Li Sha, Li Qixiu, Xiang Hong, Wang Chenye, Zhu Qi, Ruan Danping, Zhu Yi Zhun, Mao Yicheng
Department of Pharmacology, School of Pharmacy, Minhang Hospital, Fudan University, Shanghai, China.
School of Pharmacy and State Key Laboratory for the Quality Research of Chinese Medicine, Macau University of Science and Technology, Macau, China.
Antioxid Redox Signal. 2025 Mar;42(7-9):301-320. doi: 10.1089/ars.2024.0605. Epub 2024 Sep 26.
S-propargyl-cysteine (SPRC) is an endogenous hydrogen sulfide (HS) donor obtained by modifying the structure of S-allyl cysteine in garlic. This study aims to investigate the effect of SPRC on mitigating cardiac aging and the involvement of jumonji domain-containing protein 3 (JMJD3), a histone demethylase, which represents the primary risk factor in major aging related diseases, in this process, elucidating the preliminary mechanism through which SPRC regulation of JMJD3 occurs. , SPRC mitigated the elevated levels of reactive oxygen species, senescence-associated β-galactosidase, p53, and p21, reversing the decline in mitochondrial membrane potential, which represented a reduction in cellular senescence. , SPRC improved Dox-induced cardiac pathological structure and function. Overexpression of JMJD3 accelerated cardiomyocytes and cardiac senescence, whereas its knockdown reduced the senescence phenotype. The potential binding site of the upstream transcription factor of JMJD3, sheared X box binding protein 1 (XBP1s), was determined using online software. SPRC promoted the expression of cystathionine γ-lyase (CSE), which subsequently inhibited the IRE1α/XBP1s signaling pathway and decreased JMJD3 expression. This study is the first to establish JMJD3 as a crucial regulator of cardiac aging. SPRC can alleviate cardiac aging by upregulating CSE and inhibiting endoplasmic reticulum stress pathways, which in turn suppress JMJD3 expression. JMJD3 plays an essential role in cardiac aging regulation, whereas SPRC can suppress the expression of JMJD3 by upregulating CSE, thus delaying cardiac aging, which suggests that SPRC may serve as an aging protective agent, and pharmacological targeting of JMJD3 may also be a promising therapeutic approach in age-related heart diseases. 42, 301-320.
S-炔丙基半胱氨酸（SPRC）是一种内源性硫化氢（HS）供体，通过修饰大蒜中的S-烯丙基半胱氨酸结构获得。本研究旨在探讨SPRC对减轻心脏衰老的作用以及含jumonji结构域蛋白3（JMJD3，一种组蛋白去甲基化酶，是主要衰老相关疾病的主要危险因素）在此过程中的参与情况，阐明SPRC调节JMJD3的初步机制。SPRC减轻了活性氧、衰老相关β-半乳糖苷酶、p53和p21水平的升高，逆转了线粒体膜电位的下降，这代表细胞衰老的减轻。SPRC改善了阿霉素诱导的心脏病理结构和功能。JMJD3的过表达加速了心肌细胞和心脏衰老，而其敲低则减少了衰老表型。使用在线软件确定了JMJD3上游转录因子剪切型X盒结合蛋白1（XBP1s）的潜在结合位点。SPRC促进了胱硫醚γ-裂解酶（CSE）的表达，随后抑制了IRE1α/XBP1s信号通路并降低了JMJD3的表达。本研究首次将JMJD3确立为心脏衰老的关键调节因子。SPRC可通过上调CSE和抑制内质网应激途径来减轻心脏衰老，进而抑制JMJD3的表达。JMJD3在心脏衰老调节中起重要作用，而SPRC可通过上调CSE抑制JMJD3的表达，从而延缓心脏衰老，这表明SPRC可能作为一种衰老保护剂，并且针对JMJD3的药物靶向治疗也可能是治疗年龄相关性心脏病的一种有前景的治疗方法。42, 301 - 320。
