title: [Relationship between apoptosis and alteration of the energetic metabolism pathways of hypertrophic cardiomyocytes induced by hypoxia-reoxygenation].
abstract: The apoptosis of cardiomyocytes plays a pivotal role in the pathogenesis of cardiac failure transformed from cardiac hypertrophy, so that suppression of cardiomyocytes apoptosis is an effective pharmacotherapeutic target to prevent cardiac failure. This study focused on the relationship between apoptosis and alteration of the energetic metabolism pathways of hypertrophic cardiomyocytes induced by hypoxia-reoxygenation. Cardiomyocyte hypertrophy was induced by angiotensin II (0.1 mumol/L ) and norepinephrine (1 mumol/L), and the cells were cultured under the condition of hypoxia ( 95% N2 and 5% CO2, the O2 partial pressure was regulated at least lower than 5 mmHg ) for 8 h, then were recovered to normal culture environment. Apoptosis was detected with TUNEL. The activity of pyruvate dehydrogenase (PDH) and carnitine palmitoyltransferase 1 (CPT-1), the rate of glycose oxidation and glycolysis, and fatty acid metabolism were detected by liquid scintillation counting. The results are as follows: (1) The activity of active PDH (PDHa) was slightly higher in hypertrophic cardiomyocytes than that in normal cardiomyocytes, but the activity of CPT-1 was significantly lower in hypertrophic cardiomyoctes than that in normal cardiomyocytes.Compared with the hypertrophic cardiomyocytes cultured with normal oxygen concentration, the activities of PDHa and CPT-1 were decreased significantly after hypoxia for 8 h, and the activity of PDHa were decreased further after reoxygenation for 4 h, but the activity of CPT-1 recovered quickly after reoxygenation. (2) The rate of glucose oxidation in hypertrophic cardiomyocytes increased slightly when cultured under normal O2 partial pressure than that in normal cardiac cells. The rate of glucose oxidation reduced (16 +/- 0.9)% and (48 +/- 1.1)% in normal and hypertrophic cardiomyocytes, respectively, after hypoxia. It reduced further in hypertrophic cardiac cells at 4 h of reoxygenation, then recovered gradually. In normal cardiocytes, it recovered quickly after reoxygenation. (3) The rate of glycolysis of hypertrophic cardiocytes increased slightly than that of the normal cardiocytes when cultured in the general O(2) environment. Compared with the normal cardiomyocytes, the rate of glycolysis of hypertrophic cardiac cells was the same during hypoxia-reoxygenation culture, i.e., the rate of glycolysis decreased slightly after hypoxia for 8 h, but increased rapidly and significantly after reoxygenation. (4) The rate of fatty acid oxidation was slightly lower in hypertrophic cardiocytes than that in normal cardiomyocytes. After hypoxia for 8 h, the rate of fatty acid oxidation decreased significantly in normal and hypertrophic cardiomyocytes, there was no difference between normal and hypertrophic cardiomyocytes. But the alterations of fatty acid oxidation after reoxygenation were different between normal and hypertrophic cardiac cells, namely, the fatty acid oxidation of normal cardiomyocytes were activated slowly and slightly, while the rate of fatty acid oxidation of hypertrophic cardiomyocytes increased markedly at the early stage of reoxygenation, and increased further at 8 h of reoxygenation. (5) The rate of apoptosis in hypertrophic cardiocytes increased obviously after hypoxia for 8 h, and increased further and markedly at the early stage of reoxygenation, then gradually decreased to normal level. (6) Dicholoroacetate could inhibit apoptosis of hypertrophic cardiocytes through increasing glucose oxidation and inhibiting the activation of glycolysis and fatty acid oxidation of hypertrophic cardiomyocytes induced by hypoxia-reoxygenation. These data demonstrate that apoptosis in hypertrophic cardiomyocytes after hypoxia-reoxygenation is mainly due to the inhibition of glucose oxidation and the activation of glucolysis and fatty acid oxidation. Furthermore, increasing glucose oxidation may be a new pharmacotherapeutic target to inhibit apoptosis of hypertrophic cardiac cells.
authors.affiliation: Department of Kidney Disease, Xinqiao Hospital, the Third Military Medical University, Chongqing 400037, China. fxb12@yahoo.com.cn
authors.forename: Bing
authors.initials: B
authors.lastname: Feng
authors.forename: Wei
authors.initials: W
authors.lastname: Liu
authors.forename: Jing
authors.initials: J
authors.lastname: Xu
authors.forename: Zuo-Yun
authors.initials: ZY
authors.lastname: He
authors.forename: Hui-Biao
authors.initials: HB
authors.lastname: Yang
mesh_terms: D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D000831:Animals, Newborn; D017209:Apoptosis / Q000502:physiology*; D006332:Cardiomegaly / Q000473:pathology; D049108:Cell Enlargement / Q000187:drug effects; D015687:Cell Hypoxia; D004734:Energy Metabolism; D015428:Myocardial Reperfusion Injury / Q000378:metabolism* / Q000473:pathology; D032383:Myocytes, Cardiac / Q000378:metabolism* / Q000473:pathology*; D009638:Norepinephrine / Q000494:pharmacology; D010100:Oxygen / Q000378:metabolism*; D051381:Rats
chemical_list: D000804:Angiotensin II; D010100:Oxygen; D009638:Norepinephrine