• Molecules and Cells
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• 제43권1호
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• pp.66-75
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• 2020

Saturated fatty acids contribute to β-cell dysfunction in the onset of type 2 diabetes mellitus. Cellular responses to lipotoxicity include oxidative stress, endoplasmic reticulum (ER) stress, and blockage of autophagy. Palmitate induces ER Ca²⁺ depletion followed by notable store-operated Ca²⁺ entry. Subsequent elevation of cytosolic Ca²⁺ can activate undesirable signaling pathways culminating in cell death. Mitochondrial Ca²⁺ uniporter (MCU) is the major route for Ca²⁺ uptake into the matrix and couples metabolism with insulin secretion. However, it has been unclear whether mitochondrial Ca²⁺ uptake plays a protective role or contributes to lipotoxicity. Here, we observed palmitate upregulated MCU protein expression in a mouse clonal β-cell, MIN6, under normal glucose, but not high glucose medium. Palmitate elevated baseline cytosolic Ca²⁺ concentration ([Ca²⁺]_i) and reduced depolarization-triggered Ca²⁺ influx likely due to the inactivation of voltage-gated Ca²⁺ channels (VGCCs). Targeted reduction of MCU expression using RNA interference abolished mitochondrial superoxide production but exacerbated palmitate-induced [Ca²⁺]_i overload. Consequently, MCU knockdown aggravated blockage of autophagic degradation. In contrast, co-treatment with verapamil, a VGCC inhibitor, prevented palmitate-induced basal [Ca²⁺]_i elevation and defective [Ca²⁺]_i transients. Extracellular Ca²⁺ chelation as well as VGCC inhibitors effectively rescued autophagy defects and cytotoxicity. These observations suggest enhanced mitochondrial Ca²⁺ uptake via MCU upregulation is a mechanism by which pancreatic β-cells are able to alleviate cytosolic Ca²⁺ overload and its detrimental consequences.

• 한국생물공학회:학술대회논문집
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• 한국생물공학회 2005년도 생물공학의 동향(XVII)
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• pp.870-870
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• 2005

• Asian-Australasian Journal of Animal Sciences
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• 제29권11호
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• pp.1585-1592
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• 2016

The present experiment was conducted to evaluate the effect of simulated heat stress on digestibility and methane ($CH_4$) emission. Four non-lactating crossbred cattle were exposed to $25^{\circ}C$, $30^{\circ}C$, $35^{\circ}C$, and $40^{\circ}C$ temperature with a relative humidity of 40% to 50% in a climatic chamber from 10:00 hours to 15:00 hours every day for 27 days. The physiological responses were recorded at 15:00 hours every day. The blood samples were collected at 15:00 hours on 1st, 6th, 11th, 16th, and 21st days and serum was collected for biochemical analysis. After 21 days, fecal and feed samples were collected continuously for six days for the estimation of digestibility. In the last 48 hours gas samples were collected continuously to estimate $CH_4$ emission. Heat stress in experimental animals at $35^{\circ}C$ and $40^{\circ}C$ was evident from an alteration (p<0.05) in rectal temperature, respiratory rate, pulse rate, water intake and serum thyroxin levels. The serum lactate dehydrogenase, aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase activity and protein, urea, creatinine and triglyceride concentration changed (p<0.05), and body weight of the animals decreased (p<0.05) after temperature exposure at $40^{\circ}C$. The dry matter intake (DMI) was lower (p<0.05) at $40^{\circ}C$ exposure. The dry matter and neutral detergent fibre digestibilities were higher (p<0.05) at $35^{\circ}C$ compared to $25^{\circ}C$ and $30^{\circ}C$ exposure whereas, organic matter (OM) and acid detergent fibre digestibilities were higher (p<0.05) at $35^{\circ}C$ than $40^{\circ}C$ thermal exposure. The $CH_4$ emission/kg DMI and organic matter intake (OMI) declined (p<0.05) with increase in exposure temperature and reached its lowest levels at $40^{\circ}C$. It can be concluded from the present study that the digestibility and $CH_4$ emission were affected by intensity of heat stress. Further studies are necessary with respect to ruminal microbial changes to justify the variation in the digestibility and $CH_4$ emission during differential heat stress.

• The Korean Journal of Physiology and Pharmacology
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• 제15권3호
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• pp.171-177
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• 2011

Tonic smooth muscle exhibit the latch phenomenon: high force at low myosin regulatory light chains (MRLC) phosphorylation, shortening velocity (Vo), and energy consumption. However, the kinetics of MRLC phosphorylation and cellular activation in phasic smooth muscle are unknown. The present study was to determine whether $Ca^{2+}$-stimulated MRLC phosphorylation could suffice to explain the agonist- or high $K^+$-induced contraction in a fast, phasic smooth muscle. We measured myoplasmic [$Ca^{2+}$], MRLC phosphorylation, half-time after step-shortening (a measure of Vo) and contractile stress in rabbit urinary bladder strips. High $K^+$-induced contractions were phasic at both $22^{\circ}C$ and $37^{\circ}C$: myoplasmic [$Ca^{2+}$], MRLC phosphorylation, 1/half-time, and contractile stress increased transiently and then all decreased to intermediate values. Carbachol (CCh)-induced contractions exhibited latch at $37^{\circ}C$: stress was maintained at high levels despite decreasing myoplasmic [$Ca^{2+}$], MRLC phosphorylation, and 1/half-time. At $22^{\circ}C$ CCh induced sustained elevations in all parameters. 1/half-time depended on both myoplasmic [$Ca^{2+}$] and MRLC phosphorylation. The steady-state dependence of stress on MRLC phosphorylation was very steep at $37^{\circ}C$ in the CCh- or $K^+$-depolarized tissue and reduced temperature flattend the dependence of stress on MRLC phosphorylation compared to $37^{\circ}C$. These data suggest that phasic smooth muscle also exhibits latch behavior and latch is less prominent at lower temperature.

• The Korean Journal of Physiology and Pharmacology
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• 제22권3호
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• pp.257-267
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• 2018

The present study aimed to evaluate the cinnamic acid effect on memory impairment, oxidative stress, and cholinergic dysfunction in streptozotocin (STZ)-induced diabetic model in mice. In this experimental study, 48 male Naval Medical Research Institute (NMRI) mice (30-35 g) were chosen and were randomly divided into six groups: control, cinnamic acid (20 mg/kg day, i.p.), diabetic, and cinnamic acid-treated diabetic (10, 20 and 40 mg/kg day, i.p.). Memory was impaired by administering an intraperitoneal STZ injection of 50 mg/kg. Cinnamic acid was injected for 40 days starting from the 21st day after confirming STZ-induced dementia to observe its therapeutic effect. Memory function was assessed using cross-arm maze, morris water maze and passive avoidance test. After the administration, biochemical parameters of oxidative stress and cholinergic function were estimated in the brain. Present data indicated that inducing STZ caused significant memory impairment, whereas administration of cinnamic acid caused significant and dose-dependent memory improvement. Assessment of brain homogenates indicated cholinergic dysfunction, increase in lipid peroxidation and reactive oxygen species (ROS) levels, and decrease in glutathione (GSH), superoxide dismutase (SOD), and catalase (CAT) activities in the diabetic group compared to the control animals, whereas cinnamic acid administration ameliorated these indices in the diabetic mice. The present study demonstrated that cinnamic acid improves memory by reducing the oxidative stress and cholinergic dysfunction in the brain of diabetic mice.

• 대한약침학회지
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• 제22권2호
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• pp.109-114
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• 2019

Objectives: Oxidative stress plays a central role in diabetes-induced complications. In the present study, the protevtive effect of Artemisia turanica (A. turanica) was evaluated against diabetes-induced liver oxidative stress and dysfunction. Methods: Fifty male Wistar rats were randomly divided into five groups: control, diabetic, diabetic + metformin, diabetic + A. turanica extract, and diabetic + A. turanica extract + metformin. Experimental diabetes was induced by a single-dose (55 mg/kg, intraperitoneally (ip)) injection of streptozotocin (STZ). Metformin (300 mg/kg) and A. turanica extract (70 mg/kg) were orally administrated three days after STZ injection for four weeks. The levels of malondialdehyde (MDA), total thiol content and superoxide dismutase (SOD) and catalase activities were measured in the liver tissue. Serum glucose concentration, aspartate aminotransferase (AST) and alanine aminotransferase (ALT) activities were also determined. Results: In the diabetic group, serum glucose concentration, serum AST and ALT activities and liver MDA level were significantly higher while tissue total thiol content as well as catalase and SOD activities were lower, compared to the control group. Serum glucose in diabetic rats treated with metformin + A. turanica extract showed a significant decrease compared with the diabetic group. In all the A. turanica extract and metformin treated groups, serum ALT, tissue MDA level, total thiol content and SOD activity significantly improved compared with the diabetic rats. However, treatment of the diabetic rats only with metformin could not significantly change the activities of catalase and AST compared with the diabetic group. Conclusion: These findings suggested that A. turanica extract had a therapeutic effect on liver dysfuncyion and oxidative stress induced by diabetes, that may be probably due to its antioxidant and antiinflammatory effects.

• Molecules and Cells
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• 제26권3호
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• pp.243-249
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• 2008

Corticotropin releasing factor (CRF) mediates various responses to stress through CRF receptors 1 and 2. CRF receptor 2 has two forms, $2{\alpha}$ and $2{\beta}$ each of which appears to have distinct roles. Here we used dopaminergic neuron-derived MN9D cells to investigate the function of CRF receptor 2 in dopamine neurons. We found that n-butyrate, a histone deacetylase inhibitor, induced MN9D cell differentiation and increased gene expression of all CRF receptors. CRF receptor $2{\beta}$ was minimally expressed in MN9D cells; however, its expression dramatically increased during differentiation. CRF receptor $2{\beta}$ expression levels appeared to correlate with neurite outgrowth, suggesting CRF receptor $2{\beta}$ involvement in neuronal differentiation. To validate this statement, we made a CRF receptor $2{\beta}$-overexpressing $MN9D/CRFR2{\beta}$ stable cell line. This cell line showed robust neurite outgrowth and GAP43 overexpression, together with MEK and ERK activation, suggesting MN9D cell neuronal differentiation. From these results, we conclude that CRF receptor $2{\beta}$ plays an important role in MN9D cell differentiation by activating the MEK/ERK signaling pathway.

• International Journal of Oral Biology
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• 제33권1호
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• pp.7-12
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• 2008

PG has been well studied about effects of stress resistance. Although ZJ has been known that it had stress resistance effect since ancient times, its pharmacological properties and clinical applications have not been studied and reported until recently. Therefore, the purpose of this study is to determine whether effects of stress hormones, mechanism of stress protein could be induced by PG and ZJ of herb extract ingestion during stress exposure. In addition, this study identified expression of apoptosis factors related to stress. 1) Bcl-2 expression of the stressed rats decreased in comparison with the unstressed rats in heart and stomach. Bcl-2 expression of rats administered to PG was higher than the stressed rats in heart and that of rats administered to ZJ was higher than the stressed rats in stomach. 2) Stressed rats were decreased in p53 protein expression than normal rats. Thus, the results suggest stress-induced apoptosis is p53-independent apoptosis. And these results demonstrated that PG or ZJ administration helped to return from stress state to normal. 3) Clusterin expressed markedly in only salivary gland, but that of expression was no difference among four groups in tissues. Clusterin expression has no relation of stress-induced apoptosis.

• The Korean Journal of Physiology and Pharmacology
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• 제22권5호
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• pp.567-575
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• 2018

Acute kidney injury (AKI), which is defined as a rapid decline of renal function, becomes common and recently recognized to be closely intertwined with chronic kidney diseases. Current treatment for AKI is largely supportive, and endoplasmic reticulum (ER) stress has emerged as a novel mediator of AKI. Since carbon monoxide attenuates ER stress, the objective of the present study aimed to determine the protective effect of carbon monoxide releasing molecule-2 (CORM2) on AKI associated with ER stress. Kidney injury was induced after LPS (15 mg/kg) treatment at 12 to 24 h in C57BL/6J mice. Pretreatment of CORM2 (30 mg/kg) effectively prevented LPS-induced oxidative stress and inflammation during AKI in mice. CORM2 treatment also effectively inhibited LPS-induced ER stress in AKI mice. In order to confirm effect of CO on the pathophysiological role of tubular epithelial cells in AKI, we used mProx24 cells. Pretreatment of CORM2 attenuated LPS-induced ER stress, oxidative stress, and inflammation in mProx24 cells. These data suggest that CO therapy may prevent ER stress-mediated AKI.

• Journal of Microbiology and Biotechnology
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• 제19권6호
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• pp.547-555
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• 2009

Nanoscopic changes in the cell surface morphology of the yeasts Saccharomyces cerevisiae (strain NCYC 1681) and Schizosaccharomyces pombe (strain DVPB 1354), due to their exposure to varying concentrations of hydrogen peroxide (oxidative stress), were investigated using an atomic force microscope (AFM). Increasing hydrogen peroxide concentration led to a decrease in cell viabilities and mean cell volumes, and an increase in the surface roughness of the yeasts. In addition, AFM studies revealed that oxidative stress caused cell compression in both S. cerevisiae and Schiz. pombe cells and an increase in the number of aged yeasts. These results confirmed the importance and usefulness of AFM in investigating the morphology of stressed microbial cells at the nanoscale. The results also provided novel information on the relative oxidative stress tolerance of S. cerevisiae and Schizo pombe.