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LDHA Desuccinylase sirtuin 5 as A Novel Cancer Metastatic Stimulator in Aggressive Prostate Cancer

Genomics, Proteomics & Bioinformatics 2023年第1期21卷 177-189页

作者： Oh Kwang Kwon In Hyuk Bang So Young Choi Ju Mi Jeon Ann-Yae Na Yan Gao Sam Seok Cho Sung Hwan Ki Youngshik Choe Jun Nyung Lee Yun-Sok Ha Eun Ju Bae Tae Gyun Kwon Byung-Hyun Park Sangkyu Lee BK21 Plus KNU Multi-Omics Based Creative Drug Research Team College of PharmacyResearch Institute of Pharmaceutical SciencesKyungpook National UniversityDaegu 41566Republic of Korea Department of Biochemistry and Molecular Biology Chonbuk National University Medical SchoolJeonjuJeonbuk 54896Republic of Korea College of Pharmacy Chosun UniversityGwangju 61452Republic of Korea Korea Brain Research Institute Daegu 41068Republic of Korea Department of Urology School of MedicineKyungpook National UniversityDaegu 41566Republic of Korea Department of Urology Kyungpook National University HospitalDaegu 41566Republic of Korea College of Pharmacy Chonbuk UniversityJeonjuJeonbuk 54896Republic of Korea School of Pharmacy Sungkyunkwan UniversitySuwon 16419Republic of Korea

Prostate cancer(PCa)is the most commonly diagnosed genital cancer in men *** 80%of the patients who developed advanced PCa suffered from bone metastasis,with a sharp drop in the survival *** great efforts,the detailed mechanisms underlying castration-resistant PCa(CRPC)remain *** 5(SIRT5),an NAD+-dependent desuccinylase,is hypothesized to be a key regulator of various ***,compared to other SIRTs,the role of SIRT5 in cancer has not been extensively ***,we revealed significantly decreased SIRT5 levels in aggressive PCa cells relative to the PCa *** correlation between the decrease in the SIRT5 level and the patient’s reduced survival rate was also *** quantitative global succinylome analysis,we characterized a significant increase in the succinylation at lysine 118(K118su)of lactate dehydrogenase A(LDHA),which plays a role in increasing LDH *** a substrate of SIRT5,LDHA-K118su significantly increased the migration and invasion of PCa cells and LDH activity in PCa *** study reveals the reduction of SIRT5 protein expression and LDHA-K118su as a novel mechanism involved in PCa progression,which could serve as a new target to prevent CPRC progression for PCa treatment.

关键词： sirtuin 5 Lactate dehydrogenase A Lysine succinylation PCa progression

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Succinylation modification:a potential therapeutic target in stroke

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Neural Regeneration Research 2024年第4期19卷 781-787页

作者： Jie Lian Wenwu Liu Qin Hu Xiaohua Zhang Department of Neurosurgery Ren Ji HospitalShanghai Jiao Tong University School of Medicine Department of Diving and Hyperbaric Medicine Naval Medical CenterNaval Medical University

Stroke is a leading cause of mortality and disability *** cell death triggered by the compromised supply of blood oxygen and glucose is one of the major pathophysiology of strokeinduced brain *** mitochondrial energy metabolism is observed minutes after stroke and is closely associated with the progression of ***,a new type of posttranslational modification,known as lysine succinylation,has been recognized to play a significant role in mitochondrial energy metabolism after ***,the role of succinylation modification in cell metabolism after stroke and its regulation are not well *** aimed to review the effects of succinylation on energy metabolism,reactive oxygen species generation,and neuroinflammation,as well as sirtuin 5 mediated desuccinylation after *** also highlight the potential of targeting succinylation/desuccinylation as a promising strategy for the treatment of *** succinylation level is dynamically regulated by the nonenzymatic or enzymatic transfer of a succinyl group to a protein on lysine residues and the removal of succinyl catalyzed by *** evidence has suggested that succinylation can regulate the metabolic pathway through modulating the activity or stability of metabolic ***,especially sirtuin 5,are characterized for their desuccinylation activity and have been recognized as a critical regulator of metabolism through desuccinylating numerous metabolic *** between succinylation and desuccinylation has been implicated in the pathophysiology of *** agents that enhance the activity of sirtuin 5 have been employed to promote desuccinylation and improve mitochondrial metabolism,and neuroprotective effects of these agents have been observed in experimental stroke ***,their therapeutic efficacy in stroke patients should be validated.

关键词： mitochondria metabolism neuroprotection sirtuin 5 stroke succinylation modification

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SIRT5对高糖环境下结肠癌细胞增殖、凋亡、迁移的影响及机制探讨

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天津医药 2020年第9期48卷 818-823页

作者：贺帅岳淑芬周蕾齐琦包头医学院病理学教研室包头医学院第一附属医院病理科014060 包头医学院组织学与胚胎学教研室包头医学院病原生物与免疫学实验室包头医学院

目的探讨sirtuin5(SIRT5)对高糖环境下Lovo细胞增殖、凋亡及迁移的影响及可能机制。方法高糖培养基(葡萄糖含量4500 mg/L)及普通培养基(葡萄糖含量2000 mg/L)培养SIRT5高表达的人结肠癌Lovo细胞,进行慢病毒转染实验,高糖培养基及普通培... 详细信息

目的探讨sirtuin5(SIRT5)对高糖环境下Lovo细胞增殖、凋亡及迁移的影响及可能机制。方法高糖培养基(葡萄糖含量4500 mg/L)及普通培养基(葡萄糖含量2000 mg/L)培养SIRT5高表达的人结肠癌Lovo细胞,进行慢病毒转染实验,高糖培养基及普通培养基各分为空白对照组(MOCK组,无干预)、阴性对照组(NC组,对照RNAi慢病毒转染)和SIRT5-RNAi组(KD组,SIRT5-RNAi慢病毒转染),用MTT法检测各组细胞1~5 d增殖能力变化,AnnexinⅤ检测各组细胞凋亡率,划痕实验法检测各组细胞迁移率;应用实时荧光定量PCR(qPCR)检测各组细胞SIRT5、哺乳动物雷帕霉素靶蛋白(mTOR)、缺氧诱导因子-1α(HIF-1α)、M2型丙酮酸激酶(PKM2)及己糖激酶-2(HK2)mRNA的表达变化,Western blot检测各组上述指标的蛋白表达水平。结果高糖培养基中,KD组与NC组、MOCK组比较,3~5 d时增殖水平降低,凋亡率增加,而24 h迁移率降低(P5),且SIRT5、mTOR、HIF-1α、PKM2及HK2 mRNA及蛋白的相对表达水平均明显降低(P5)。普通培养基中,KD组与NC及MOCK组比较,1~4 d时增殖水平差异无统计学意义,5 d时增殖水平降低(P5),24 h凋亡率差异无统计学意义。结论高糖环境下,SIRT5可能通过影响糖代谢关键酶HK2及mTOR/HIF-1α/PKM2信号通路调控糖酵解,从而促进结肠癌的发生、发展。

关键词：结肠肿瘤细胞系,肿瘤抗衰老酶缺氧诱导因子1,α亚基丙酮酸激酶己糖激酶高糖哺乳动物雷帕霉素靶蛋白 sirtuin 5

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