• BMB Reports
• /
• 제57권5호
• /
• pp.256-261
• /
• 2024

In the context of aging, the susceptibility to infectious diseases increases, leading to heightened morbidity and mortality. This phenomenon, termed immunosenescence, is characterized by dysregulation in the aging immune system, including abnormal alterations in lymphocyte composition, elevated basal inflammation, and the accumulation of senescent T cells. Such changes contribute to increased autoimmune diseases, enhanced infection severity, and reduced responsiveness to vaccines. Utilizing aging animal models becomes imperative for a comprehensive understanding of immunosenescence, given the complexity of aging as a physiological process in living organisms. Our investigation focuses on Cisd2, a causative gene for Wolfram syndrome, to elucidate on immunosenescence. Cisd2 knockout (KO) mice, serving as a model for premature aging, exhibit a shortened lifespan with early onset of aging-related features, such as decreased bone density, hair loss, depigmentation, and optic nerve degeneration. Intriguingly, we found that the Cisd2 KO mice present a higher number of neutrophils in the blood; however, isolated neutrophils from these mice display functional defects. Through mass spectrometry analysis, we identified an interaction between Cisd2 and Calnexin, a protein known for its role in protein quality control. Beyond this function, Calnexin also regulates calcium homeostasis through interaction with sarcoendoplasmic reticulum calcium transport ATPase (SERCA). Our study proposes that Cisd2 modulates calcium homeostasis via its interaction with Calnexin and SERCA, consequently influencing neutrophil functions.

• 한국독성학회:학술대회논문집
• /
• 한국독성학회 2003년도 춘계학술대회 논문집
• /
• pp.73-74
• /
• 2003

Familial form of Alzheimer's disease (FAD) is caused by mutations in presenilin-1 and presenilin-2 (PS2). PS1 and PS2 mutation are known to similar effects on the production of amyloid $\beta$ peptide (A$\beta$) and cause of cell death in the Alzheimer's brain. The importance of the alternation of calcium homeostasis in the neuronal cell death by PS1 mutation in a variety of experimental system has been demonstrated. (omitted)

• The Korean Journal of Physiology and Pharmacology
• /
• 제2권6호
• /
• pp.653-659
• /
• 1998

• 한국영양학회:학술대회논문집
• /
• 한국영양학회 1998년도 춘계학술대회 초록
• /
• pp.66-66
• /
• 1998

• 한국식품영양학회지
• /
• 제29권2호
• /
• pp.290-299
• /
• 2016

This study was conducted to determine the association between dietary calcium intake and biomarkers related to lipid and glucose metabolism and inflammation in Korean patients with type 2 diabetes. Seventy-five subjects (41 males, 34 females) were recruited from a group of patients who had visited the department of endocrine medicine. Data on anthropometric characteristics, clinical indices such as hemoglobin A1c and C-reactive protein (CRP), and dietary nutrient intakes were collected. Subjects were divided into three groups on the basis of their calcium intake [< EAR (below estimated average requirement), EAR-RNI (between EAR and recommended nutrient intake), > RNI (above RNI)]. Average calcium intake of < EAR, EAR-RNI, > RNI groups were $462.7{\pm}18.7$, $649.7{\pm}12.8$, and $895.7{\pm}21.7mg$, respectively. Energy intake was not different among groups but intakes of protein, total and saturated fatty acids were significantly higher in > RNI group than < EAR group. Analysis of covariance revealed that HDL cholesterol level was significantly higher in EAR-RNI group, as compared to < EAR group after adjustment with confounders such as age, sex, BMI and energy intake (p < 0.05). Levels of CRP and homeostasis model assessment 2-insulin resistance (HOMA2-IR) were significantly lower in EAR-RNI group. Total cholesterol level was higher in EAR-RNI and > RNI groups, although within the normal range. Our results suggest that dietary calcium intake may influence the levels of HDL-cholesterol, CRP and HOMA2-IR and subsequently, help management/treatment of type 2 diabetes patients.

• Toxicological Research
• /
• 제14권4호
• /
• pp.507-513
• /
• 1998

The purpose of this study was to clarify the effect of silica on cytosolic free calcium mobilization and cell injury in primary cultured rat hepatocytes. Cytosolic free calcium concentration ([Ca$^{2+}$]) was measured employing calcium sensitive fluorescent dye, Fura-2 / AM, and cell injury was evaluated by determination of cellular ATP contents. Silica increased [Ca$^{2+}$], in a concentration-dependent manner in hepatocytes (10$^{-5}$ ~10$^{-2}$ M). Silica caused a biphasic increase in [Ca$^{2+}$], which was composed of an initial rapid rise and following sustained phase. $Ca^{2+}$ removal from the medium resulted in abolishment of initial and sustained phase of silica (10$^{-2}$ M)-induced [Ca$^{2+}$], in hepatocytes. The pretreatment with nifedipine (1 $\mu$M) attenuated silica-induced [Ca$^{2+}$], increases. Silica decreased cellular ATP contents in a dose-dependent manner. This silica-induced cell injury was attenuated by the pretreatment with EGTA (100 $\mu$M) and nifedipine (1 $\mu$M). This study suggests that the elevation of [Ca$^{2+}$], caused by silica may be due mainly to influx through a plasma membrane $Ca^{2+}$ channel and hepatotoxicity by silica relate with alteration of calcium homeostasis.ium homeostasis.

• Journal of Microbiology and Biotechnology
• /
• 제31권6호
• /
• pp.765-774
• /
• 2021

Although research on the osteal signaling pathway has progressed, understanding of gut microbial-dependent signaling pathways for metabolic and immune bone homeostasis remains elusive. In recent years, the study of gut microbiota has shed light on our understanding of bone homeostasis. Here, we review microbiota-mediated gut-bone crosstalk via bone morphogenetic protein/SMADs, Wnt and OPG/receptor activator of nuclear factor-kappa B ligand signaling pathways in direct (translocation) and indirect (metabolite) manners. The mechanisms underlying gut microbiota involvement in these signaling pathways are relevant in immune responses, secretion of hormones, fate of osteoblasts and osteoclasts and absorption of calcium. Collectively, we propose a signaling network for maintaining a dynamic homeostasis between the skeletal system and the gut ecosystem. Additionally, the role of gut microbial improvement by dietary intervention in osteal signaling pathways has also been elucidated. This review provides unique resources from the gut microbial perspective for the discovery of new strategies for further improving treatment of bone diseases by increasing the abundance of targeted gut microbiota.

• Molecules and Cells
• /
• 제44권10호
• /
• pp.758-769
• /
• 2021

Calcium homeostasis modulator 1 (CALHM1) is a membrane protein with four transmembrane helices that form an octameric ion channel with voltage-dependent activation. There are four conserved cysteine (Cys) residues in the extracellular domain that form two intramolecular disulfide bonds. We investigated the roles of C42-C127 and C44-C161 in human CALHM1 channel biogenesis and the ionic current (I_CALHM1). Replacing Cys with Ser or Ala abolished the membrane trafficking as well as I_CALHM1. Immunoblotting analysis revealed dithiothreitol-sensitive multimeric CALHM1, which was markedly reduced in C44S and C161S, but preserved in C42S and C127S. The mixed expression of C42S and wild-type did not show a dominant-negative effect. While the heteromeric assembly of CALHM1 and CALHM3 formed active ion channels, the co-expression of C42S and CALHM3 did not produce functional channels. Despite the critical structural role of the extracellular cysteine residues, a treatment with the membrane-impermeable reducing agent tris(2-carboxyethyl) phosphine (TCEP, 2 mM) did not affect I_CALHM1 for up to 30 min. Interestingly, incubation with TCEP (2 mM) for 2-6 h reduced both I_CALHM1 and the surface expression of CALHM1 in a time-dependent manner. We propose that the intramolecular disulfide bonds are essential for folding, oligomerization, trafficking and maintenance of CALHM1 in the plasma membrane, but dispensable for the voltage-dependent activation once expressed on the plasma membrane.

• Journal of Nutrition and Health
• /
• 제30권4호
• /
• pp.394-405
• /
• 1997

Endogenous zinc is important for maintaining zinc homeostasis because the size of endogenous zinc pool is almost 3-4 times bigger than that of dietary zinc. The purpose of this study was to examine the phytate effect on the reabsorption of endogenous zinc and the additional Ca effect on the phytate effect. Rats were fed a casein-based diet with added sodium phytate containing either high(1.6%) or low(0.8%) Ca concentrations for 4 weeks to reduce the body zinc pool. After the depletion period, $^{65}$ Zn was given by intraperitoneal injection to label the endogenous zinc pool. Rats were then assigned into phytate or non-phytate group within the same Ca group. feces were collected for 2 weeks of the initial collection period and 1 week after dietary crossover. The ratios of excreted fecal $^{65}$ Zn radioactivity of phytate group non-phytate group were determined as a measure of the phytate effect on the endogenous zinc. Mean fecal $^{65}$ Zn radioactivity was higher in the phytate group than in the non-phytate group during the entire 3 weeks of the collection period in the low Ca group, and during the initial collection period in the high Ca group(p <0.0001). This study showed an adverse phytate effect on endogenous zinc at both high and low dietary Ca levels. Elevated dietary Ca levels showed a synergistic effect on the phytate effect on endogenous zinc(p <0.05). These results imply greater phytate effect on zinc homeostasis rather than on zinc bioavailability through complexing with the endogenous zinc which is larger portion than the dietary zinc on zinc homeostasis.

• Journal of Dairy Science and Biotechnology
• /
• 제22권2호
• /
• pp.143-150
• /
• 2004

The osteoporosis is a disease characterized by lower bone mineral content, deterioration of bone tissue and a reduction in the protein and mineral matrix of the bone. The bone becomes more porous leading to increased bone fragility and risk of fracture, particularly of the hip, spine and wrist. Osteoporosis can result in disfigurement, lowered self·esteem, reduction or loss of mobility, and decreased independence. Adequate calcium intake through milk and milk products in childhood and adolescence is a decisive marker for obtaining a maximum bone mass (peak adult bone mass) and f3r the prevention of osteoporosis. Calcium is one of the most critical nutrients associated with the osteoporosis. Dietary calcium is of great significance for healthy skeletal growth and development. The bone mineral content and bone mineral density of young adults is directly related to the calcium intake through milk and dairy products. Milk and milk products are the important sources of calcium as the richness and bioavailability of this nutrient is very high as compared to other food products. If enough calcium is not supplemented through diet, calcium from the bone will be depleted to maintain the blood plasma calcium level. The article focuses on the various issues related to osteoporosis manifestation and the role of dietary calcium especially calcium derived from dairy products.