Gender-specific proteomic alterations in glycolytic and mitochondrial pathways in aging monkey hearts

TY - JOUR

T1 - Gender-specific proteomic alterations in glycolytic and mitochondrial pathways in aging monkey hearts

AU - Yan, L.

AU - Ge, H.

AU - Li, H.

AU - Lieber, S. C.

AU - Natividad, F.

AU - Resuello, R. R.G.

AU - Kim, S. J.

AU - Akeju, S.

AU - Sun, A.

AU - Loo, K.

AU - Peppas, A. P.

AU - Rossi, F.

AU - Lewandowski, E. D.

AU - Thomas, A. P.

AU - Vatner, S. F.

AU - Vatner, D. E.

N1 - Funding Information: Supported by NIH Grants AG-14121, HL-59139, HL-33107, HL-69020, HL-62442, HL-65182, HL-65183, BIRCWH Award HD01457, AHA Grant 0030125N, NSF 0100831, and NJ Commission on Higher Education Leasing Fund.

PY - 2004/11

Y1 - 2004/11

N2 - We utilized proteomic techniques in a primate model (Macaca fascicularis) of aging to determine potential mechanisms to explain gender differences in protection of the aging heart. The majority of prior work in this field utilized rodent models, and importantly no prior study utilized a proteomic approach in the aging heart. We studied changes in proteins in seven monkeys in each group (young and old males and females (YMs, OMs, YFs, and OFs, respectively)), and used two-dimensional gel electrophoresis in combination with mass spectrometry in five monkeys in each group. We found decreases (P < 0.05) in the expression of key enzymes in glycolysis (e.g. pyruvate kinase, α-enolase, triosephosphate isomerase), glucose oxidation (e.g. pyruvate dehydrogenase E1 β-subunit), and the tricarboxylic acid (TCA) cycle (2-oxoglutarate dehydrogenase) in left ventricular (LV) samples from OM monkeys; these changes in glycolytic, glucose oxidation, and TCA enzymes were not observed either in YMs, YFs or OFs. We found additional gender differences in the reduced expression and function of proteins that are responsible for electron transport and oxidative phosphorylation in mitochondria only in hearts from OM monkeys, with corresponding decreased oxidation rates with NADH and ascorbate-N,N, N′,N′ ́ ́-tetramethyl-p-phenylenediamine substrates. The changes in glycolytic and mitochondrial metabolic pathways in OM monkey hearts are similar to changes observed in hearts affected by diabetes or LV dysfunction, and could be involved in the mechanism for the cardiomyopathy of aging. The sparing of these changes in OF hearts could be involved in the mechanism mediating delayed cardiovascular risk in OFs.

AB - We utilized proteomic techniques in a primate model (Macaca fascicularis) of aging to determine potential mechanisms to explain gender differences in protection of the aging heart. The majority of prior work in this field utilized rodent models, and importantly no prior study utilized a proteomic approach in the aging heart. We studied changes in proteins in seven monkeys in each group (young and old males and females (YMs, OMs, YFs, and OFs, respectively)), and used two-dimensional gel electrophoresis in combination with mass spectrometry in five monkeys in each group. We found decreases (P < 0.05) in the expression of key enzymes in glycolysis (e.g. pyruvate kinase, α-enolase, triosephosphate isomerase), glucose oxidation (e.g. pyruvate dehydrogenase E1 β-subunit), and the tricarboxylic acid (TCA) cycle (2-oxoglutarate dehydrogenase) in left ventricular (LV) samples from OM monkeys; these changes in glycolytic, glucose oxidation, and TCA enzymes were not observed either in YMs, YFs or OFs. We found additional gender differences in the reduced expression and function of proteins that are responsible for electron transport and oxidative phosphorylation in mitochondria only in hearts from OM monkeys, with corresponding decreased oxidation rates with NADH and ascorbate-N,N, N′,N′ ́ ́-tetramethyl-p-phenylenediamine substrates. The changes in glycolytic and mitochondrial metabolic pathways in OM monkey hearts are similar to changes observed in hearts affected by diabetes or LV dysfunction, and could be involved in the mechanism for the cardiomyopathy of aging. The sparing of these changes in OF hearts could be involved in the mechanism mediating delayed cardiovascular risk in OFs.

KW - 2D GE

KW - Aging

KW - BW

KW - Gender

KW - Glycolysis

KW - IEF

KW - LV

KW - Mitochondria

KW - OF

KW - OM

KW - PAGE

KW - Proteomics

KW - TCA

KW - YF

KW - YM

KW - body weight

KW - iso-electric focusing

KW - left ventricular

KW - old female

KW - old male

KW - tricarboxylic acid

KW - two-dimensional gel electrophoresis

KW - young female

KW - young male

UR - http://www.scopus.com/inward/record.url?scp=7444251178&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=7444251178&partnerID=8YFLogxK

U2 - 10.1016/j.yjmcc.2004.06.012

DO - 10.1016/j.yjmcc.2004.06.012

M3 - Article

C2 - 15522269

SN - 0022-2828

VL - 37

SP - 921

EP - 929

JO - Journal of Molecular and Cellular Cardiology

JF - Journal of Molecular and Cellular Cardiology

IS - 5

ER -