• Journal of Ginseng Research
• /
• v.47 no.5
• /
• pp.615-621
• /
• 2023

Korean Red Ginseng (KRG) plays a key role in heme oxygenase (HO)-1 induction under physical and moderate oxidative stress conditions. The transient and mild induction of HO-1 is beneficial for cell protection, mitochondrial function, regeneration, and intercellular communication. However, chronic HO-1 overexpression is detrimental in severely injured regions. Thus, in a chronic pathological state, diminishing HO-1-mediated ferroptosis is beneficial for a therapeutic approach. The molecular mechanisms by which KRG protects various cell types in the central nervous system have not yet been established, especially in terms of HO-1-mediated mitochondrial functions. Therefore, in this review, we discuss the multiple roles of KRG in the regulation of astrocytic HO-1 under pathophysiological conditions. More specifically, we discuss the role of the KRG-mediated astrocytic HO-1 pathway in regulating mitochondrial functions in acute and chronic neurodegenerative diseases as well as physiological conditions.

• BMB Reports
• /
• v.43 no.4
• /
• pp.225-232
• /
• 2010

Parkinson's Disease (PD) is a common neurodegenerative disease characterized by the progressive degeneration of nigrostriatal dopaminergic (DA) neurons. Although the causative factors of PD remain elusive, many studies on PD animal models or humans suggest that glial activation along with neuroinflammatory processes contribute to the initiation or progression of PD. Additionally, several groups have proposed that dysfunction of the blood-brain barrier (BBB) combined with infiltration of peripheral immune cells play important roles in the degeneration of DA neurons. However, these neuroinflammatory events have only been investigated separately, and the issue of whether these phenomena are neuroprotective or neurotoxic remains controversial. We here review the current knowledge regarding the functions of these neuroinflammatory processes in the brain. Finally, we describe therapeutic strategies for the regulation of neuroinflammation with the goal of improving the symptoms of PD.

• Molecular & Cellular Toxicology
• /
• v.5 no.2
• /
• pp.99-107
• /
• 2009

Naphthalene is bicyclic aromatic compound that is widely used in various domestic and commercial applications including lavatory scent disks, soil fumigants and moth balls. Exposure to naphthalene results in the development of bronchiolar damage, cataracts and hemolytic anemia in humans and laboratory animals. However, little information is available regarding the mechanism of naphthalene toxicity. We investigated gene expression profiles and potential signature genes in human hepatocellular carcinoma HepG2 cells and human promyelocytic leukemia HL-60 cells after 3 h and 48 h incubation with the IC$_{20}$ and IC$_{50}$ of naphthalene by using 44 k agilent whole human genome oligomicroarray and operon human whole 35 k oligomicroarray, respectively. We identified 616 up-regulated genes and 2,088 down-regulated genes changed by more than 2-fold by naphthalene in HepG2 cells. And in HL-60, we identified 138 up-regulated genes and 182 down-regulated genes changed by more than 2-fold. This study identified several interesting targets and functions in relation to naphthalene-induced toxicity through a gene ontology analysis method. Apoptosis and cell cycle related genes are more commonly expressed than other functional genes in both cell lines. In summary, the use of in vitro models with global expression profiling emerges as a relevant approach toward the identification of biomarkers associated with toxicity after exposure to a variety of environmental toxicants.

• Molecules and Cells
• /
• v.24 no.2
• /
• pp.210-214
• /
• 2007

The 90-kDa heat shock protein (HSP90) normally functions as a molecular chaperone participating in folding and stabilizing newly synthesized proteins, and refolding denatured proteins. The HSP90 inhibitor geldanamycin (GA) occupies the ATP/ADP binding pocket of HSP90 so inhibits its chaperone activity and causes subsequent degradation of HSP90 client proteins by proteasomes. Here we show that GA reduces the level of endogenous c-Jun in human embryonic kidney 293 (HEK293) cells in a time and dose dependent manner, and that this decrease can be reversed by transfection of HSP90 plasmids. Transfection of HSP90 plasmids in the absence of GA increases the level of endogenous c-Jun protein, but has no obvious affect on c-Jun mRNA levels. We also showed that HSP90 prolongs the half-life of c-Jun by stabilizing the protein; the proteasome inhibitor N-benzoyloxycarbonyl (Z)-Leu-Leu-leucinal (MG132) blocks the degradation of c-Jun promoted by GA. Transfection of HSP90 plasmids did not obviously alter phosphorylation of c-Jun, and a Jun-2 luciferase activity assay indicated that over-expression of HSP90 elevated the total protein activity of c-Jun in HEK293 cells. All our evidence indicates that HSP90 stabilizes c-Jun protein, and so increases the total activity of c-Jun in HEK293 cells.

• Journal of Life Science
• /
• v.18 no.4
• /
• pp.488-493
• /
• 2008

Phosphate, a favorable phosphorous form for plant, is one of major nutrient elements for growth and development in plants. Plants exhibit various physiological and biochemical responses in reaction to phosphate starvation in order to maintain phosphate homeostasis. Of them, expression of high affinity phosphate transporter gene family and efficient uptake of phosphate via them is a major physiological process for adaption to phosphate deficient environment. Although the various genetic resources of high affinity phosphate transporter are identified recently, little is known about their functions in plant that is prerequisite information before applying to crop plants to generate valuable transgenic plants. We demonstrated that Arabidopsis transgenic plants over-expressing two different high affinity phosphate transporter gens, OsPT1 and OsPT7, derived from rice, exhibit better growth responses compared with wild-type under phosphate starvation condition. Specially, OsPT7 gene has proven to be more effective to generate Arabidopsis transgenic plant tolerant to phosphate deficiency than OsPT1. Furthermore, the expression level of AtPT1 gene that is one of reporter genes specifically induced by phosphate starvation was significantly low compared with wild-type during phosphate starvation. Taken together, these results collectively suggest that over expression of OsPTl and OsPT7 genes derived from monocotyledonous plant function efficiently in the dicotyledonous plant, relieving stress response caused by phosphate starvation and leading to better growth rate.

• Journal of Ginseng Research
• /
• v.46 no.3
• /
• pp.408-417
• /
• 2022

Background: Korean Red Ginseng extract (KRGE) has been used as a health supplement and herbal medicine. Astrocytes are one of the key cells in the central nervous system (CNS) and have bioenergetic potential as they stimulate mitochondrial biogenesis. They play a critical role in connecting the brain vasculature and nerves in the CNS. Methods: Brain samples from KRGE-administered mice were tested using immunohistochemistry. Treatment of human brain astrocytes with KRGE was subjected to assays such as proliferation, cytotoxicity, Mitotracker, ATP production, and O₂ consumption rate as well as western blotting to demonstrate the expression of proteins related to mitochondria functions. The expression of hypoxia-inducible factor-1α (HIF-1α) was diminished utilizing siRNA transfection. Results: Brain samples from KRGE-administered mice harbored an increased number of GFAP-expressing astrocytes. KRGE triggered the proliferation of astrocytes in vitro. Enhanced mitochondrial biogenesis induced by KRGE was detected using Mitotracker staining, ATP production, and O₂ consumption rate assays. The expression of proteins related to mitochondrial electron transport was increased in KRGE-treated astrocytes. These effects were blocked by HIF-1α knockdown. The factors secreted from KRGE-treated astrocytes were determined, revealing the expression of various cytokines and growth factors, especially those related to angiogenesis and neurogenesis. KRGE-treated astrocyte conditioned media enhanced the differentiation of adult neural stem cells into mature neurons, increasing the migration of endothelial cells, and these effects were reduced in the background of HIF-1α knockdown. Conclusion: Our findings suggest that KRGE exhibits prophylactic potential by stimulating astrocyte mitochondrial biogenesis through HIF-1α, resulting in improved neurovascular function.

• BMB Reports
• /
• v.45 no.11
• /
• pp.612-622
• /
• 2012

Olfactory receptors (ORs) detect volatile chemicals that lead to the initial perception of smell in the brain. The olfactory receptor (OR) is the first protein that recognizes odorants in the olfactory signal pathway and it is present in over 1,000 genes in mice. It is also the largest member of the G protein-coupled receptors (GPCRs). Most ORs are extensively expressed in the nasal olfactory epithelium where they perform the appropriate physiological functions that fit their location. However, recent whole-genome sequencing shows that ORs have been found outside of the olfactory system, suggesting that ORs may play an important role in the ectopic expression of non-chemosensory tissues. The ectopic expressions of ORs and their physiological functions have attracted more attention recently since MOR23 and testicular hOR17-4 have been found to be involved in skeletal muscle development, regeneration, and human sperm chemotaxis, respectively. When identifying additional expression profiles and functions of ORs in non-olfactory tissues, there are limitations posed by the small number of antibodies available for similar OR genes. This review presents the results of a research series that identifies ectopic expressions and functions of ORs in non-chemosensory tissues to provide insight into future research directions.

• Molecules and Cells
• /
• v.43 no.4
• /
• pp.313-322
• /
• 2020

Eukaryotes transport biomolecules between intracellular organelles and between cells and the environment via vesicle trafficking. Soluble N-ethylmaleimide-sensitive factor attachment protein receptors (SNARE proteins) play pivotal roles in vesicle and membrane trafficking. These proteins are categorized as Qa, Qb, Qc, and R SNAREs and form a complex that induces vesicle fusion for targeting of vesicle cargos. As the core components of the SNARE complex, the SNAP25 Qbc SNAREs perform various functions related to cellular homeostasis. The Arabidopsis thaliana SNAP25 homolog AtSNAP33 interacts with Qa and R SNAREs and plays a key role in cytokinesis and in triggering innate immune responses. However, other Arabidopsis SNAP25 homologs, such as AtSNAP29 and AtSNAP30, are not well studied; this includes their localization, interactions, structures, and functions. Here, we discuss three biological functions of plant SNAP25 orthologs in the context of AtSNAP33 and highlight recent findings on SNAP25 orthologs in various plants. We propose future directions for determining the roles of the less well-characterized AtSNAP29 and AtSNAP30 proteins.

• Korean Journal of Food Science and Technology
• /
• v.44 no.6
• /
• pp.653-657
• /
• 2012

While it is known that sulfur containing amino acids (SCAA) are very important in regulating hepatocyte growth and preventing liver-diseases, the fundamental molecular mechanisms of how they exert their hepatoprotective functions are not well known. Since it is widely understood that the hepatic concentrations of S-adenosylmethionine (SAMe) in chronic liver disease patients are severely decreased, the pathophysiological importance of SAMe and its downstream antioxidant, glutathione should be discussed in order to see a big picture of relationship between SCAA and liver diseases. Chronic SAMe deficient mice have shown spontaneous hepatocellular carcinoma development due to impaired mitochondria functions with low levels of prohibitin1 protein, and through deficiency in many genes which are known to ameliorate genetic instability, such as APEX1 and DUSP1, the functions of which are recovered by SAMe treatment. In this review, current knowledge of the basic concepts of the mechanisms through which SCAAs protect the liver will be discussed in detail. Also, a possible tumor suppressor in livers, prohibitin1, and its functional relationship with SAMe will be discussed.

• Molecules and Cells
• /
• v.39 no.4
• /
• pp.358-366
• /
• 2016

The digestive system is gaining interest as a major regulator of various functions including immune defense, nutrient accumulation, and regulation of feeding behavior, aside from its conventional function as a digestive organ. The Drosophila midgut epithelium is completely renewed every 1-2 weeks due to differentiation of pluripotent intestinal stem cells in the midgut. Intestinal stem cells constantly divide and differentiate into enterocytes that secrete digestive enzymes and absorb nutrients, or enteroendocrine cells that secrete regulatory peptides. Regulatory peptides have important roles in development and metabolism, but study has mainly focused on expression and functions in the nervous system, and not much is known about the roles in endocrine functions of enteroendocrine cells. We systemically examined the expression of 45 regulatory peptide genes in the Drosophila midgut, and verified that at least 10 genes are expressed in the midgut enteroendocrine cells through RT-PCR, in situ hybridization, antisera, and 25 regulatory peptide-GAL transgenes. The Drosophila midgut is highly compartmentalized, and individual peptides in enteroendocrine cells were observed to express in specific regions of the midgut. We also confirmed that some peptides expressed in the same region of the midgut are expressed in mutually exclusive enteroendocrine cells. These results indicate that the midgut enteroendocrine cells are functionally differentiated into different subgroups. Through this study, we have established a basis to study regulatory peptide functions in enteroendocrine cells as well as the complex organization of enteroendocrine cells in the Drosophila midgut.