Ndufc2 Gene Inhibition Is Associated With Mitochondrial Dysfunction and Increased Stroke Susceptibility in an Animal Model of Complex Human Disease

Journal of the American Heart Association
S RubattuM Volpe

Abstract

The genetic basis of stroke susceptibility remains to be elucidated. STR1 quantitative trait locus (STR1/QTL) was identified on rat chromosome 1 of stroke-prone spontaneously hypertensive rat (SHRSP) upon Japanese-style stroke-permissive diet (JD), and it contributes to 20% of the stroke phenotype variance. Nine hundred eighty-six probe sets mapping on STR1 were selected from the Rat RAE230A array and screened through a microarray differential expression analysis in brains of SHRSP and stroke-resistant SHR (SHRSR) fed with either regular diet or JD. The gene encoding Ndufc2 (NADH dehydrogenase [ubiquinone] 1 subunit), mapping 8 Mb apart from STR1/QTL Lod score peak, was found significantly down-regulated under JD in SHRSP compared to SHRSR. Ndufc2 disruption altered complex I assembly and activity, reduced mitochondrial membrane potential and ATP levels, and increased reactive oxygen species production and inflammation both in vitro and in vivo. SHRSR carrying heterozygous Ndufc2 deletion showed renal abnormalities and stroke occurrence under JD, similarly to SHRSP. In humans, T allele variant at NDUFC2/rs11237379 was associated with significant reduction in gene expression and with increased occurrence of early-onset ischemic ...Continue Reading

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Citations

Sep 7, 2016·Oxidative Medicine and Cellular Longevity·Speranza RubattuMassimo Volpe
Nov 5, 2019·Autophagy·Maurizio ForteSebastiano Sciarretta
Nov 19, 2019·Oxidative Medicine and Cellular Longevity·Speranza RubattuSalvatore Raffa
Mar 14, 2019·Journal of Molecular Medicine : Official Organ of the Gesellschaft Deutscher Naturforscher Und Ärzte·Maurizio ForteSperanza Rubattu
Jul 14, 2017·Scientific Reports·Penn MuluhngwiCarolyn M Klinge
Jan 17, 2020·Genes·Rosita StanzioneSperanza Rubattu
Nov 23, 2017·Oxidative Medicine and Cellular Longevity·Giorgia PierelliSperanza Rubattu
Jun 10, 2019·Seminars in Cell & Developmental Biology·Maheshwor Thapa, Guido Dallmann

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Methods Mentioned

BETA
electrophoresis
PCR
Flow Cytometry
protein assay
ELISA
Assay
genotyping

Software Mentioned

Affymetrix
SPSS
custom Perl scripts
GCOS
Genome Analysis Toolkit ( GATK
Burrows Aligner ( BWA ‐

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