Cell Death Discovery最新文献_第2页

The mechanisms behind heatstroke-induced intestinal damage. 中暑诱发肠道损伤的机制。

IF 6.1 2区生物学

Cell Death Discovery Pub Date : 2024-10-28 DOI: 10.1038/s41420-024-02210-0

Minshu Sun, Qin Li, Zhimin Zou, Jian Liu, Zhengtao Gu, Li Li

{"title":"The mechanisms behind heatstroke-induced intestinal damage.","authors":"Minshu Sun, Qin Li, Zhimin Zou, Jian Liu, Zhengtao Gu, Li Li","doi":"10.1038/s41420-024-02210-0","DOIUrl":"10.1038/s41420-024-02210-0","url":null,"abstract":"With the frequent occurrence of heatwaves, heatstroke (HS) is expected to become one of the main causes of global death. Being a multi-organized disease, HS can result in circulatory disturbance and systemic inflammatory response, with the gastrointestinal tract being one of the primary organs affected. Intestinal damage plays an initiating and promoting role in HS. Multiple pathways result in damage to the integrity of the intestinal epithelial barrier due to heat stress and hypoxia brought on by blood distribution. This usually leads to intestinal leakage as well as the infiltration and metastasis of toxins and pathogenic bacteria in the intestinal cavity, which will eventually cause inflammation in the whole body. A large number of studies have shown that intestinal damage after HS involves the body's stress response, disruption of oxidative balance, disorder of tight junction proteins, massive cell death, and microbial imbalance. Based on these damage mechanisms, protecting the intestinal barrier and regulating the body's inflammatory and immune responses are effective treatment strategies. To better understand the pathophysiology of this complex process, this review aims to outline the potential processes and possible therapeutic strategies for intestinal damage after HS in recent years.","PeriodicalId":9735,"journal":{"name":"Cell Death Discovery","volume":null,"pages":null},"PeriodicalIF":6.1,"publicationDate":"2024-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11519599/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142521145","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

CDK4/6 inhibition initiates cell cycle arrest by nuclear translocation of RB and induces a multistep molecular response. CDK4/6 抑制通过 RB 的核转位启动细胞周期停滞，并诱发多步分子反应。

IF 6.1 2区生物学

Cell Death Discovery Pub Date : 2024-10-26 DOI: 10.1038/s41420-024-02218-6

Ting Hong, Anna C Hogger, Dongbiao Wang, Qi Pan, Julie Gansel, Thomas Engleitner, Rupert Öllinger, Jürgen E Gschwend, Roland Rad, Roman Nawroth

{"title":"CDK4/6 inhibition initiates cell cycle arrest by nuclear translocation of RB and induces a multistep molecular response.","authors":"Ting Hong, Anna C Hogger, Dongbiao Wang, Qi Pan, Julie Gansel, Thomas Engleitner, Rupert Öllinger, Jürgen E Gschwend, Roland Rad, Roman Nawroth","doi":"10.1038/s41420-024-02218-6","DOIUrl":"10.1038/s41420-024-02218-6","url":null,"abstract":"CDK4/6 inhibitors are standard of care in the treatment of metastatic breast cancer. Treatment regimen consists of a combination with endocrine therapy, since their therapeutic efficacy as monotherapy in most clinical trials was rather limited. Thus, understanding the molecular mechanisms that underlie response to therapy might allow for the development of an improved therapy design. We analyzed the response to the CDK4/6 inhibitor palbociclib in bladder cancer cells over a 48-hour time course using RNA sequencing and identified a multi-step mechanism of response. We next translated these results to the molecular mechanism in bladder cancer cells upon PD treatment. The initial step is characterized by translocation of the RB protein into the nucleus by activation of importin α/β, a mechanism that requires the NLS sequence. In parallel, RB is proteolyzed in the cytoplasm, a process regulated by gankyrin and the SCF complex. Only hypophosphorylated RB accumulates in the nucleus, which is an essential step for an efficient therapy response by initiating G1 arrest. This might explain the poor response in RB negative or mutated patients. At later stages during therapy, increased expression of the MiT/TFE protein family leads to lysosomal biogenesis which is essential to maintain this response. Lastly, cancer cells either undergo senescence and apoptosis or develop mechanisms of resistance following CDK4/6 inhibition.","PeriodicalId":9735,"journal":{"name":"Cell Death Discovery","volume":null,"pages":null},"PeriodicalIF":6.1,"publicationDate":"2024-10-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11513128/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142495898","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The oncogenic axis YAP/MYC/EZH2 impairs PTEN tumor suppression activity enhancing lung tumorigenicity. 致癌轴YAP/MYC/EZH2损害了PTEN的肿瘤抑制活性，从而增强了肺癌的致病性。

IF 6.1 2区生物学

Cell Death Discovery Pub Date : 2024-10-25 DOI: 10.1038/s41420-024-02216-8

Federica Lo Sardo, Chiara Turco, Beatrice Messina, Andrea Sacconi, Francesca Romana Auciello, Claudio Pulito, Sabrina Strano, Sima Lev, Giovanni Blandino

{"title":"The oncogenic axis YAP/MYC/EZH2 impairs PTEN tumor suppression activity enhancing lung tumorigenicity.","authors":"Federica Lo Sardo, Chiara Turco, Beatrice Messina, Andrea Sacconi, Francesca Romana Auciello, Claudio Pulito, Sabrina Strano, Sima Lev, Giovanni Blandino","doi":"10.1038/s41420-024-02216-8","DOIUrl":"https://doi.org/10.1038/s41420-024-02216-8","url":null,"abstract":"The tumor suppressor PTEN (phosphatase and tensin homolog deleted in chromosome 10) is genetically deleted or downregulated in many cancer types. Loss of PTEN protein expression is frequently found in lung cancer while genetic alterations are less abundant. PTEN expression is regulated at multiple genetic and epigenetic levels and even partial reduction of its expression increases cancer occurrence. We show that YAP and TAZ cooperate with EZH2, and MYC to transcriptionally repress onco-suppressor genes, including PTEN, in non-small cell lung cancer (NSCLC) cells. YAP/TAZ-EZH2-MYC transcriptional regulators form a nuclear complex that represses PTEN transcription, while their combinatorial targeting restores PTEN expression, attenuates NSCLC cell growth, and prevents compensatory responses induced by single treatments. Datasets analysis of NSCLC patients revealed that PTEN expression is negatively correlated to YAP/TAZ, EZH2 and MYC and that low expression of PTEN is predictive of poor prognosis, especially at earlier stages of the disease. These findings highlight the repressive role of the YAP/TAZ-EZH2-MYC axis on tumor-suppressor genes and offer a potential therapeutic strategy for lung cancer patients with low PTEN levels.","PeriodicalId":9735,"journal":{"name":"Cell Death Discovery","volume":null,"pages":null},"PeriodicalIF":6.1,"publicationDate":"2024-10-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11511861/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142495902","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Deciphering the nexus between long non-coding RNAs and endoplasmic reticulum stress in hepatocellular carcinoma: biomarker discovery and therapeutic horizons. 解密肝细胞癌中长非编码 RNA 与内质网应激之间的关系：生物标记物的发现与治疗前景。

IF 6.1 2区生物学

Cell Death Discovery Pub Date : 2024-10-24 DOI: 10.1038/s41420-024-02200-2

Himanshi Goyal, Sachin Parwani, Jyotdeep Kaur

{"title":"Deciphering the nexus between long non-coding RNAs and endoplasmic reticulum stress in hepatocellular carcinoma: biomarker discovery and therapeutic horizons.","authors":"Himanshi Goyal, Sachin Parwani, Jyotdeep Kaur","doi":"10.1038/s41420-024-02200-2","DOIUrl":"https://doi.org/10.1038/s41420-024-02200-2","url":null,"abstract":"Hepatocellular carcinoma (HCC) remains a significant global health challenge with few effective treatment options. The dysregulation of endoplasmic reticulum (ER) stress responses has emerged as a pivotal factor in HCC progression and therapy resistance. Long non-coding RNAs (lncRNAs) play a crucial role as key epigenetic modifiers in this process. Recent research has explored how lncRNAs influence ER stress which in turn affects lncRNAs activity in HCC. We systematically analyze the current literature to highlight the regulatory roles of lncRNAs in modulating ER stress and vice versa in HCC. Our scrutinization highlights how dysregulated lncRNAs contribute to various facets of HCC, including apoptosis resistance, enhanced proliferation, invasion, and metastasis, all driven by ER stress. Moreover, we delve into the emerging paradigm of the lncRNA-miRNA-mRNA axis, elucidating it as the promising avenue for developing novel biomarkers and paving the way for more personalized treatment options in HCC. Nevertheless, we acknowledge the challenges and future directions in translating these insights into clinical practice. In conclusion, our review provides insights into the complex regulatory mechanisms governing ER stress modulation by lncRNAs in HCC.","PeriodicalId":9735,"journal":{"name":"Cell Death Discovery","volume":null,"pages":null},"PeriodicalIF":6.1,"publicationDate":"2024-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11502918/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142495899","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Author Correction: Human adipose tissue-derived mesenchymal stem cells and their extracellular vesicles modulate lipopolysaccharide activated human microglia. 作者更正：人脂肪组织间充质干细胞及其细胞外囊泡可调节脂多糖激活的人小胶质细胞。

IF 6.1 2区生物学

Cell Death Discovery Pub Date : 2024-10-23 DOI: 10.1038/s41420-024-02209-7

Marta Garcia-Contreras, Avnesh S Thakor

引用次数: 0

Long non-coding RNA-encoded micropeptides: functions, mechanisms and implications. 长非编码 RNA 编码的微肽：功能、机制和影响。

IF 6.1 2区生物学

Cell Death Discovery Pub Date : 2024-10-23 DOI: 10.1038/s41420-024-02175-0

Yinan Xiao, Yaru Ren, Wenteng Hu, Athanasios R Paliouras, Wenyang Zhang, Linghui Zhong, Kaixin Yang, Li Su, Peng Wang, Yonghong Li, Minjie Ma, Lei Shi

{"title":"Long non-coding RNA-encoded micropeptides: functions, mechanisms and implications.","authors":"Yinan Xiao, Yaru Ren, Wenteng Hu, Athanasios R Paliouras, Wenyang Zhang, Linghui Zhong, Kaixin Yang, Li Su, Peng Wang, Yonghong Li, Minjie Ma, Lei Shi","doi":"10.1038/s41420-024-02175-0","DOIUrl":"https://doi.org/10.1038/s41420-024-02175-0","url":null,"abstract":"Long non-coding RNAs (lncRNAs) are typically described as RNA transcripts exceeding 200 nucleotides in length, which do not code for proteins. Recent advancements in technology, including ribosome RNA sequencing and ribosome nascent-chain complex sequencing, have demonstrated that many lncRNAs retain small open reading frames and can potentially encode micropeptides. Emerging studies have revealed that these micropeptides, rather than lncRNAs themselves, are responsible for vital functions, including but not limited to regulating homeostasis, managing inflammation and the immune system, moderating metabolism, and influencing tumor progression. In this review, we initially outline the rapidly advancing computational analytical methods and public tools to predict and validate the potential encoding of lncRNAs. We then focus on the diverse functions of micropeptides and their underlying mechanisms in the pathogenesis of disease. This review aims to elucidate the functions of lncRNA-encoded micropeptides and explore their potential applications as therapeutic targets in cancer.","PeriodicalId":9735,"journal":{"name":"Cell Death Discovery","volume":null,"pages":null},"PeriodicalIF":6.1,"publicationDate":"2024-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11499885/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142495900","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

C/EBPα-mediated ACSL4-dependent ferroptosis exacerbates tubular injury in diabetic kidney disease. C/EBPα介导的 ACSL4 依赖性铁蛋白沉积会加剧糖尿病肾病的肾小管损伤。

IF 6.1 2区生物学

Cell Death Discovery Pub Date : 2024-10-23 DOI: 10.1038/s41420-024-02179-w

Ziru Xia, Zhaonan Wei, Xin Li, Yunzi Liu, Xiangchen Gu, Jianhua Tong, Siyi Huang, Xiaoyue Zhang, Weiming Wang

{"title":"C/EBPα-mediated ACSL4-dependent ferroptosis exacerbates tubular injury in diabetic kidney disease.","authors":"Ziru Xia, Zhaonan Wei, Xin Li, Yunzi Liu, Xiangchen Gu, Jianhua Tong, Siyi Huang, Xiaoyue Zhang, Weiming Wang","doi":"10.1038/s41420-024-02179-w","DOIUrl":"https://doi.org/10.1038/s41420-024-02179-w","url":null,"abstract":"Diabetic kidney disease (DKD) is a prevalent and debilitating complication of diabetes characterized by progressive renal function decline and a lack of effective treatment options. Here, we investigated the role of the transcription factor CCAAT/enhancer binding protein alpha (C/EBPα) in DKD pathogenesis. Analysis of renal biopsy samples revealed increased C/EBPα expression in patients with DKD. Using RNA sequencing and proteomics, we explored the mechanisms through which the C/EBPα contributes to DKD. Our findings demonstrated that C/EBPα exacerbated tubular injury by promoting acyl-CoA synthetase long-chain family member 4 (ACSL4)-dependent ferroptosis. We identified that C/EBPα upregulated ACSL4 expression by binding to its transcription regulatory sequence (TRS), leading to elevated lipid peroxidation and ferroptosis. Furthermore, inhibition or genetic ablation of C/EBPα attenuated ferroptosis and mitigated tubular injury in DKD. These results highlighted the C/EBPα-ACSL4-ferroptosis pathway as a promising therapeutic target for DKD treatment.","PeriodicalId":9735,"journal":{"name":"Cell Death Discovery","volume":null,"pages":null},"PeriodicalIF":6.1,"publicationDate":"2024-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11499655/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142495897","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Mutation of the SUMOylation site of Aurora-B disrupts spindle formation and chromosome alignment in oocytes. Aurora-B 的 SUMOylation 位点突变会破坏卵母细胞中纺锤体的形成和染色体的排列。

IF 6.1 2区生物学

Cell Death Discovery Pub Date : 2024-10-22 DOI: 10.1038/s41420-024-02217-7

Shan-Shan Chen, Li Li, Bo Yao, Jia-Lun Guo, Ping-Shuang Lu, Hao-Lin Zhang, Kun-Huan Zhang, Yuan-Jing Zou, Nan-Jian Luo, Shao-Chen Sun, Lin-Lin Hu, Yan-Ping Ren

{"title":"Mutation of the SUMOylation site of Aurora-B disrupts spindle formation and chromosome alignment in oocytes.","authors":"Shan-Shan Chen, Li Li, Bo Yao, Jia-Lun Guo, Ping-Shuang Lu, Hao-Lin Zhang, Kun-Huan Zhang, Yuan-Jing Zou, Nan-Jian Luo, Shao-Chen Sun, Lin-Lin Hu, Yan-Ping Ren","doi":"10.1038/s41420-024-02217-7","DOIUrl":"https://doi.org/10.1038/s41420-024-02217-7","url":null,"abstract":"Aurora-B is a kinase that regulates spindle assembly and kinetochore-microtubule (KT-MT) attachment during mitosis and meiosis. SUMOylation is involved in the oocyte meiosis regulation through promoting spindle assembly and chromosome segregation, but its substrates to support this function is still unknown. It is reported that Aurora-B is SUMOylated in somatic cells, and SUMOylated Aurora-B contributes the process of mitosis. However, whether Aurora-B is SUMOylated in oocytes and how SUMOylation of Aurora-B impacts its function in oocyte meiosis remain poorly understood. In this study, we report that Aurora-B is modified by SUMOylation in mouse oocytes. The results show that Aurora-B colocalized and interacted with SUMO-2/3 in mouse oocytes, confirming that Aurora-B is modified by SUMO-2/3 in this system. Compared with that in young mice, the protein expression of SUMO-2/3 decreased in the oocytes of aged mice, indicating that SUMOylation might be related to mouse aging. Overexpression of Aurora-B SUMOylation site mutants, Aurora-BK207R and Aurora-BK292R, inhibited Aurora-B recruitment and first polar body extrusion, disrupting localization of gamma tubulin, spindle formation and chromosome alignment in oocytes. The results show that it was related to decreased recruitment of p-HDAC6 which induces the high stability of whole spindle microtubules including the microtubules of both correct and wrong KT-MT attachments though increased acetylation of microtubules. Therefore, our results corroborate the notion that Aurora-B activity is regulated by SUMO-2/3 in oocytes, and that SUMOylated Aurora B plays an important role in spindle formation and chromosome alignment.","PeriodicalId":9735,"journal":{"name":"Cell Death Discovery","volume":null,"pages":null},"PeriodicalIF":6.1,"publicationDate":"2024-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11496499/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142495901","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Upregulation of cholinergic modulators Lypd6 and Lypd6b associated with autism drives anxiety and cognitive decline. 与自闭症相关的胆碱能调节剂 Lypd6 和 Lypd6b 的上调会导致焦虑和认知能力下降。

IF 6.1 2区生物学

Cell Death Discovery Pub Date : 2024-10-21 DOI: 10.1038/s41420-024-02211-z

Aizek B Isaev, Maxim L Bychkov, Dmitrii S Kulbatskii, Alexander A Andreev-Andrievskiy, Mikhail A Mashkin, Mikhail A Shulepko, Olga V Shlepova, Eugene V Loktyushov, Alexander V Latanov, Mikhail P Kirpichnikov, Ekaterina N Lyukmanova

{"title":"Upregulation of cholinergic modulators Lypd6 and Lypd6b associated with autism drives anxiety and cognitive decline.","authors":"Aizek B Isaev, Maxim L Bychkov, Dmitrii S Kulbatskii, Alexander A Andreev-Andrievskiy, Mikhail A Mashkin, Mikhail A Shulepko, Olga V Shlepova, Eugene V Loktyushov, Alexander V Latanov, Mikhail P Kirpichnikov, Ekaterina N Lyukmanova","doi":"10.1038/s41420-024-02211-z","DOIUrl":"10.1038/s41420-024-02211-z","url":null,"abstract":"Intellectual disability and autistic features are associated with chromosome region 2q23.q23.2 duplication carrying LYPD6 and LYPD6B genes. Here, we analyzed LYPD6 and LYPD6B expression in patients with different neuropsychiatric disorders. Increased LYPD6 and LYPD6B expression was revealed in autism and other disorders. To study possible consequences of Lypd6 and Lypd6b overexpression in the brain, we used a mouse model with intracerebroventricular delivery of recombinant analogs of these proteins. A two-week infusion evoked significant memory impairment and acute stress. Both modulators downregulated hippocampal and amygdala dendritic spine density. No changes in synaptic plasticity were observed. Intracerebroventricular administration by both proteins downregulated hippocampal expression of Lypd6, Lypd6b, and α7 nicotinic acetylcholine receptor (nAChR). Similar to Lypd6, Lypd6b targeted different nAChR subtypes in the brain with preferential inhibition of α7- and α4β2-nAChRs. Thus, increased Lypd6 and Lypd6b level in the brain are linked to cholinergic system depression, neuronal atrophy, memory decline, and anxiety.","PeriodicalId":9735,"journal":{"name":"Cell Death Discovery","volume":null,"pages":null},"PeriodicalIF":6.1,"publicationDate":"2024-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11494011/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142485660","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Sleep restriction exacerbates cardiac dysfunction in diabetic mice by causing cardiomyocyte death and fibrosis through mitochondrial damage. 睡眠限制通过线粒体损伤导致心肌细胞死亡和纤维化，从而加剧糖尿病小鼠的心脏功能障碍。

IF 6.1 2区生物学

Cell Death Discovery Pub Date : 2024-10-21 DOI: 10.1038/s41420-024-02214-w

Jingyi Zhang, Xu Zhao, Jing Tang, Ce Liu, Yining Zhang, Cheng Cai, Qingfeng Du

{"title":"Sleep restriction exacerbates cardiac dysfunction in diabetic mice by causing cardiomyocyte death and fibrosis through mitochondrial damage.","authors":"Jingyi Zhang, Xu Zhao, Jing Tang, Ce Liu, Yining Zhang, Cheng Cai, Qingfeng Du","doi":"10.1038/s41420-024-02214-w","DOIUrl":"10.1038/s41420-024-02214-w","url":null,"abstract":"Diabetic cardiomyopathy (DCM) is a cardiovascular complication of diabetes mellitus with a poor prognosis and is the leading cause of death in diabetic patients. Sleep deficiency is not only recognized as an important risk factor for the development of type 2 DM, but is also associated with increased morbidity and mortality of cardiovascular disease. The underlying role and mechanisms of sleep restriction (SR) in DCM are far from clear. The KK/Upj-Ay mouse model of T2 DM was used as a study subject, and the small animal ultrasound imaging system was used to detect the function of the heart; immunopathological staining was used to clarify the histo-structural pathological alterations of the heart; and TUNEL staining, qPCR, transmission electron microscopy (TEM), and ELISA kits were used to detect apoptosis, oxidative stress, inflammation, and mitochondrial damage, and related molecular alterations. SR led to a significant increase in mortality, cardiac hypertrophy, necrosis, glycogen deposition and fibrosis further deteriorated in DM KK mice. SR increased cardiomyocyte death in KK mice through the Bax/Bcl2 pathway. In addition to this, SR not only exacerbated the inflammatory response, but also aggravated mitochondrial damage and promoted oxidative stress in KK mice through the PRDM16-PGC-1α pathway. Overall, SR exacerbates structural alterations and dysfunction through inflammation, oxidative stress, and apoptosis in DM KK mice, increasing the risk of death. Clinicians and diabetic patients are prompted to pay attention to sleep habits to avoid accelerating the transition of DCM to heart failure and inducing death due to poor sleep habits.","PeriodicalId":9735,"journal":{"name":"Cell Death Discovery","volume":null,"pages":null},"PeriodicalIF":6.1,"publicationDate":"2024-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11494183/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142459037","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0