Miova Biljana, Dimitrovska Maja, Dinevska-Kjovkarovska Suzana, Esplugues Juan V, Apostolova Nadezda
Facultad de Ciencias de la Salud, Universitat Jaume I, Av. Vicent Sos Baynat, s/n, Castelló de la Plana 12071, Spain.
Curr Pharm Des. 2016;22(18):2619-39. doi: 10.2174/1381612822666160203114738.
Heat preconditioning is a rapid cellular adaptive mechanism shared by many cells/ organs / organisms that results in synthesis and accumulation of heat shock proteins (HSPs), which are responsible for increased tolerance and survival of animals during and after heat stress (HS). HSPs function as molecular chaperones by restoring cellular homeostasis and promoting cell survival, and their major functions include protection of cells from injury by preventing protein damage and aggregation. Abundant evidence points to the ability of one kind of stress caused by external factors that induce primary adaptations in the organism to provide protection against additional stress of the same or another type, a phenomenon known as cross-tolerance. Diabetes mellitus (DM) is one of the diseases which have been associated with increased tissue sensitivity and vulnerability due to incorrect protein folding. Thus, HSPs may play an important role in minimizing the protein damage that can occur under the stressful conditions created by the disease. By increasing HSP production, heat preconditioning may be a promising therapy for patients with lifestylerelated diseases such as hypercholesterolemia, hypertension, DM and obesity. Also, pancreatic β-cells exposed to acute HS activate defence mechanisms which include HSP synthesis and are less sensitive to the effects of cytotoxic agents such as NO, oxygen radicals and β-cytotoxic diabetogenic agents, such as streptozotocin (STZ). Mitochondrial dysfunction and mitochondria-specific cell stress are associated and can even be a primary abnormality caused by DMinduced hyperglycaemia and oxidative stress. There are an increasing number of genetic and/or pharmacological modulations of HSPs that have revealed the connection between HSPs, mitochondria and diabetes. HSPs may affect mitochondrial function in multiple ways, but the influence on skeletal muscle and adipose tissue, as well as on the pancreas, has attracted most interest as a key element in the development of novel pharmacological approaches to treating DM and associated metabolic conditions.
热预处理是许多细胞/器官/生物体共有的一种快速细胞适应性机制，可导致热休克蛋白（HSPs）的合成和积累，这些蛋白负责提高动物在热应激（HS）期间及之后的耐受性和存活率。HSPs通过恢复细胞内稳态和促进细胞存活发挥分子伴侣的作用，其主要功能包括通过防止蛋白质损伤和聚集来保护细胞免受损伤。大量证据表明，由外部因素引起的一种应激能够诱导生物体产生初级适应性，从而为抵御相同或另一种类型的额外应激提供保护，这一现象称为交叉耐受性。糖尿病（DM）是一种与由于蛋白质错误折叠导致的组织敏感性和脆弱性增加相关的疾病。因此，HSPs可能在将疾病所造成的应激条件下可能发生的蛋白质损伤降至最低方面发挥重要作用。通过增加HSP的产生，热预处理可能是一种有前景的治疗方法，适用于患有诸如高胆固醇血症、高血压、糖尿病和肥胖症等与生活方式相关疾病的患者。此外，暴露于急性热应激的胰腺β细胞会激活包括HSP合成在内的防御机制，并且对细胞毒性剂（如一氧化氮、氧自由基）以及β细胞毒性致糖尿病剂（如链脲佐菌素（STZ））的作用不太敏感。线粒体功能障碍和线粒体特异性细胞应激相互关联，甚至可能是糖尿病诱导的高血糖和氧化应激导致的主要异常。对HSPs进行的遗传和/或药理学调节越来越多，这些调节揭示了HSPs、线粒体与糖尿病之间的联系。HSPs可能以多种方式影响线粒体功能，但对骨骼肌、脂肪组织以及胰腺的影响作为治疗糖尿病及相关代谢病症的新型药理学方法开发中的关键因素，引起了人们的最大兴趣。
