and histone H2A. We found equimolar or a 10-fold excess of PRMT2 to PRMT1 can improve the catalytic efficiency of PRMT1 towards individual histone substrates H2A, H3, and H4. We further evaluated the effects of PRMT2 towards PRMT1 on unmodified histone octamers and mononucleosomes and found marginal PRMT1 activity improvements in histone octamers but significantly greater methylation of mononucleosomes in the presence of 10-fold excess of PRMT2. This work reveals the ability of PRMT2 to serve a noncatalytic role through its SH3 domain in driving site-specific histone methylation marks.


Assuntos
Histonas , Proteína-Arginina N-Metiltransferases , Arginina/metabolismo , Histonas/metabolismo , Metilação , Proteína-Arginina N-Metiltransferases/metabolismo , Fluorometria , Especificidade por Substrato , Estabilidade Proteica , Ligação Proteica , Domínios Proteicos , Ligantes , Humanos
2.
Afr J Reprod Health ; 26(5): 57-62, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-37585097

RESUMO

This research was designed to find out the attitude and knowledge of women between 45 and 65 years on menopause syndrome and its management. The study was conducted in University College Hospital located in Ibadan North Local Government of Oyo state. A self-designed forced-choice questionnaire was distributed to 100 women using random sampling technique. Furthermore, our study showed that most women view the onset of menopause positively and that few seek treatment. They report relatively low prevalence of menopausal symptoms, with the most significant being irregular menstrual cycles and increased blood pressure and urinary tract infections. Furthermore, our study revealed that 41% of the participants had no idea why their menstrual period stopped, while why 60% of the women had no idea what could be done to reduce menopausal symptoms. This study reveals a low level of awareness about menopausal syndrome and more should be done.


Assuntos
Atitude Frente a Saúde , Menopausa , Feminino , Humanos , Nigéria/epidemiologia , Universidades , Menopausa/fisiologia , Inquéritos e Questionários , Hospitais
3.
African Journal of Reproductive Health ; 26(5): 1-6, May 2022;. Tables
Artigo em Inglês | AIM (África) | ID: biblio-1382093

RESUMO

This research was designed to find out the attitude and knowledge of women between 45 and 65 years on menopause syndrome and its management. The study was conducted in University College Hospital located in Ibadan North Local Government of Oyo state. A self-designed forced-choice questionnaire was distributed to 100 women using random sampling technique. Furthermore, our study showed that most women view the onset of menopause positively and that few seek treatment. They report relatively low prevalence of menopausal symptoms, with the most significant being irregular menstrual cycles and increased blood pressure and urinary tract infections. Furthermore, our study revealed that 41% of the participants had no idea why their menstrual period stopped, while why 60% of the women had no idea what could be done to reduce menopausal symptoms. This study reveals a low level of awareness about menopausal syndrome and more should be done. (Afr J Reprod Health 2022; 26[5]: 57-62).


Assuntos
Menopausa , Acessibilidade aos Serviços de Saúde , Ciclo Menstrual , Síndrome , Mulheres
4.
Genome ; 64(4): 400-415, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33197212

RESUMO

In the absence of a vaccine, the treatment of SARS-CoV2 has focused on eliminating the virus with antivirals or mitigating the cytokine storm syndrome (CSS) that leads to the most common cause of death: respiratory failure. Herein we discuss the mechanisms of antiviral treatments for SARS-CoV2 and treatment strategies for the CSS. Antivirals that have shown in vitro activity against SARS-CoV2, or the closely related SARS-CoV1 and MERS-CoV, are compared on the enzymatic level and by potency in cells. For treatment of the CSS, we discuss medications that reduce the effects or expression of cytokines involved in the CSS with an emphasis on those that reduce IL-6 because of its central role in the development of the CSS. We show that some of the medications covered influence the activity or expression of enzymes involved in epigenetic processes and specifically those that add or remove modifications to histones or DNA. Where available, the latest clinical data showing the efficacy of the medications is presented. With respect to their mechanisms, we explain why some medications are successful, why others have failed, and why some untested medications may yet prove useful.


Assuntos
Antivirais/uso terapêutico , Tratamento Farmacológico da COVID-19 , Síndrome da Liberação de Citocina/tratamento farmacológico , Síndrome da Liberação de Citocina/virologia , Citocinas , Epigênese Genética , Expressão Gênica , Humanos , Interleucina-6 , SARS-CoV-2/efeitos dos fármacos
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