To explore the role of histone deactylase (HDAC) activation in an in vivo model of hypertrophy, we studied the effects of Trichostatin A (TSA). TSA subjected to thoracic aortic banding (TAB)-induced pressure stress in mice. In histological observations, TAB in treated mice showed a significant hypertrophic response, whereas the sham operation remained nearly normal structure with partially blunted hypertrophy. TSA treatment had no effect (measured as HW/BW) on sham-operated animals. TAB animals treated with vehicle manifested a robust ～50% hypertrophic response (p<0.05 vs sham). TAB mice treated with 2 mg/kg/day TSA manifested a blunted growth responses, which was significantly diminished (p<0.05) compared with vehicle-treated TAB mice. TAB mice treated with a lower dose of TSA (0.5 mg/kg/day) manifested a similar blunting of hypertrophic growth (～25% increase in heart mass). Furthermore, to determine activity duration of TSA in vitro, 1 nM TSA was added to H9c2 cells. Histone acetylation was initiated at 4 hr after treatment, and it was peak up to 18 hr, then followed by significantly reduced to 30 hr. We also analyzed the expression of p53 following TSA treatment, wherein p53 expression was elevated at 4 hr, and it was maintained to 24 hr after treatment. ERK was activated at 8 hr, and maintained till 30 hr after treatment suggesting an intracellular signaling interaction between TSA and p53 expression. Taken together, it is suggested that HDAC activation is required for pressure-overload growth of the heart. Eventually, these data suggest that histone acetylation may be a novel target for therapeutic intervention in pressure-overloaded cardiac hypertrophy.

Clinical arthritis is typically divided into rheumatoid arthritis (RA) and osteoarthritis (OA). Arthritis-induced muscle weakness is a major problem in aged people, leading to a disturbance of balance during the gait cycle and frequent falls. The purposes of the present study were to confirm fiber type-dependent expression of muscle atrophy markers induced by arthritis and to identify the relationship between clinical signs and expression of muscle atrophy markers. Mice were divided into four experimental groups as follows: (1) negative control (normal), (2) positive control (CFA+acetic acid), (3) RA group (CFA+acetic acid+type Ⅱ collagen), and (4) aging-induced OA group. DBA/1J mice (8 weeks of age) were injected with collagen (50 μg/kg), and physiological (body weight) and pathological (arthritis score and paw thickness) parameters were measured once per week. The gastrocnemius muscle from animals in each group was removed, and the expression of muscle atrophy markers (MAFbx and MuRF1) and myosin heavy chain isoforms were analyzed by reverse transcription-polymerase chain reaction. No significant change in body weight occurred between control groups and collagen-induced RA mice at week 10. However, bovine type Ⅱ collagen induced a dramatic increase in clinical score or paw thickness at week 10 (p<0.01). Concomitantly, the expression of the muscle atrophy marker MAFbx was upregulated in the RA and OA groups (p<0.01). A dramatic reduction in myosin heavy chain (MHC)-Iβ was seen in the gastrocnemius muscles from RA and OA mice, while only a slight decrease in MHC-Ⅱb was seen. These results suggest that muscle atrophy gene expression occurred in a fiber type-specific manner in both RA- and OA-induced mice. The present study suggests evidence regarding why different therapeutic interventions are required between RA and OA.

Our objective of current study was to investigate the development of bone and heart in association with diabetes mellitus (DM). DM was induced by administering an intraperitoneal injection of streptozotocin (STZ; 60 mg/kg) to 4‐gweek‐gold Sprague‐gDawley rats. Body weight and blood glucose were monitored, and rats were sacrificed after 2 or 5 weeks. The left ventricle (LV), including the interventricular septum, was weighed, and body weight and tibial bone length were assessed. Young diabetic rats showed reduced growth in terms of tibial length and body weight compared to controls. Moreover, diabetic males showed more significant growth suppression and reduced LV size than diabetic females. Morphometric analysis of tibiae from diabetic rats revealed suppressed bone growth at 2 and 5 weeks, with no difference between genders. STZ‐ginduced diabetes decreased bone growth and retarded pre‐gpubertal heart development. As a result, diabetes may increase cardiovascular risk factors and lead to eventual heart failure. Therefore, new therapeutic approaches are required for diabetic children exhibiting growth retardation. Heart growth factor, exercise, and cardiopulmonary physical therapy may be required to promote heart development and physiological function.

Many biological systems are regulated by an intricate set of feedback loops that oscillate with a circadian rhythm of roughly 24 h. This circadian clock mediates an increase in body temperature, heart rate, blood pressure, and cortisol secretion early in the day. Recent studies have shown changes in the amplitude of the circadian clock in the hearts and livers of streptozotocin (STZ)-treated rats. It is therefore important to examine the relationships between circadian clock genes and growth factors and their effects on diabetic phenomena in animal models as well as in human patients. In this study, we sought to determine whether diurnal variation in organ development and the regulation of metabolism, including growth and development during the juvenile period in rats, exists as a mechanism for anticipating and responding to the environment. Also, we examined the relationship between changes in growth factor expression in the liver and clock-controlled protein synthesis and turnover, which are important in cellular growth. Specifically, we assessed the expression patterns of several clock genes, including Per1, Per2, Clock, Bmal1, Cry1 and Cry2 and growth factors such as insulin-like growth factor (IGF)-1 and -2 and transforming growth factor (TGF)-β1 in rats with STZ-induced diabetes. Growth factor and clock gene expression in the liver at 1 week post-induction was clearly increased compared to the level in control rats. In contrast, the expression patterns of the genes were similar to those observed after 5 weeks in the STZ-treated rats. The increase in gene expression is likely a compensatory change in response to the obstruction of insulin function during the initial phase of induction. However, as the period of induction was extended, the expression of the compensatory genes decreased to the control level. This is likely the result of decreased insulin secretion due to the destruction of beta cells in the pancreas by STZ.

본 실험은 polyethylene glycol (PEG)에 용해시킨 FSH의 투여 방법과 용량에 따른 체내 수정란 생산 효율을 난소 반응과 회수되는 수정란의 수량과 품질, 수정란 이식 효율을 조사하였다. 공란우 88마리를 네 군으로 구분하였다. 처리 1군은 50 mg의 FSH를 하루 2회 4일 동안 투여하였으며, 처리 2 및 3군은 30% PEG 에 녹인 400 mg과 200 mg의 FSH 용량을 1회 투여하였으며, 처리 4군은 CIDR로 처리 후 7일째에 30% PEG에 녹인 200 mg의 FSH를 처리하였다. 과배란 처리 후 황체수에서는 처리 1, 2, 3 및 4군에서 각각 11.2, 18.5, 13.1 및 13.9개로서, 처리 2군에서 다른 처리군보다 유의적으로(p<0.05) 높았다. 회수된 난자의 총 수에서 각 군의 결과는 8.5, 10.4, 8.7 및 7.9개였으며, 이식 가능한 수정란 수에서 각 군의 결과는 3.9, 4.3, 4.7 및 3.7개로 군간의 유의적인 차이는 보이지 않았다. 각 과배란 처리 방법에 따라 생산된 수정란의 이식 후 수태율 (36.0～50.0%) 및 채란시 혈중 progesterone 농도 또한 군간의 유의적인 차이는 보이지 않았다. 결론적으로 공란우에 스트레스를 적게 주며 과배란 처리 호르몬 비용과 노동력을 줄일 수 있으며, 여러 마리의 공란우를 발정 주기에 상관없이 한 번에 과배란 처리를 할 수 있는 CIDR를 사용 후 7일째 200 mg의 FSH를 1회 투여 방법이 축산 현장에서 적용하기에 매우 유용한 방법이라 사료된다.