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SUBVERSION OF SCHWANN CELL GLUCOSE METABOLISM BY MYCOBACTERIUM LEPRAE
Metabolismo celular
Mitocôndria
Micobactérias
Estresse oxidativo
Hanseníase
Glutationa
Neurônio
Terapia de hospedeiro-alvo
Glucose-6-phosphate dehydrogenase (G6PD or G6PDH)
Mitochondria
Mycobacteria
Neuron
Oxidative stress
Pentose phosphate pathway (PPP)
Leprosy
Glutathione
Host-target therapy
Produção científica do Laboratório de Hanseníase.
Produção científica do Laboratório de Microbiologia Celular.
There was an error in Fig. 2 L. Fig. 2L incorrectly indicated that the diameter of the mitochondria was measured in nanometers instead of the area in micrometers. This error has now been corrected. This error does not affect the results or conclusions of the work.
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Resumo em Inglês
Mycobacterium leprae, the intracellular etiological agent of leprosy, infects Schwann promoting irreversible physical disabilities and deformities. These cells are responsible for myelination and maintenance of axonal energy metabolism through export of metabolites, such as lactate and pyruvate. In the present work, we observed that infected Schwann cells increase glucose uptake with a concomitant increase in glucose-6-phosphate dehydrogenase (G6PDH) activity, the key enzyme of the oxidative pentose pathway. We also observed a mitochondria shutdown in infected cells and mitochondrial swelling in pure neural leprosy nerves. The classic Warburg effect described in macrophages infected by Mycobacterium avium was not observed in our model, which presented a drastic reduction in lactate generation and release by infected Schwann cells. This effect was followed by a decrease in lactate dehydrogenase isoform M (LDH-M) activity and an increase in cellular protection against hydrogen peroxide insult in a pentose phosphate pathway and GSH-dependent manner. M. leprae infection success was also dependent of the glutathione antioxidant system and its main reducing power source, the pentose pathway, as demonstrated by a 50 and 70% drop in intracellular viability after treatment with the GSH synthesis inhibitor buthionine sulfoximine, and aminonicotinamide (6-ANAM), an inhibitor of G6PDH 6-ANAM, respectively. We concluded that M. leprae could modulate host cell glucose metabolism to increase the cellular reducing power generation, facilitating glutathione regeneration and consequently free-radical control. The impact of this regulation in leprosy neuropathy is discussed.
Palavras-chave
Mycobacterium lepraeMetabolismo celular
Mitocôndria
Micobactérias
Estresse oxidativo
Hanseníase
Glutationa
Neurônio
Terapia de hospedeiro-alvo
Palavras-chave em inglês
Cell metabolismGlucose-6-phosphate dehydrogenase (G6PD or G6PDH)
Mitochondria
Mycobacteria
Neuron
Oxidative stress
Pentose phosphate pathway (PPP)
Leprosy
Glutathione
Host-target therapy
Editor
Elsevier
Referência
MEDEIROS, Rychelle Clayde Affonso et al. Subversion of schwann cell glucose metabolism by mycobacterium leprae. Journal of Biological Chemistry, v. 291, n. 41, p. 21375-21387, Oct. 2016.DOI
10.1074/jbc.M116.725283ISSN
0021-9258Notas
Produção científica do Laboratório de Biologia Estrutural.Produção científica do Laboratório de Hanseníase.
Produção científica do Laboratório de Microbiologia Celular.
There was an error in Fig. 2 L. Fig. 2L incorrectly indicated that the diameter of the mitochondria was measured in nanometers instead of the area in micrometers. This error has now been corrected. This error does not affect the results or conclusions of the work.
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