title: Reduction of prohibitin expression contributes to left ventricular hypertrophy via enhancement of mitochondrial reactive oxygen species formation in spontaneous hypertensive rats.
abstract: Left ventricular hypertrophy (LVH) in hypertension is characterized by thickening of myocardium and decrease in heart chamber volume in response to mechanical or pathological stress, but the underlying molecular mechanisms remain to be defined. In this work, we investigate whether mitochondrial prohibitin (PHB) was involved in the progression of LVH in spontaneous hypertensive rats (SHR). First, it was found that mitochondrial dysfunction occurred in left ventricles of SHR. Through analysis using quantitative reverse transcription polymerase chain reaction and Western blotting, it was found that PHB mRNA and mitochondrial PHB levels in left ventricles of SHR were significantly lower than that in Wistar-Kyoto rats. Furthermore, PHB mRNA levels were negatively correlated to left ventricles weight-to-body weight ratio in SHR. Knockdown of PHB led to increased formation of mitochondrial reactive oxygen species (ROS) and reduced activities of complex I, mitochondrial adenosine triphosphate generation and mitochondrial membrane potential in cultured cardiomyocytes. Knockdown of PHB contributed to the cardiomyocyte hypertrophy, which could be attenuated by treatment with the Tempol. Angiotensin II (AngII) was increased in plasma and left ventricles of SHR. Incubation with AngII reduced mitochondrial PHB expression in cardiomyocytes, which was reversed when pretreated with losartan. In conclusion, reduction of PHB expression in left ventricles in SHR contributed to LVH, at least in part, through promoting mitochondrial ROS formation.
authors.affiliation: College of Chemistry and Biology, Donghua University , Shanghai , P. R. China.
authors.forename: H
authors.initials: H
authors.lastname: Zheng
authors.forename: G M
authors.initials: GM
authors.lastname: Lu
mesh_terms: D000255:Adenosine Triphosphate / Q000096:biosynthesis / Q000235:genetics; D000804:Angiotensin II / Q000097:blood / Q000235:genetics; D000818:Animals; D005786:Gene Expression Regulation; D055785:Gene Knockdown Techniques; D006352:Heart Ventricles / Q000378:metabolism*; D006973:Hypertension / Q000150:complications*; D017379:Hypertrophy, Left Ventricular / Q000209:etiology* / Q000235:genetics; D008297:Male; D053078:Membrane Potential, Mitochondrial / Q000235:genetics; D008929:Mitochondria, Heart / Q000235:genetics / Q000378:metabolism*; D000091402:Prohibitins; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D017382:Reactive Oxygen Species / Q000378:metabolism*; D012097:Repressor Proteins / Q000235:genetics* / Q000378:metabolism; D016276:Ventricular Function / Q000235:genetics
chemical_list: C000717332:Phb protein, rat; D000091402:Prohibitins; D017382:Reactive Oxygen Species; D012097:Repressor Proteins; D000804:Angiotensin II; D000255:Adenosine Triphosphate
keywords: angiotensin II; left ventricular hypertrophy; mitochondria; prohibitin; reactive oxygen species; spontaneously hypertensive rats