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Loss of NAMPT and SIRT2 but not SIRT1 attenuate GLO1 expression and activity in human skeletal muscle

Authors :
Edwin R. Miranda
Pallavi Varshney
Corey E. Mazo
James Shadiow
Andrew T. Ludlow
Jacob M. Haus
Source :
Redox Biology, Vol 75, Iss , Pp 103300- (2024)
Publication Year :
2024
Publisher :
Elsevier, 2024.

Abstract

Glyoxalase I (GLO1) is the primary enzyme for detoxification of the reactive dicarbonyl methylglyoxal (MG). Loss of GLO1 promotes accumulation of MG resulting in a recapitulation of diabetic phenotypes. We previously demonstrated attenuated GLO1 protein in skeletal muscle from individuals with type 2 diabetes (T2D). However, whether GLO1 attenuation occurs prior to T2D and the mechanisms regulating GLO1 abundance in skeletal muscle are unknown. GLO1 expression and activity were determined in skeletal muscle tissue biopsies from 15 lean healthy individuals (LH, BMI: 22.4 ± 0.7) and 5 individuals with obesity (OB, BMI: 32.4 ± 1.3). GLO1 protein was attenuated by 26 ± 0.3 % in OB compared to LH skeletal muscle (p = 0.019). Similar reductions for GLO1 activity were observed (p = 0.102). NRF2 and Keap1 expression were equivocal between groups despite a 2-fold elevation in GLO1 transcripts in OB skeletal muscle (p = 0.008). GLO1 knock-down (KD) in human immortalized myotubes promoted downregulation of muscle contraction and organization proteins indicating the importance of GLO1 expression for skeletal muscle function. SIRT1 KD had no effect on GLO1 protein or activity whereas, SIRT2 KD attenuated GLO1 protein by 28 ± 0.29 % (p

Details

Language :
English
ISSN :
22132317
Volume :
75
Issue :
103300-
Database :
Directory of Open Access Journals
Journal :
Redox Biology
Publication Type :
Academic Journal
Accession number :
edsdoj.318951f6a16d406dbf8a1199a23cdddf
Document Type :
article
Full Text :
https://doi.org/10.1016/j.redox.2024.103300