Experimental biology and medicine
-
Exp. Biol. Med. (Maywood) · Dec 2011
Diet-induced obesity suppresses sevoflurane preconditioning against myocardial ischemia-reperfusion injury: role of AMP-activated protein kinase pathway.
Obesity is a major risk factor for coronary artery disease, but its impact on anesthetic-induced cardioprotective actions is unexplored. We tested whether obesity inhibits anesthetic sevoflurane-induced preconditioning and whether this effect is mediated via the AMP-activated protein kinase (AMPK) signaling pathway. Sprague-Dawley rats were fed a high-fat (HF, 45% kcal as fat) or low-fat (LF, 10% kcal as fat) diet for 12 weeks. ⋯ In addition, sevoflurane preconditioning failed to enhance reactive oxygen species (ROS) generation in the myocardium of HF-fed rats compared with LF-fed rats. Direct activation of AMPK with A769662 equally increased phosphorylation of AMPK and reduced infarct size in both LF- and HF-fed rats. The results suggest that diet-induced obesity suppresses sevoflurane preconditioning-induced cardioprotective action, probably due to a diminished effect of sevoflurane preconditioning on activation of the ROS-mediated AMPK signaling pathway.
-
Exp. Biol. Med. (Maywood) · Nov 2011
Honokiol, a chemopreventive agent against skin cancer, induces cell cycle arrest and apoptosis in human epidermoid A431 cells.
Honokiol is a plant lignan isolated from bark and seed cones of Magnolia officinalis. Recent studies from our laboratory indicated that honokiol pretreatment decreased ultraviolet B-induced skin cancer development in SKH-1 mice. The aim of the present investigation was to study the effects of honokiol on human epidermoid squamous carcinoma A431 cells and to elucidate possible mechanisms involved in preventing skin cancer. ⋯ Honokiol down-regulated the expression of cyclin D1, cyclin D2, Cdk2, Cdk4 and Cdk6 proteins and up-regulated the expression of Cdk's inhibitor proteins p21 and p27. Pretreatment of A431 cells with honokiol leads to induction of apoptosis and DNA fragmentation. These findings indicate that honokiol provides its effects in squamous carcinoma cells by inducing cell cycle arrest at G0/G1 phase and apoptosis.
-
Exp. Biol. Med. (Maywood) · Nov 2011
Possible involvement of uncoupling protein 1 in appetite control by leptin.
Leptin reduces body fat by decreasing food intake and increasing energy expenditure. Uncoupling protein (UCP) 1, a key molecule for brown adipose tissue (BAT) thermogenesis, was reported to contribute to the stimulatory effect of leptin on energy expenditure. To clarify whether UCP1 is also involved in the anorexigenic effect of leptin, in this study we examined the effect of leptin on food intake using wild-type (WT) and UCP1-deficient (UCP1-KO) mice. ⋯ Two-week treatment with CL enhanced the anorexigenic effect of leptin in WT mice, but not in UCP1-KO mice. Three-day treatment with CL in WT mice also enhanced the anorexigenic effect of leptin and leptin-induced phosphorylation of signal transducer and activator of transcription 3 (STAT3) in the arcuate nucleus of the hypothalamus, without any notable change in adiposity. These results indicate that UCP1 enhances leptin action at the hypothalamus level, suggesting UCP1 contributes to the control of energy balance not only through the regulation of energy expenditure but also through appetite control by modulating leptin action.
-
Exp. Biol. Med. (Maywood) · Oct 2011
High-frequency oscillatory ventilation attenuates oxidative lung injury in a rabbit model of acute lung injury.
Mechanical ventilation (MV) can induce lung oxidative stress, which plays an important role in pulmonary injury. This study compared protective conventional mechanical ventilation (CMV) and high-frequency oscillatory ventilation (HFOV) for oxygenation, oxidative stress, inflammatory and histopathological lung injury in a rabbit model of acute lung injury (ALI). Rabbits (n = 30) were ventilated at FiO(2) 1.0. ⋯ After four hours of ventilation, HFG showed better oxygenation (partial pressure of oxygen [PaO(2)] - CG: 465.9 ± 30.5 = HFG: 399.1 ± 98.2 > CMVG: 232.7 ± 104 mmHg, P < 0.05) and inflammatory responses (CMVG: 4.27 ± 1.50 > HFG: 0.33 ± 0.20 = CG: 0.16 ± 0.15; polymorphonuclear cells/bronchoalveolar lavage fluid/lung, P < 0.05), less histopathological injury score (CMVG: 5 [1-16] > HFG: 1 [0-5] > CG: 0 [0-3]; P < 0.05), and lower lung oxidative stress than CMVG (CG: 59.4 ± 4.52 = HFG: 69.0 ± 4.99 > CMVG: 47.6 ± 2.58% protection/g protein, P < 0.05). This study showed that HFOV had an important protective role in ALI. It improved oxygenation, reduced inflammatory process and histopathological damage, and attenuated oxidative lung injury compared with protective CMV under these experimental conditions considering the study limitations.
-
Exp. Biol. Med. (Maywood) · Nov 2010
Molecular signaling of pruritus induced by endothelin-1 in mice.
Endothelin-1 (ET-1) has recently been identified to evoke pruritus/itching sensation in both humans and animals. It is most likely that the signaling is through the specific G-protein-coupled ET(A) and ET(B) receptors, but the downstream signaling mediators for ET-1 remain elusive. In the present study, we examined the potential involvement of several distinct signaling molecules in ET-1-induced pruritus in a murine model. ⋯ In addition, the scratching response was significantly reduced by inhibitors for PKC and AC, but was significantly enhanced by PLC inhibitor, while PKA inhibitors showed no effects in the ET-1-induced scratching response. Our data suggested that ET-1 may signal through the ET(A) receptor, AC and PKC pathway to induce pruritus sensation, while ET(B) receptor and PLC may antagonize the pruritus evoked by ET-1. These results may provide a basis for the future development of antipruritic therapy.