title: Does p49/STRAP, a SRF-binding protein (SRFBP1), modulate cardiac mitochondrial function in aging?
abstract: p49/STRAP (SRFBP1) is a transcriptional regulator that has been implicated in cardiac aging. p49/STRAP has a SRF binding domain and a BUD22 domain (which modulates cellular growth rate and cell size). We have observed that p49/STRAP alters the intracellular NAD/NADH ratio and induces protein deacetylation. Here we report that p49/STRAP overexpression caused the deacetylation of histone H4 on lysine 16 (H4K16) and suppressed the expression of PGC-1α as well as mitofusin-1 and mitofusin-2 at both the mRNA and protein levels. P49/STRAP also reduced mitochondrial size, mitochondrial membrane potential and the mitochondrial oxygen consumption rate. We noted that P49/STRAP expression was increased in the old versus young adult mouse hearts and also increased with advancing population doubling levels in cultured human umbilical vein endothelial cells (HUVECs). It is therefore very plausible that increased expression of p49/STRAP in late life may alter the status of histone acetylation and impact mitochondrial dynamics and thereby reduce mitochondrial function and cardiac performance during mammalian senescence.
authors.affiliation: Donald W. Reynolds Department of Geriatrics, University of Arkansas for Medical Sciences, Little Rock, AR 72205, United States.
authors.forename: Xiaomin
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Donald W. Reynolds Department of Geriatrics, University of Arkansas for Medical Sciences, Little Rock, AR 72205, United States.
authors.forename: Emmanuel D
authors.initials: ED
authors.lastname: Williams
authors.affiliation: Donald W. Reynolds Department of Geriatrics, University of Arkansas for Medical Sciences, Little Rock, AR 72205, United States.
authors.forename: Gohar
authors.initials: G
authors.lastname: Azhar
authors.affiliation: Donald W. Reynolds Department of Geriatrics, University of Arkansas for Medical Sciences, Little Rock, AR 72205, United States.
authors.forename: Steven C
authors.initials: SC
authors.lastname: Rogers
authors.affiliation: Donald W. Reynolds Department of Geriatrics, University of Arkansas for Medical Sciences, Little Rock, AR 72205, United States. Electronic address: weijeanne@uams.edu.
authors.forename: Jeanne Y
authors.initials: JY
authors.lastname: Wei
mesh_terms: D000375:Aging / Q000502:physiology*; D000818:Animals; D016922:Cellular Senescence; D005786:Gene Expression Regulation; D006657:Histones / Q000378:metabolism*; D061307:Human Umbilical Vein Endothelial Cells / Q000166:cytology; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D008929:Mitochondria, Heart / Q000235:genetics / Q000378:metabolism*; D009687:Nuclear Proteins / Q000378:metabolism; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D015534:Trans-Activators / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*
chemical_list: D006657:Histones; D009687:Nuclear Proteins; C486497:PPARGC1A protein, human; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D012333:RNA, Messenger; C496545:SRFBP1 protein, human; D015534:Trans-Activators; D014157:Transcription Factors; C496544:p49-STRAP protein, mouse
keywords: Histone acetylation; Mitochondrial oxygen consumption; Mitofusins; PGC-1α