• BMB Reports
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• 제57권3호
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• pp.155-160
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• 2024

Lung cancer carries one of the highest mortality rates among all cancers. It is often diagnosed at more advanced stages with limited treatment options compared to other malignancies. This study focuses on calnexin as a potential biomarker for diagnosis and treatment of lung cancer. Calnexin, a molecular chaperone integral to N-linked glycoprotein synthesis, has shown some associations with cancer. However, targeted therapeutic or diagnostic methods using calnexin have been proposed. Through 1D-LCMSMS, we identified calnexin as a biomarker for lung cancer and substantiated its expression in human lung cancer cell membranes using Western blotting, flow cytometry, and immunocytochemistry. Anti-calnexin antibodies exhibited complement-dependent cytotoxicity to lung cancer cell lines, resulting in a notable reduction in tumor growth in a subcutaneous xenograft model. Additionally, we verified the feasibility of labeling tumors through in vivo imaging using antibodies against calnexin. Furthermore, exosomal detection of calnexin suggested the potential utility of liquid biopsy for diagnostic purposes. In conclusion, this study establishes calnexin as a promising target for antibody-based lung cancer diagnosis and therapy, unlocking novel avenues for early detection and treatment.

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

• BMB Reports
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• 제32권3호
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• pp.311-316
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• 1999

Studies in adipocytes indicate that secretion of active lipoprotein lipase (LPL) was strictly regulated by a quality control system in the endoplasmic reticulum (ER). However, there has been no report about the ER chaperones participating in the folding and assembly of LPL. Many chaperones are known to bind unfolded proteins and dissociate from them through the ATP-hydrolyzing reaction. In this study, putative ER chaperones for LPL were determined by affinity chromatography using denatured LPL as an affinity ligand and elution with ATP. BiP, grp94, calreticulin, and another 50 kDa K-D-E-L protein in the ER of rat adipose tissue were bound to denatured LPL and eluted by ATP. Calnexin was bound to denatured LPL; however, it was not eluted by ATP but by acetic acid. These results indicate that, at least, BiP, grp94, calreticulin, calnexin, and the unidentified 50 kDa protein might act as putative chaperones for the proper folding and assembly of LPL in ER.

• 생명과학회지
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• 제22권2호
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• pp.281-284
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• 2012

갑상선 배양세포(FRTL5)에서 ER stress에 의해서 ER chaperone (Bip, ERp29, Calnexin and PDI), ER stress sensor (PERK, ATF6 and Ire1)와 cAMP phosphodiesterase 7A1 (cAMP PDE7A1) 유전자발현이 증가하는 것을 알았다. 세포배양배지에서 A23187을 제거하면 cAMP PDE7A1 유전자발현이 회복되지만, thapsigagin의 경우는 회복되지 않았다. 그리고 A23187과 TSH를 함께 처리한 경우는 아주 강하게 cAMP PDE7A1 유전자의 발현이 억제되었다. 이 같은 결과는 ER stress에 의해서 cAMP PDE7A1 유전자발현이 상승 발현된다는 첫 보고이다.

• 대한의생명과학회지
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• 제14권1호
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• pp.59-62
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• 2008

This experiment was performed to study the effect of TSH (thyroid-stimulating hormone) on the expression of endoplasmic reticulum (ER) chaperones in the rat thyrocytes FRTL-5 cells. Although the expressions of ER membrane kinases (ATF6, IRE1 and PERK) were specially enhanced under absence of TSH, no remarkable up- or down regulations of ER chaperones (BiP, CHOP and Calnexin) were detected by TSH. We firstly report here that TSH by dose up-regulated expression of ER membrane kinases in FRTL-5 culture thyrocytes.

• Animal cells and systems
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• 제7권3호
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• pp.271-277
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• 2003

Regulation of endoplasmic reticulum(ER) chaperone, ERp29, in traumatized rat spinal cord was investigated. Compared to the control, ERp29 expression was down-regulated at the lesion site 1 d after spinal cord injury. However, ERp29 expression gradually increased from 3 d after the injury and peaked remarkably after 7 d. Two ER chaperones (GRP94 and BiP) showed constantly strong expression levels 1 d after spinal cord injury while the expression levels of the other two (calnexin and PDI) were unchanged. In the case of ERp72, its expression level was increased 1 d after the injury and gradually decreased thereafter. This study suggests that ERp29 expression in the spinal cord after traumatic injury might be associated with the posttraumatic neural survival, playing a role as a molecular chaperone.

• 약학회지
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• 제50권4호
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• pp.263-267
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• 2006

CD1d is an unique antigen presenting molecule which provides antigenic repertoires to NKT cells. To examine molecules required for CD1d antigen presentation, we determined an interaction between CD1d and several endoplasmic reticulum (ER) resident molecular chaperones by co-immunoprecipitation. Results indicated that calnexin and calreticulin seem to be bound to mouse CD1d, but TAP and tapasin do not bind. Further, we screened an yeat two hybrid system to identify proteins that help mouse CD1d transportation in the cytosol. We found that two proteins, heat shock protein a sub-unit $(Hsp90{\alpha})$ and protein kinase C and casein kinase substrate in neurons 3 (PACSIN-3), interact with CD1d. Future study will be focus on the role of these molecules during the CD1d antigen presentation.

• 생명과학회지
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• 제20권12호
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• pp.1820-1828
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• 2010

PC12 세포에서 $CoCl_2$에 의한 hypoxia 유도는 HIF1 alpha의 상승 발현으로 확인하였다. 이때 apoptosis의 유도는 genomic DNA의 fragmentation과 apoptotic body는 Hoechst 염색으로 확인되었고, ER luminal chaperone의 발현 및 ER stress signal에 관여하는 ER membrane kinase인 IRE1, PERK, ATF6의 발현도 확인되었다. 이들이 apoptosis로 연결되는 고리 역할을 하는 IRE1-XBP1 mRNA splicing, PERK-eIF2 alpha, ATF6 protein cleavage도 반응하는 것으로 확인되었다. 위의 결과는 신경세포의 hypoxia상태는 ER stress signal pathway를 거쳐서 apoptosis가 된다는 것을 증명한 것으로 신경세포의 hypoxia치료를 위한 기초 자료가 될 것으로 생각한다.