• 한국생물공학회:학술대회논문집
• /
• 2005.10a
• /
• pp.296-296
• /
• 2005

• 한국생물공학회:학술대회논문집
• /
• 2005.10a
• /
• pp.870-870
• /
• 2005

• 한국생물공학회:학술대회논문집
• /
• 2005.10a
• /
• pp.910-910
• /
• 2005

• 한국생물공학회:학술대회논문집
• /
• 2005.10a
• /
• pp.295-295
• /
• 2005

• Journal of Yeungnam Medical Science
• /
• v.34 no.1
• /
• pp.19-28
• /
• 2017

The incidence of type 2 diabetes mellitus and insulin resistance is growing rapidly. Multiple organs including the liver, skeletal muscle and adipose tissue control insulin sensitivity coordinately, but the mechanism of skeletal muscle insulin resistance has not yet been fully elucidated. However, there is a growing body of evidence that lipotoxicity induced by mitochondrial dysfunction in skeletal muscle is an important mediator of insulin resistance. However, some recent findings suggest that skeletal mitochondrial dysfunction generated by genetic manipulation is not always correlated with insulin resistance in animal models. A high fat diet can provoke insulin resistance despite a coordinate increase in skeletal muscle mitochondria, which implies that mitochondrial dysfunction is not mandatory in insulin resistance. Furthermore, incomplete fatty acid oxidation by excessive nutrition supply compared to mitochondrial demand can induce insulin resistance without preceding impairment of mitochondrial function. Taken together we suggested that skeletal muscle mitochondrial overloading, not mitochondrial dysfunction, plays a pivotal role in insulin resistance.

• The Korean Journal of Physiology and Pharmacology
• /
• v.20 no.2
• /
• pp.201-211
• /
• 2016

Although the antioxidant and cardioprotective effects of NecroX-5 on various in vitro and in vivo models have been demonstrated, the action of this compound on the mitochondrial oxidative phosphorylation system remains unclear. Here we verify the role of NecroX-5 in protecting mitochondrial oxidative phosphorylation capacity during hypoxia-reoxygenation (HR). Necrox-5 treatment ($10{\mu}M$) and non-treatment were employed on isolated rat hearts during hypoxia/reoxygenation treatment using an ex vivo Langendorff system. Proteomic analysis was performed using liquid chromatography-mass spectrometry (LC-MS) and non-labeling peptide count protein quantification. Real-time PCR, western blot, citrate synthases and mitochondrial complex activity assays were then performed to assess heart function. Treatment with NecroX-5 during hypoxia significantly preserved electron transport chain proteins involved in oxidative phosphorylation and metabolic functions. NecroX-5 also improved mitochondrial complex I, II, and V function. Additionally, markedly higher peroxisome proliferator-activated receptor-gamma coactivator-$1{\alpha}$ ($PGC1{\alpha}$) expression levels were observed in NecroX-5-treated rat hearts. These novel results provide convincing evidence for the role of NecroX-5 in protecting mitochondrial oxidative phosphorylation capacity and in preserving $PGC1{\alpha}$ during cardiac HR injuries.

• The Korean Journal of Physiology and Pharmacology
• /
• v.11 no.2
• /
• pp.57-64
• /
• 2007

Ischemic preconditioning (IPC) is known to protect the heart against ischemia/reperfusion (IR)-induced injuries, and regional differences in the mitochondrial antioxidant state during IR or IPC may promote the death or survival of viable and infarcted cardiac tissues under oxidative stress. To date, however, the interplay between the mitochondrial antioxidant enzyme system and the level of reactive oxygen species (ROS) in the body has not yet been resolved. In the present study, we examined the effects of IR- and IPC-induced oxidative stresses on mitochondrial function in viable and infarcted cardiac tissues. Our results showed that the mitochondria from viable areas in the IR-induced group were swollen and fused, whereas those in the infarcted area were heavily damaged. IPC protected the mitochondria, thus reducing cardiac injury. We also found that the activity of the mitochondrial antioxidant enzyme system, which includes manganese superoxide dismutase (Mn-SOD), was enhanced in the viable areas compared to the infarcted areas in proportion with decreasing levels of ROS and mitochondrial DNA (mtDNA) damage. These changes were also present between the IPC and IR groups. Regional differences in Mn-SOD expression were shown to be related to a reduction in mtDNA damage as well as to the release of mitochondrial cytochrome c (Cyt c). To the best of our knowledge, this might be the first study to explore the regional mitochondrial changes during IPC. The present findings are expected to help elucidate the molecular mechanism involved in IPC and helpful in the development of new clinical strategies against ischemic heart disease.

• BMB Reports
• /
• v.48 no.10
• /
• pp.571-576
• /
• 2015

SB743921 is a potent inhibitor of the spindle protein kinesin and is being investigated in ongoing clinical trials for the treatment of myeloma. However, little is known about the molecular events underlying the induction of cell death in multiple myeloma (MM) by SB743921, alone or in combination treatment. Here, we report that SB743921 induces mitochondria-mediated cell death via inhibition of the $NF-{\kappa}B$ signaling pathway, but does not cause cell cycle arrest in KMS20 MM cells. SB743921-mediated inhibition of the $NF-{\kappa}B$ pathway results in reduced expression of SOD2 and Mcl-1, leading to mitochondrial dysfunction. We also found that combination treatment with SB743921 and bortezomib induces death in bortezomib-resistant KMS20 cells. Altogether, these data suggest that treatment with SB743921 alone or in combination with bortezomib offers excellent translational potential and promises to be a novel MM therapy.

• BMB Reports
• /
• v.52 no.2
• /
• pp.109-110
• /
• 2019

Mitochondrial morphology is known to be continuously changing via fusion and fission, but it is unclear what the biological importance of this energy-consuming process is and how it develops. Several data have suggested that mitochondrial fission executed by Drp1 is necessary to select out a damaged spot from the interconnected mitochondrial network, but the precise mechanism for the recognition and isolation of a damaged sub-mitochondrial region during mitochondrial fission is yet unclear. Recently, Cho et al. found that the mitochondrial membrane potential (MMP) is transiently reduced by the physical interaction of Drp1 and mitochondrial Zinc transporter, Zip1, at the fission site prior to the typical mitochondrial division, and we found that this event is essential for a mitochondrial quality surveillance. In this review, Cho et al. discuss the role of a mitochondrial fission in the mitochondrial quality surveillance system.

• The Korean Journal of Physiology and Pharmacology
• /
• v.9 no.5
• /
• pp.291-298
• /
• 2005

To characterize cytosolic $Ca^{2+}$ fluctuations under metabolic inhibition, rat ventricular myocytes were exposed to $200{\mu}M$ 2,4-dinitrophenol (DNP), and mitochondrial $Ca^{2+}$, mitochondrial membrane potential (${\Delta}{\Psi}m$), and cytosolic $Ca^{2+}$ were measured, using Rhod-2 AM, TMRE, and Fluo-4 AM fluorescent dyes, respectively, by Laser Scanning Confocal Microscopy (LSCM). Furthermore, the role of sarcolemmal $Na^+$/$Ca^{2+}$ exchange (NCX) in cytosolic $Ca^{2+}$ efflux was studied in KB-R7943 and $Na^+$-free normal Tyrode's solution (143 mM LiCl ). When DNP was applied to cells loaded with Fluo-4 AM, Fluo-4 AM fluorescence intensity initially increased by $70{\pm}10$% within $70{\pm}10$ s, and later by $400{\pm}200$% at $850{\pm}45$ s. Fluorescence intensity of both Rhod-2 AM and TMRE were initially decreased by DNP, coincident with the initial increase of Fluo-4 AM fluorescence intensity. When sarcoplasmic reticulum (SR) $Ca^{2+}$ was depleted by $1{\mu}M thapsigargin plus $10{\mu}M ryanodine, the initial increase of Fluo-4 AM fluorescence intensity was unaffected, however, the subsequent progressive increase was abolished. KB-R7943 delayed both the first and the second phases of cytosolic $Ca^{2+}$ overload, while $Na^+$-free solution accelerated the second. The above results suggest that: 1) the initial rise in cytosolic $Ca^{2+}$ under DNP results from mitochondrial depolarization; 2) the secondary increase is caused by progressive $Ca^{2+}$ release from SR; 3) NCX plays an important role in transient cytosolic $Ca^{2+}$ shifts under metabolic inhibition with DNP.