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This Article Figures Only Full Text Full Text (PDF) View Online Videos All Versions of this Article: j.jacc.2005.12.055v1 47/9/1882    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via ISI Web of Science (4) Citing Articles via Google Scholar Google Scholar Articles by Takeda, T. Articles by Kita, T. Search for Related Content PubMed PubMed Citation Articles by Takeda, T. Articles by Kita, T.

PRECLINICAL STUDY

Serofendic Acid, a Novel Substance Extracted From Fetal Calf Serum, Protects Against Oxidative Stress in Neonatal Rat Cardiac Myocytes

Toshihiro Takeda, MD^_*, Masaharu Akao, MD, PhD^_*,_*, Madoka Matsumoto-Ida, MD^_*, Masashi Kato, MD^_*, Hiroyuki Takenaka, MD^_*, Yasuki Kihara, MD, PhD^_*, Toshiaki Kume, PhD, Akinori Akaike, PhD and Toru Kita, MD, PhD^_*

^_* Department of Cardiovascular Medicine, Kyoto University Graduate School of Medicine, Kyoto, Japan
Department of Pharmaceutical Science, Kyoto University Graduate School of Pharmacology, Kyoto, Japan.

Manuscript received June 19, 2005; revised manuscript received December 14, 2005, accepted December 19, 2005.

^_* Reprint requests and correspondence: Dr. Masaharu Akao, Department of Cardiovascular Medicine, Kyoto University Graduate School of Medicine, 54 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto 606-8507, Japan. (Email: akao{at}kuhp.kyoto-u.ac.jp).

OBJECTIVES: We examined whether serofendic acid (SFA) has protective effects against oxidative stress in cardiac myocytes.

BACKGROUND: We previously identified a novel endogenous substance, SFA, from a lipophilic extract of fetal calf serum. Serofendic acid protects cultured neurons against the cytotoxicity of glutamate, nitric oxide, and oxidative stress.

METHODS: Primary cultures of neonatal rat cardiac myocytes were exposed to oxidative stress (H₂O₂, 100 µmol/l) to induce cell death. Effects of SFA were evaluated with a number of markers of cell death.

RESULTS: Pretreatment with SFA (100 µmol/l) significantly suppressed markers of cell death, as assessed by terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling staining and cell viability assay. Loss of mitochondrial membrane potential (_m) is a critical step of the death pathway, which is triggered by matrix calcium overload and reactive oxygen species. Serofendic acid prevented the _m loss induced by H₂O₂ in a concentration-dependent manner (with saturation by 100 µmol/l). Serofendic acid remarkably suppressed the H₂O₂-induced matrix calcium overload and intracellular accumulation of reactive oxygen species. The protective effect of SFA was comparable to that of a mitochondrial adenosine triphosphate-sensitive potassium (mitoK_ATP) channel opener, diazoxide. Furthermore, mitoK_ATP channel blocker, 5-hydroxydecanoate (500 µmol/l), abolished the protective effect of SFA. Co-application of SFA (100 µmol/l) and diazoxide (100 µmol/l) did not show an additive effect. Thus, SFA inhibited the oxidant-induced mitochondrial death pathway, presumably through activation of the mitoK_ATP channel.

CONCLUSIONS: Serofendic acid protects cardiac myocytes against oxidant-induced cell death by preserving the functional integrity of mitochondria.

Abbreviations and Acronyms   5-HD = 5-hydroxydecanoate   m = mitochondrial membrane potential   [Ca2+]m = mitochondrial matrix calcium   DAPI = 4’,6-diamidino-2-phenylindole   DCF = chloromethyl-2,7-dichlorodihydrofluorescein diacetate   DMEM = Dulbecco’s Modified Eagle Medium   FACS = fluorescence-activated cell sorter   MitoKATP = mitochondrial adenosine triphosphate-sensitive potassium   MPTP = mitochondrial permeability transition pore   ROS = reactive oxygen species   SFA = serofendic acid   TMRE = tetramethylrhodamine ethyl ester   TUNEL = terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling

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