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Difference between revisions of "Machado 2019 MitoFit Preprint Arch EA"

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{{MitoFit page name}}
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{{Publication
{{Publication
|title=Crispim Marcell , Verdaguer IB, Katzin AM (2019) Effects of atovaquone and 4-nitrobenzoate on ''Plasmodium falciparum'' respiration. MitoFit Preprint Arch  doi:10.26124/mitofit:ea19.MiPSchool.0007.
|title=Machado Ivo F, Teodoro JS, Palmeira CM, Rolo AP (2019) Interplay between metformin and miR-378a-3p in cells under hyperglycaemia. https://doi.org/10.26124/mitofit:ea19.MiPSchool.0008
|info=[[File:MitoFit Preprint Arch pdf.png|left|160px|link=https://wiki.oroboros.at/images/8/81/Crispim_2019_MitoFit_Preprint_Arch_doi_10.26124mitofitea19.MiPSchool.0007.pdf |MitoFit pdf]]  <big><big>'''[https://wiki.oroboros.at/images/8/81/Crispim_2019_MitoFit_Preprint_Arch_doi_10.26124mitofitea19.MiPSchool.0007.pdf Effects of atovaquone and 4-nitrobenzoate on ''Plasmodium falciparum'' respiration]'''</big></big>
|info=MitoFit Preprint Arch EA19.8 [[File:MitoFit Preprint Arch pdf.png|left|160px|link=http://www.mitofit.org/images/9/9d/Machado_2019_MitoFit_Preprint_Arch_doi_10.26214mitofitea.MiPSchool.0008.pdf |MitoFit pdf]]  [http://www.mitofit.org/images/9/9d/Machado_2019_MitoFit_Preprint_Arch_doi_10.26214mitofitea.MiPSchool.0008.pdf Interplay between metformin and miR-378a-3p in cells under hyperglycaemia]
|authors=Crispim M, Verdaguer IB, Katzin AM
|authors=Machado IF, Teodoro JS, Palmeira CM, Rolo AP
|year=2019
|year=2019
|journal=MitoFit Preprint Arch
|journal=MitoFit Preprint Arch
|abstract=Version 1 ('''v1''') '''2019-06-17''' [https://wiki.oroboros.at/images/8/81/Crispim_2019_MitoFit_Preprint_Arch_doi_10.26124mitofitea19.MiPSchool.0007.pdf doi:10.26124/mitofit:ea19.MiPSchool.0007]
|abstract=Version 1 ('''v1''') '''2019-06-17''' [http://www.mitofit.org/images/9/9d/Machado_2019_MitoFit_Preprint_Arch_doi_10.26214mitofitea.MiPSchool.0008.pdf doi:10.26124/mitofit:ea19.MiPSchool.0008]


Although atovaquone is one of the newest antimalarial compounds discovered, resistant parasites have already been reported1. Atovaquone mechanism of action is established to be the competition with ubiquinol (UQH2) for the bc1 union at mitochondrial cytochrome bc1 complex and preventing the parasite from maintaining an oxidized ubiquinone (UQ) pool, essential for the DHODH activity and consequently for the pyrimidine's biosynthesis. In this sense, possible inhibitors of the ubiquinone biosynthesis pathway would be candidates by stimulating the effects of atovaquone. 4-nitrobenzoate (4-NB) is a well-known inhibitor of 4HPT (4-hydroxybenzoate polyprenyltransferase), the first enzyme of UQ biosynthesis. 4-NB also showed an important effect on reducing the UQs pool in P. falciparum. Herein is presenting the effect of atovaquone and 4-NB on parasitic respiration UQ biosynthesis. The purpose of this study was to better understand the atovaquone mechanism of action in a molecular scale, drug target potential of UQ biosynthesis. Oxygen consumption assays revealed 4-NB potentiates atovaquone mitochondrial effects and showed itself the ability to decrease the respiration rate. - ''Extended abstract''
Metformin is commonly used for the treatment of Type 2 Diabetes Mellitus (T2DM) being known for its role in the impairment of hepatic gluconeogenesis. However, it has been associated with the upregulation of microRNAs (miRNAs) involved in T2DM and cancer. Recently, it was reported that metformin promoted the expression of miR-378a-3p in HepG2 cells [1]. This miRNA is embedded in the Ppargc1b gene and has been reported to be an important player in the amelioration of obesity through the activation of the pyruvate-phosphoenolpyruvate (PEP) futile cycle in skeletal muscle [2]. Additionally, this miRNA has also been implicated in the regulation of autophagy in skeletal muscle [3] suggesting that it may also be involved in the removal of damaged mitochondria through mitochondria. In order to study this relation, Sesn2 KD cells were generated given that SESN2 is a stress-inducible protein and it was reported to be crucial in the induction of mitophagy [4]. Additionally, in the current study we explore the importance of miR-378a-3p in the improvement of mitochondrial function in C2C12 cells exposed to hyperglycaemia and demonstrate a possible interplay between metformin and the miRNA in these conditions. - ''Extended abstract''
|keywords=
|keywords=[[Diabetes]]
|editor=[[Iglesias-Gonzalez J]]
|editor=[[Iglesias-Gonzalez J]]
|mipnetlab=
|mipnetlab=PT Coimbra Laranjinha J
}}
}}


== Affiliations ==
== Affiliations ==
Crispim Marcell(1) , Verdaguer IB(1), Katzin AM(1)
Machado IF(1), Teodoro JS(1), Palmeira CM(1), Rolo AP(1)
::::# Dept. of Parasitology, Laboratório de Malária, Univ. of Sao Paulo, Sao Paulo, Brazil. Av. Prof. Lineu Prestes, 1374 - Edifício Biomédicas II - Cidade Universitária "Armando Salles Oliveira" - CEP: 05508-000.- marcell@usp.br
::::# Dept of Life Sciences and Center for Neurosciences and Cell Biology, Univ of Coimbra. - ivofmachado@gmail.com




== Results ==
== Results ==
[[File:Crispim 2019 MitoFit Preprin Arch EA Figure 1.png|700px]]
[[File:Machado 2019 MitoFit Preprint Arch EA Figure 1.png]]
[[File:Machado 2019 MitoFit Preprint Arch EA Figure 2.png]]


== References ==
== References ==
:::# Staines HM, Burrow R, Teo BH, Chis Ster I, Kremsner PG, Krishna S (2018) Clinical implications of Plasmodium resistance to atovaquone/proguanil: a systematic review and meta-analysis. J Antimicrob Chemother 73(3):581-595.
:::# Zhou J, Han S, Qian W, Gu Y, Li X, Yang K (2018) Metformin induces miR-378 to downregulate the CDK1, leading to suppression of cell proliferation in hepatocellular carcinoma. OncoTargets Ther 11:4451-4459.
:::# Trager W, Jensen JB (1976) Human malaria parasites in continuous culture. J Parasitol 91(3):484-6.
:::# Zhang Y, Li C, Li H, Song Y, Zhao Y, Zhai L, Wang H, Zhong R, Tang H, Zhu D (2016) MiR-378 activates the pyruvate-PEP futile cycle and enhances lipolysis to ameliorate obesity in mice. EBioMedicine 5:93-104.
:::# Tonhosolo R, Gabriel HB, Matsumura HY, Cabral FJ, Yamamoto MM, D’Alexandri FL, Sussmann RAC, Belmonte R, Peres VJ, Crick DC, Wunderlich G, Kimura EA, Katzin AM (2010) Intraerythrocytic stages of Plasmodium falciparum biosynthesize menaquinone. FEBS Lett 584: 4761–4768.
:::# Li Y, Jiang J, Liu W, Wang H, Zhao L, Liu S, Li P, Zhang S, Sun C, Wu Y, Yu S, Li X, Zhang H, Qian H, Zhang D, Guo F, Zhai Q, Ding Q, Wang L, Ying H (2018) microRNA-378 promotes autophagy and inhibits apoptosis in skeletal muscle. Proc Natl Acad Sci U S A 115:E10849-E10858.
:::# Lambros C, Vanderberg JP (1979) Synchronization of Plasmodium falciparum erythrocytic stages in culture. J. Parasitol 65: 418–20.
:::# Kumar A, Shaha C (2018) SESN2 facilitates mitophagy by helping Parkin translocation through ULK1 mediated Beclin1 phosphorylation. Sci Rep 8:615.
:::# Murphy AD, Doeller JE, Hearn B, Lang-Unnasch N (1997) Plasmodium falciparum: cyanide-resistant oxygen consumption, Exp Parasitol 87: 112–120.
:::# Carrer M, Liu N, Grueter CE, Williams AH, Frisard MI, Hulver MW, Bassel-Duby R, Olson EN (2012) Control of mitochondrial metabolism and systemic energy homeostasis by microRNAs 378 and 378*. Proc Natl Acad Sci U S A 109:15330-15335.
:::# Forsman U, Sjöberg M, Turunen M, Sindelar PJ (2010) 4-Nitrobenzoate inhibits coenzyme Q biosynthesis in mammalian cell cultures. Nat Chem Biol 6(7):515-7.  


== Event ==
::::» [[MiPschool Coimbra 2019]]
== Preprints for [[Gentle Science]] ==
{{MitoFit preprint}}


{{Labeling
{{Labeling
|area=
|area=Pharmacology;toxicology
|organism=
|preparations=
|enzymes=
|topics=
|couplingstates=
|instruments=Oxygraph-2k
|instruments=Oxygraph-2k
|additional=Metformin, Preprints
}}
}}

Latest revision as of 08:28, 8 January 2023


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Machado 2019 MitoFit Preprint Arch EA

Publications in the MiPMap
Machado Ivo F, Teodoro JS, Palmeira CM, Rolo AP (2019) Interplay between metformin and miR-378a-3p in cells under hyperglycaemia. https://doi.org/10.26124/mitofit:ea19.MiPSchool.0008

» MitoFit Preprint Arch EA19.8

MitoFit pdf

Interplay between metformin and miR-378a-3p in cells under hyperglycaemia

Machado IF, Teodoro JS, Palmeira CM, Rolo AP (2019) MitoFit Preprint Arch

Abstract: Version 1 (v1) 2019-06-17 doi:10.26124/mitofit:ea19.MiPSchool.0008

Metformin is commonly used for the treatment of Type 2 Diabetes Mellitus (T2DM) being known for its role in the impairment of hepatic gluconeogenesis. However, it has been associated with the upregulation of microRNAs (miRNAs) involved in T2DM and cancer. Recently, it was reported that metformin promoted the expression of miR-378a-3p in HepG2 cells [1]. This miRNA is embedded in the Ppargc1b gene and has been reported to be an important player in the amelioration of obesity through the activation of the pyruvate-phosphoenolpyruvate (PEP) futile cycle in skeletal muscle [2]. Additionally, this miRNA has also been implicated in the regulation of autophagy in skeletal muscle [3] suggesting that it may also be involved in the removal of damaged mitochondria through mitochondria. In order to study this relation, Sesn2 KD cells were generated given that SESN2 is a stress-inducible protein and it was reported to be crucial in the induction of mitophagy [4]. Additionally, in the current study we explore the importance of miR-378a-3p in the improvement of mitochondrial function in C2C12 cells exposed to hyperglycaemia and demonstrate a possible interplay between metformin and the miRNA in these conditions. - Extended abstract Keywords: Diabetes Bioblast editor: Iglesias-Gonzalez J O2k-Network Lab: PT Coimbra Laranjinha J


Affiliations

Machado IF(1), Teodoro JS(1), Palmeira CM(1), Rolo AP(1)

  1. Dept of Life Sciences and Center for Neurosciences and Cell Biology, Univ of Coimbra. - ivofmachado@gmail.com


Results

Machado 2019 MitoFit Preprint Arch EA Figure 1.png Machado 2019 MitoFit Preprint Arch EA Figure 2.png

References

  1. Zhou J, Han S, Qian W, Gu Y, Li X, Yang K (2018) Metformin induces miR-378 to downregulate the CDK1, leading to suppression of cell proliferation in hepatocellular carcinoma. OncoTargets Ther 11:4451-4459.
  2. Zhang Y, Li C, Li H, Song Y, Zhao Y, Zhai L, Wang H, Zhong R, Tang H, Zhu D (2016) MiR-378 activates the pyruvate-PEP futile cycle and enhances lipolysis to ameliorate obesity in mice. EBioMedicine 5:93-104.
  3. Li Y, Jiang J, Liu W, Wang H, Zhao L, Liu S, Li P, Zhang S, Sun C, Wu Y, Yu S, Li X, Zhang H, Qian H, Zhang D, Guo F, Zhai Q, Ding Q, Wang L, Ying H (2018) microRNA-378 promotes autophagy and inhibits apoptosis in skeletal muscle. Proc Natl Acad Sci U S A 115:E10849-E10858.
  4. Kumar A, Shaha C (2018) SESN2 facilitates mitophagy by helping Parkin translocation through ULK1 mediated Beclin1 phosphorylation. Sci Rep 8:615.
  5. Carrer M, Liu N, Grueter CE, Williams AH, Frisard MI, Hulver MW, Bassel-Duby R, Olson EN (2012) Control of mitochondrial metabolism and systemic energy homeostasis by microRNAs 378 and 378*. Proc Natl Acad Sci U S A 109:15330-15335.


Event

» MiPschool Coimbra 2019


Preprints for Gentle Science

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Labels: MiParea: Pharmacology;toxicology 





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