Der moralisch gebietende Gott: Über den praktischen Gottesbegriff im ersten Konvolut Kants Nachlasswerks

조성엽 한국헤겔학회 2023 헤겔연구 Vol.- No.53

In dieser Untersuchung befasse ich mich mit Kants These in seinem Nachlasswerk, dass das Moralgesetz zugleich als das Gottesgebot zu betrachten ist, sowie deren Überzeugungskraft in Kants philosophischem System. Vom scholastischen Gottesbegriff ausgehend definiert Kant im ersten Konvolut seines Nachlasswerks den Gott als ein allmächtiges, allwissendes und allgütiges Wesen. Es ist allerdings alles andere als offensichtlich, wie sein spekulatives Konzept Gottes innerhalb seines philosophischen Systems harmonisch zu positionieren ist, ohne dabei einen Konflikt mit den Hauptthesen der kantischen Philosophie zu verursachen. Durch die Analyse von Kants Darlegungen sowie deren Vergleich mit seinen früheren Aussagen in der kritischen Werkperiode schlage ich jedoch die Interpretationsthese vor, seine These als eine Fortführung seiner Postulatenlehre zu lesen, im Gegensatz zur derzeit vorherrschenden Deutung, dass Kant in seinen späteren Jahren auf seinen moraltheologischen Gottesbegriff verzichtete.

Transglutaminase 2 inhibits apoptosis induced by calciumoverload through down-regulation of Bax

조성엽,김인규,Jin-Haeng Lee,Han-Dong Bae,정의만,Gi-Yong Jang,Chai-Wan Kim,Dong-Myung Shin,전주홍 생화학분자생물학회 2010 Experimental and molecular medicine Vol.42 No.9

An abrupt increase of intracellular Ca2+ is observed in cells under hypoxic or oxidatively stressed conditions. The dysregulated increase of cytosolic Ca2+ triggers apoptotic cell death through mitochondrial swelling and activation of Ca2+-dependent enzymes. Transglutaminase 2 (TG2) is a Ca2+-dependent enzyme that catalyzes transamidation reaction producing cross-linked and polyaminated proteins. TG2 activity is known to be involved in the apoptotic process. However, the pro-apoptotic role of TG2 is still controversial. In this study, we investigate the role of TG2 in apoptosis induced by Ca2+-overload. Overexpression of TG2 inhibited the A23187-induced apoptosis through suppression of caspase-3 and -9 activities, cytochrome c release into cytosol, and mitochondria membrane depolarization. Conversely, down-regulation of TG2caused the increases of cell death, caspase-3 activity and cytochrome c in cytosol in response to Ca2+-overload. Western blot analysis of Bcl-2 family proteins showed that TG2 reduced the expression level of Bax protein. Moreover, overexpression of Bax abrogated the anti-apoptotic effect of TG2, indicating that TG2-mediated suppression of Bax is responsible for inhibiting cell death under Ca2+-overloaded conditions. Our findings revealed a novel anti-apoptotic pathway involving TG2, and suggested the induction of TG2 as a novel strategy for promoting cell survival in diseases such as ischemia and neurodegeneration.

Patient-derived xenografts as compatible models for precision oncology

조성엽 한국실험동물학회 2020 Laboratory Animal Research Vol.36 No.2

Cancer is a very heterogeneous disease, displaying heterogeneity between patients (inter-tumoral heterogeneity) and heterogeneity within a patient (intra-tumoral heterogeneity). Precision oncology is a diagnostic and therapeutic approach for cancers based on the stratification of patients using genomic and molecular profiling of tumors. To develop diagnostic and therapeutic tools for the application of precision oncology, appropriate preclinical mouse models that reflect tumor heterogeneity are required. Patient-derived xenograft (PDX) models are generated by the engraftment of patient tumors into immunodeficient mice that retain several aspects of the patient’s tumor characteristics, including inter-tumoral heterogeneity and intra-tumoral heterogeneity. Therefore, PDX models can be applied in various developmental steps of cancer diagnostics and therapeutics, such as biomarker development, companion diagnostics, drug efficacy testing, overcoming drug resistance, and co-clinical trials. This review summarizes the diverse aspects of PDX models, addressing the factors considered for PDX generation, application of PDX models for cancer research, and future directions of PDX models.

A Detailed Analysis of Alcohol Pharmacokinetics in Healthy Korean Men

조성엽,한혜경,신광희,안형미,유경상,송병준,유성호 대한법의학회 2015 대한법의학회지 Vol.39 No.2

To determine blood alcohol concentration (BAC) by extrapolation, an understanding of basal pharmacokinetics is indispensable. Breath alcohol concentration (BrAC) has been used for the determination of body alcohol concentration replaced by BAC in Korea. Therefore, the determination of BAC/BrAC ratio is a key problem in alcohol pharmacokinetics. Among several factors, the ingested dose of alcohol and the allelic variation of mitochondrial aldehyde dehydrogenase 2 (ALDH2) are the most significant factors influencing the pharmacokinetic parameters, particularly in the absorption and elimination phases. This study shows a detailed pharmacokinetic analysis of BAC and BrAC associated with genetic polymorphism including ALDH2 in 42 healthy Korean men. The change in the alcohol dose ingested influenced the maximum concentration (Cmax), the time to reach Cmax (Tmax), the absorption rate constant (K01), the area under the concentration-time curve (AUClast), and the hourly elimination rate. The conversion of wild-type 487Glu (ALDH2*1) to 487Lys (ALDH2*2) in human ALDH2 resulted in changes in Cmax (ALDH2*1/*1, 0.03±0.01 g/dL [±standard deviation] vs. ALDH2*1/*2, 0.05±0.004 g/dL [P<0.01]), AUClast (ALDH2*1/*1, 4.48±2.19 g∙min/dL vs. ALDH2*1/*2, 7.52±1.26 g∙min/dL [P<0.05]), and the BAC elimination rate (ALDH2*1/*1, 0.05±0.02 g/L/hr vs. ALDH2*1/*2, 0.09±0.01 g/L/hr [P<0.05]). Moreover, the comparison of BAC and BrAC by Bland-Altman plot showed good agreement, suggesting that the measurement of BrAC can be a good alternative for the determination of BAC, particularly in the post-absorption phase. These results provide fundamental information about the pharmacokinetics of alcohol and the determination of BAC in forensics.

High prevalence of TP53 mutations is associated with poor survival and an EMT signature in gliosarcoma patients

조성엽,박창호,나득채,한지윤,이지은,박옥경,장정승,성창옥,문효은,김요나,김정훈,김종재,강신광,남도현,최정원,서연림,김동규,박성혜,윤혜원,윤규손,김종일,Charles Lee,백선하,박한수 생화학분자생물학회 2017 Experimental and molecular medicine Vol.49 No.-

Gliosarcoma (GS) is a rare variant (2%) of glioblastoma (GBM) that poses clinical genomic challenges because of its poor prognosis and limited genomic information. To gain a comprehensive view of the genomic alterations in GS and to understand the molecular etiology of GS, we applied whole-exome sequencing analyses for 28 GS cases (6 blood-matched fresh-frozen tissues for the discovery set, 22 formalin-fixed paraffin-embedded tissues for the validation set) and copy-number variation microarrays for 5 blood-matched fresh-frozen tissues. TP53 mutations were more prevalent in the GS cases (20/28, 70%) compared to the GBM cases (29/90, 32%), and the GS patients with TP53 mutations showed a significantly shorter survival (multivariate Cox analysis, hazard ratio=23.9, 95% confidence interval, 2.87–199.63, P=0.003). A pathway analysis showed recurrent alterations in MAPK signaling (EGFR, RASGRF2 and TP53), phosphatidylinositol/calcium signaling (CACNA1s, PLCs and ITPRs) and focal adhesion/tight junction (PTEN and PAK3) pathways. Genomic profiling of the matched recurrent GS cases detected the occurrence of TP53 mutations in two recurrent GS cases, which suggests that TP53 mutations play a role in treatment resistance. Functionally, we found that TP53 mutations are associated with the epithelial–mesenchymal transition (EMT) process of sarcomatous components of GS. We provide the first comprehensive genome-wide genetic alternation profiling of GS, which suggests novel prognostic subgroups in GS patients based on their TP53 mutation status and provides new insight in the pathogenesis and targeted treatment of GS.

바르트와 포이어바흐의 대결: 신은 진정 인간의 투사인가?

조성엽 한신대학교 신학사상연구소 2019 신학사상 Vol.0 No.186

In this paper, I review the confrontation between Karl Barth and Ludwig Feuerbach about Feuerbach’s theory of religious projection. Feuerbach insists that the concept of God necessarily presupposes a certain concept of humanity because God is always projected to be its supreme model. However, Barth indicates that Feuerbach deifies human beings while identifying them with God, which is unacceptable due to the absolute distinction between God and human being. Some researchers attempt to save Feuerbach from Barth’s criticism, supposing Barth commits a petitio principii to presuppose God’s existence to search for the foundation that will guarantee his knowledge of God. Those arguments also represent fundamental differences between Christian theology and philosophy which frustrate their attempts to communicate, in spite of their sincerity. In this paper, I attempt to uncover the real issue which neither Barth nor Feuerbach were aware of, and thereby seek possibilities to reconcile Barth and Feuerbach, and by extention theology and philosophy. 본 연구는 포이어바흐의 투사 이론에 관한 바르트와 포이어바흐의 대결을 고찰한다. 포이어바흐에 따르면 신은 언제나 인간성의 전범이자 투사로서만 인식된다. 따라서 신의 개념은 언제나 인간성에 대한 특정 개념을 전제한 다음에 성립한다. 그러나 바르트는 포이어바흐가 인간을 신과 동일시함으로써 인간을 신격화하며, 신과 인간 사이의 근본적 구별로 말미암아 이는 받아들일 수 없는 입장이라고 일축한다. 일련의 연구자들은 바르트의 비판으로부터 포이어바흐를 구출하고자 바르트가 신에 대한 인식을 보증하기 위한 근거로 신의 존재를 전제하는 선결문제 요구 의 오류를 범한다고 지적한다. 이는 기독교 신학과 철학 사이의 근본적 차이를 나타내는 지점이자 진지한 노력에도 불구하고 바르트와 포이어바흐의 대화가 가로막힌 원인이다. 본 연구는 결국 둘을 불일치로 귀결시킨 쟁점을 드러내고자 시도하며 이로써 바르트와 포이어바흐, 나아가 신학과 철학 사이 화해의 가능성을 다시금 모색한다.

자기살해와 채무위반 - 칸트 실천철학에서 완전한 의무의 위반 사례들에 대한 연구

조성엽 서울대학교 철학사상연구소 2022 철학사상 Vol.83 No.-

In this study, I analyse Kant’s arguments about immorality of suicide and default and suggest an alternative reading, in an effort to resolve the uncertanties in his arguments. In his Groundwork of Metaphysics of Morals and Critique of Practical Reason, Kant argues that the maxims that allows suicide and default cannot be accepted, because they may cause a practical paradox, when universalized. Dieter Scönecker criticises, however, that Kant’s arguments are based on dubious principles that cannot provide genuine standard of ethical judgment about maxims. But Kant hereby does not intend to prove the moral inadequacy of those maxims, but to illustrate his formula of the categorical imperative, borrowing the form of practical paradox. 본 연구의 목적은 자기살해와 채무위반을 완전한 의무의 위반 사례들로 꼽는 칸트의 논증을 검토하고, 그 문제적 성격을 해소하기 위한 새로운 독해 방법을 제시하는 것이다. 정초 와 실천이성비판 에서 칸트는 해당 행위들을 명령하는 준칙이 보편화되었을 때 실천적 모순을 초래하기 때문에 이들 역시 윤리적 준칙이 아니라고 주장한다. 이에 대해 디히터 쉐네커는 실천적 모순의 초래 여부가 윤리적 판단의 기준으로 인용될 수 없다고 비판한다. 그러나 칸트의 논변은 자기살해 및 채무위반 준칙의 부적합성을 보이기 위해서가 아니라, 그가 앞서 입안한 윤리적 정언명령의 정식을 입증하기 위해 도입된 것이다.

Doxorubicin Induces the Persistent Activation of Intracellular Transglutaminase 2 That Protects from Cell Death

조성엽,김인규,정의만,Jin-Haeng Lee,Hyo-Jun Kim,Jisun Lim,Chai-Wan Kim,Dong-Myung Shin,전주홍,최경호 한국분자세포생물학회 2012 Molecules and cells Vol.33 No.3

The activation of transglutaminase 2 (TG2), an enzyme that catalyzes post-translational modifications of proteins, has been implicated in apoptosis, cell adhesion and inflammatory responses. We previously reported that intracellular TG2 is activated under oxidative stress conditions, such as ultraviolet irradiation, ischemia-reperfusion, and hypo-xia. In this study, we examined the effect of genotoxic stress on the intracellular activity of TG2 using doxorubicin which generates reactive oxygen species that lead to double-strand breakage of DNA. We demonstrated that doxorubicin elicits the persistent activation of TG2. Doxo-rubicin-induced TG2 activity was suppressed by treatment with caffeine at the early phase, N-acetylcysteine at the mid-phase, and EGTA at the late phase. However, treatment with a blocking antibody against TGF or toll-like receptor 2 showed no effect on TG2 activity, indicating that at least three different signaling pathways may be involved in the process of TG2 activation. In addition, using MEF cells defective for TG2 and cells overexpressing an active-site mutant of TG2, we revealed that doxorubicin-induced cell death is inversely correlated with TG2 activity. Our findings indicate that the persistent activation of TG2 by doxorubicin contributes to cell survival, suggesting that the mechanism-based inhibition of TG2 may be a novel strategy to prevent drug-resistance in doxorubicin treat-ment.

왜 윤리적인 사람이 행복해야만 하는가? -칸트 철학의 ‘행복할 품격’ 개념 검토-

조성엽(Jo, Sung-Yeop) 서울대학교 철학사상연구소 2019 철학사상 Vol.72 No.-

본 연구의 목적은 칸트 철학에서 ‘품격’ 개념의 역할을 명확히 규정하며, 이로 말미암아 발생하는 칸트 윤리학과 최고선 이론 사이의 비일관성 문제에 대해 가능한 해결책을 발견하는 것이다. 칸트는 윤리적 실천을 ‘행복할 품격’으로 규정한다. 즉, 이는 ‘도덕적으로 행위한 사람이 다시금 행복해야 한다’는 당위성인데, 칸트는 이에 대한 직관적 확신을 가진 것으로 보인다. 때문에 이에 대해 『실천이성비판』과 『판단력비판』에서는 이를 직접 논증하지 않는다. 반면 『순수이성비판』에서는 도덕적 책무의 개념으로부터 이를 정당화한다. 여기에서 칸트는 인간이 그의 도덕적 행위에 비례하여 행복해야만 하는 이유를 그러한 행복에의 희망이 인간을 도덕적 행위로 인도한다는 점에서 찾는다. 아울러 『실천이성비판』 제2부의 스토아 철학 비판을 통해서도 같은 입장을 확인할 수 있다. 다만 문제는 이러한 윤리적 실천의 토대로서 행복의 개념이 칸트 윤리학의 형식주의와 양립가능한지의 여부이다. 칸트 윤리학과 최고선 이론 사이의 긴장은 여러 선행 연구를 통해서 이미 주지된 바이다. 본 연구는 칸트 자신이 시도한 윤리적 의지의 ‘규정 근거’와 ‘전 대상’의 구별로부터 둘의 양립가능성을 발견한다. 행복이 의지의 규정 근거로 활용되는 경우 이는 분명 윤리성의 결격사유이다. 그러나 이는 윤리적 의지가 지향하는 대상에 행복이 포함될 가능성을 배제하지 않는다. In the research herein, I attempt to disentangle the concept of ‘worthiness to be happy’ and its role in Kantian philosophy. I also extrapolate a possible solution to the seeming inconsistency between Kantian ethics and his theory of the highest good, an issue that can be properly addressed through the ‘worthiness’ concept. Kant defines moral conduct as worthiness to be happy. This implies that the person who behaves morally also ought to be happy. Kant appears to argue for this intuitively, and does not provide further justifications in his second and third Critiques. However, in the first Critique, he seems to derive such a necessity from the concept of moral responsibility. Here, Kant maintains that one should be happy in a proportion to his moral conduct because the hope for such happiness actually helps human beings to behave morally. We find that this stance continues in the second Critique, especially in Kant’s refutation to the Stoics. The problem lies in the seeming incompatibility between Kant’s concept of happiness as a foundation of moral practice and his ethical formalism. The tension between Kantian ethics and his theory of the highest good has long been noted by many preceding research studies. I herein make an attempt at a possible solution emerging from Kant’s distinction between the determining ground and the whole object of moral will. Obviously, the moral conduct becomes disqualified if the will is driven by expectation for happiness. However, this does not necessarily exclude happiness from being proper objects of moral will.

칸트 역사철학에서 ‘자연의 계획’ 개념 검토

조성엽(Jo Sung-Yeop) 서울대학교 철학사상연구소 2018 철학사상 Vol.69 No.-

본 연구는 『세계 시민적 관점에서 본 보편사의 이념』에서 사용된 ‘자연의 계획’ 개념의 지지 근거를 모색한다. 『보편사』에서 이 개념은 역사의 진보에 대한 희망을 뒷받침하는 논거로 사용된다. 다만 이 개념 자체에 대해서도 문제제기가 가능한데, 이에 대해 가능한 응답을 『판단력비판』의 제2부로부터 발견할 수 있다. ‘목적론적 판단력 비판’에서 칸트는 목적 인과의 사용 원리를 밝히며 이에 의해 자연을 합목적적 전체로 파악한다. 자연은 예지적 인간의 현존이라는 궁극 목적 아래에서 하나의 체계로 구성된다. 자연은 인간의 문화적 현존이 가능한 토대를 제공함으로써 궁극 목적에 기여한다. 역사는 자연의 토대로부터 인간이 문화를 계발하며, 이에 의해 자기의 자연적 경향성을 교정하고 도덕적 존재로의 도야를 이루는 과정이다. 따라서 역사는 합목적적 자연이 자기의 궁극 목적을 실현하는 과정의 일부이다. 이는 목적 인과에 의한 추론을 자연 및 역사에 대한 직관에 적용함으로써 지지된다. In this study, I search for the basis of the concept of the ‘plan of nature’ used in Idea of a Universal History with a Cosmopolitan Purpose. Herein, ‘plan of nature’ provides the basis for hope for the progress of history. However, the concept itself is so problematic, that further justification needs to be provided. To this purpose, I involve the second chapter of Critique of Judgment. Through critique of teleological judgment, Kant develops the principle of teleological causality, and thereby regards nature as a purposive whole. Nature constitutes a system under the ultimate purpose of intelligible humans, which Nature contributes to by providing the foundation of culture. History is the process through which humans develop their own culture from the natural foundation, and then educate themselves for morality while restraining their natural inclination. Thereby history becomes the part of the process through which purposive nature fulfills its ultimate purpose. It is supported by the application of purposive causality to the instinctive knowledge [Anschauung] upon nature and history.