Uncovering the Therapeutic Potential of Phosphocreatine in Diabetic Retinopathy: Mitigating Mitochondrial Dysfunction and Apoptosis via JAK2/STAT3 Signaling Pathway

被引:5
作者
Qaed, Eskandar [1 ,2 ]
Alyafeai, Eman [3 ]
Al-Maamari, Ahmed [4 ]
Zaky, Mohamed Y. [5 ]
Almoiliqy, Marwan [1 ]
Al-Hamyari, Bandar [6 ,7 ]
Qaid, Abdullah [8 ]
Yafei, Saeed [1 ]
Aldahmash, Waleed [9 ]
Mahyoub, Mueataz A. [10 ]
Wang, Fuhan [1 ]
Kang, Le [1 ]
Tang, Zeyao [1 ]
Zhang, Jianbin [1 ]
机构
[1] Dalian Med Univ, Dept Pharmacol, West Sect 9,South Rd Lushun, Dalian 116044, Peoples R China
[2] Lanzhou Univ, Coll Chem & Chem Engn, State Key Lab Appl Organ Chem, Key Lab Nonferrous Met Chem & Resources Utilizat G, Lanzhou 730000, Peoples R China
[3] Wenzhou Med Univ, Sch Pharmaceut Sci, Wenzhou, Peoples R China
[4] Hebei Med Univ, Minist Educ,Dept Pharmacol, Key Lab Neural & Vasc Biol, Key Lab New Drug Pharmacol & Toxicol, Shijiazhuang, Peoples R China
[5] Beni Suef Univ, Fac Sci, Zool Dept, Mol Physiol Div, POB 62521, Bani Suwayf, Egypt
[6] Lanzhou Univ, Sch Pharm, Lanzhou 730000, Peoples R China
[7] Lanzhou Univ, State Key Lab Appl Organ Chem, Lanzhou 730000, Peoples R China
[8] NI Pirogov Russian Natl Res Med Univ, Moscow, Russia
[9] King Saud Univ, Coll Sci, Zool Dept, POB 2455, Riyadh 11451, Saudi Arabia
[10] Xi An Jiao Tong Univ, Affiliated Hosp 1, Dept Gastroenterol, Xian, Peoples R China
关键词
Diabetic retinopathy (DR); Mitochondria (mt); Phosphocreatine (PCr); High-resolution respirometry (HRR); JAK2/STAT3; Apoptosis; HIGH-RESOLUTION RESPIROMETRY; OXIDATIVE STRESS; CELLS; DAMAGE;
D O I
10.1007/s12031-023-02175-2
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Diabetic retinopathy (DR) stands as a prevalent complication of diabetes mellitus, causing damage to the delicate retinal capillaries and potentially leading to visual impairment. While the exact underlying cause of DR remains elusive, compelling research suggests that mitochondrial energy deficiency and the excessive generation of reactive oxygen species (ROS) play pivotal roles in its pathogenesis. Recognizing that controlling hyperglycemia alone fails to reverse the defects in retinal mitochondria induced by diabetes, current strategies seek to restore mitochondrial function as a means of safeguarding against DR. To address this pressing issue, a comprehensive study was undertaken to explore the potential of phosphocreatine (PCr) in bolstering mitochondrial bioenergetics and providing protection against DR via modulation of the JAK2/STAT3 signaling pathway. Employing rat mitochondria and RGC-5 cells, the investigation meticulously assessed the impact of PCr on ROS production, mitochondrial membrane potential, as well as the expression of crucial apoptotic and JAK2/STAT3 signaling pathway proteins, utilizing cutting-edge techniques such as high-resolution respirometry and western blotting. The remarkable outcomes revealed that PCr exerts a profound protective influence against DR by enhancing mitochondrial function and alleviating diabetes-associated symptoms and biochemical markers. Notably, PCr administration resulted in an upregulation of antiapoptotic proteins, concomitant with a downregulation of proapoptotic proteins and the JAK2/STAT3 signaling pathway. These significant findings firmly establish PCr as a potential therapeutic avenue for combating diabetic retinopathy. By augmenting mitochondrial function and exerting antiapoptotic effects via the JAK2/STAT3 signaling pathway, PCr demonstrates promising efficacy both in vivo and in vitro, particularly in counteracting the oxidative stress engendered by hyperglycemia. In summary, our study sheds light on the potential of PCr as an innovative therapeutic strategy for diabetic retinopathy. By bolstering mitochondrial function and exerting protective effects via the modulation of the JAK2/STAT3 signaling pathway, PCr holds immense promise in ameliorating the impact of DR in the face of oxidative stress induced by hyperglycemia.
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页数:17
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