Isı Şoku Proteinleri: Mevcut Durum ve Gelecekteki Yönelimler

Öz

Canlılarda yaşamın sürekliliği ve hücresel olaylar, hücre içinde var olan mekanizmalar ile bu mekanizmalarda görev yapan moleküller aracılığı ile sağlanmaktadır. Organizmanın varlığını devam ettirerek çevreyle uyum içerisinde olmasının temel nedeni hücresel olaylarda rol alan moleküllerin kendi içlerinde etkileşimde olmasından kaynaklanmaktadır. Aminoasitlerin sayı, tür ve belirli diziliş şeklinde bir araya gelerek düz karakteristik bir zincirde peptid bağları ile birbirine bağlanmasıyla oluşan polipeptitlere protein adı verilmektedir. Proteinler ribozomda sentezlenir ve bu sentez sonucu polipeptitler meydana gelmektedir. Meydana gelen bu polipeptitler doğru biçimde katlanarak 3 boyutlu (3B) yapıya dönüşerek işlev kazanmaktadır Proteinler hücre olaylarındaki en önemli makromoleküllerdir Organizmada bulunan proteinlerin hatasız bir şekilde katlanması ve 3B yapısına ulaşması için yardımcı olan proteinlere “şaperon” adı verilmektedir. Birçok proteinin şaperon aktivitesine sahip olduğu ve ayrıca birçok şaperonun da stres proteini olarak görev yaptığı ve bunların en önemlisinin ısı stresine bağlı olarak artış gösteren ısı şok proteinleri (HSP) olduğu bildirilmiştir Bu derlememizde moleküler şaperonlar ve HSP hakkında bilgi verilmektedir. Ayrıca HSP’lerin yapısı ve üyeleri ayrı başlıklar altında incelenerek üyelerin özelliklerinden de bahsedilmektedir. HSP’nin görevlerinden ve Isı şok faktörlerinin özelliklerine de değinilmektedir.

Anahtar Kelimeler

• Isı şoku etkileri
• HSP (Isı şoku proteinleri)
• Moleküler şaperonlar

Etik Beyan

“Isı Şoku Proteinleri: Mevcut Durum ve Gelecekteki Yönelimler” başlıklı çalışmanın yazım sürecinde bilimsel kurallara, etik ve alıntı kurallarına uyulmuş; toplanan veriler üzerinde herhangi bir tahrifat yapılmamış ve bu çalışma herhangi başka bir akademik yayın ortamına değerlendirme için gönderilmemiştir. Bu araştırma doküman analizi ve betimsel incelemeye dayalı olarak yapıldığından etik kurul kararı zorunluluğu bulunmamaktadır.

Heat Shock Proteins: Current Status And Future Directions

Öz

The continuity of life and cellular processes in living organisms is facilitated by cellular mechanisms and the molecules that operate within these systems. The primary reason for an organism's continued existence and its harmony with the environment is the interaction of molecules involved in cellular processes. Proteins, which are polypeptides formed by the specific sequence and combination of amino acids linked by peptide bonds, are synthesized in the ribosome. These polypeptides undergo proper folding to acquire three-dimensional (3D) structures and functional capabilities. Proteins are crucial macromolecules in cellular processes. Proteins that assist other proteins in achieving flawless folding and attaining their 3D structure are termed "chaperones." It has been documented that numerous proteins exhibit chaperone activity and that many chaperones also function as stress proteins, with heat shock proteins (HSPs) being particularly significant due to their increase under heat stress. This review provides information on molecular chaperones and HSPs. Additionally, the structure and members of HSPs are examined under distinct headings, and the characteristics of these members are discussed. The functions of heat shock proteins and the attributes of heat shock factors are also addressed.

Anahtar Kelimeler

• Heat shock effects
• HSP
• Molecular chaperones

Etik Beyan

The writing process of the study titled “ Heat Shock Proteins: Current Status And Future Directions” complied with scientific rules, ethical and citation rules; no alterations were made to the collected data, and this study has not been submitted for evaluation to any other academic publication medium. Since this research is based on document analysis and descriptive examination, there is no requirement for an ethics committee decision.

Kaynakça

1. Aşkar, T. K., Ergün, N., & Turunç, V. (2007). Isı şok proteinler ve fizyolojik rolleri. Kafkas Üniversitesi Veteriner Fakültesi Dergisi, 13(1).
2. Barreto, A., Gonzalez, J. M., Kabingu, E., Asea, A., & Fiorentino, S. (2003). Stress-induced release of HSC70 from hu-man tumors. Cellular immunology, 222(2), 97-104.
3. Basu, S., & Srivastava, P. K. (2003). Fever‐like temperature induces maturation of dendritic cells through induction of hsp90. International immunology, 15(9), 1053-1061.
4. Bösl, B., Grimminger, V., & Walter, S. (2006). The molecular chaperone Hsp104—a molecular machine for protein dis-aggregation. Journal of structural biology, 156(1), 139-148.
5. Brun, C., Chevenet, F., Martin, D., Wojcik, J., Guénoche, A., & Jacq, B. (2003). Functional classification of proteins for the prediction of cellular function from a protein-protein interaction network. Genome biology, 5, 1-13.
6. Campanella, C., Pace, A., Caruso Bavisotto, C., Marzullo, P., Marino Gammazza, A., Buscemi, S., & Palumbo Piccio-nello, A. (2018). Heat shock proteins in Alzheimer’s disease: role and targeting. International Journal of Mo-lecular Sciences, 19(9), 2603.
7. Christians, E. S., Yan, L.-J., & Benjamin, I. J. (2002). Heat shock factor 1 and heat shock proteins: critical partners in protection against acute cell injury. Critical care medicine, 30(1), S43-S50.
8. Coimbra, L. B., Pinto-Martinez, A., Pavan, I. C., Melo, E. G., & Araujo, T. L. (2025). Dynamics of heat shock protein 70 kDa in heat-shocked and hypoxic human endothelial cells. Cell Stress and Chaperones, 100085.

9. Colunga Biancatelli, R. M., Solopov, P., Dimitropoulou, C., Gregory, B., Day, T., & Catravas, J. D. (2022). The heat shock protein 90 inhibitor, AT13387, protects the alveolo-capillary barrier and prevents HCl-induced chronic lung injury and pulmonary fibrosis. Cells, 11(6), 1046.
10. Colunga Biancatelli, R. M., Solopov, P., Gregory, B., & Catravas, J. D. (2021). The HSP90 inhibitor, AUY-922, protects and repairs human lung microvascular endothelial cells from hydrochloric acid-induced endothelial barrier dysfunction. Cells, 10(6), 1489.
11. Colunga Biancatelli, R. M. L., Osei-nkansah, M., Solopov, P., Day, T., Gregory, B. W., Dimitropoulou, C., & Catravas, J. D. (2023). HSP90 Inhibitors Protective Effects on Endothelial Barrier Function Are Directly Related to HSP70 Levels.
12. Deocaris, C. C., Kaul, S. C., & Wadhwa, R. (2006). On the brotherhood of the mitochondrial chaperones mortalin and heat shock protein 60. Cell stress & chaperones, 11(2), 116.
13. Doolittle, R. F. (1992). Reconstructing history with amino acid sequences 1. Protein Science, 1(2), 191-200.
14. Du, S. J., Li, H., Bian, Y., & Zhong, Y. (2008). Heat-shock protein 90α1 is required for organized myofibril assembly in skeletal muscles of zebrafish embryos. Proceedings of the National Academy of Sciences, 105(2), 554-559.
15. Ellis, R. J., & Van der Vies, S. M. (1991). Molecular chaperones. Annual review of biochemistry, 60(1), 321-347.
16. Evgen’ev, M. B. (2021). Heat shock proteins: A history of study in Russia. Cell Stress and Chaperones, 26(4), 617-627.
17. Hansen, J. J., Bross, P., Westergaard, M., Nielsen, M., Eiberg, H., Børglum, A. D.,…Gregersen, N. (2003). Genomic struc-ture of the human mitochondrial chaperonin genes: HSP60 and HSP10 are localised head to head on chromo-some 2 separated by a bidirectional promoter. Human genetics, 112, 71-77.
18. Hashemi, N., Karimpour Reyhan, S., Qahremani, R., Seifouri, K., Tavakoli, M., Seyedi, S. A.,…Nakhjavani, M. (2024). Vitamin D in Type 2 Diabetes and Its Correlation With Heat Shock Protein 70, Ferric Reducing Ability of Plas- ma, Advanced Oxidation Protein Products and Advanced Glycation End Products. Endocrinology, Diabetes & Metabolism, 7(4), e508.
19. Hoffmann, A. A., & Parsons, P. A. (1990). Evolutionary genetics and environmental stress. Oxford University Press.
20. Huot, J., Houle, F., Rousseau, S., Deschesnes, R. G., Shah, G. M., & Landry, J. (1998). SAPK2/p38-dependent F- actin reorganization regulates early membrane blebbing during stress-induced apoptosis. Journal of Cell Biology, 143(5), 1361-1373.
21. Itoh, H., Komatsuda, A., Ohtani, H., Wakui, H., Imai, H., Sawada, K. i.,…Hamada, F. (2002). Mammalian HSP60 is quickly sorted into the mitochondria under conditions of dehydration. European Journal of Biochemistry, 269(23), 5931-5938.
22. Jackson, S. E. (2013). Hsp90: structure and function. Molecular chaperones, 155-240.
23. Jung, Y. J., Melencion, S. M. B., Lee, E. S., Park, J. H., Alinapon, C. V., Oh, H. T.,…Lee, S. Y. (2015). Universal stress protein exhibits a redox-dependent chaperone function in Arabidopsis and enhances plant tolerance to heat shock and oxidative stress. Frontiers in plant science, 6, 1141.
24. Kaya, S. T. (2023). Age-and Sex-Dependent Changes in Serum Levels of TAS, TOS, TLR2, TLR4, HSP60, HSP90, and HMGB1. Konuralp Medical Journal, 15(1), 105-115.
25. Kęska, K., Szcześniak, M. W., Adamus, A., & Czernicka, M. (2021). Waterlogging-stress-responsive LncRNAs, their regulatory relationships with miRNAs and target genes in cucumber (Cucumis sativus L.). International Jour-nal of Molecular Sciences, 22(15), 8197.
26. Kim, T. Y., Lee, J. W., Kim, H.-P., Jong, H.-S., Kim, T.-Y., Jung, M., & Bang, Y.-J. (2007). DLC-1, a GTPase-activating protein for Rho, is associated with cell proliferation, morphology, and migration in human hepatocellular car-cinoma. Biochemical and biophysical research communications, 355(1), 72-77.
27. Kızmaz, M., Marakoğlu, K., Saraçlıgil, B., & Vatansev, H. (2022). Evaluation of Plasma Heat Shock Protein Levels in Smokers. Addicta: The Turkish Journal on Addictions, 9(3).
28. Laad, A. D., Thomas, M. L., Fakih, A. R., & Chiplunkar, S. V. (1999). Human gamma delta T cells recognize heat shock protein‐60 on oral tumor cells. International journal of cancer, 80(5), 709-714.
29. Lee, Y., Nagao, R. T., & Key, J. L. (1994). A soybean 101-kD heat shock protein complements a yeast HSP104 deletion mutant in acquiring thermotolerance. The Plant Cell, 6(12), 1889-1897.
30. Lindquist, S., & Craig, E. A. (1988). The heat-shock proteins. Annual review of genetics, 22(1), 631-677.
31. Liu, D., Zhang, X., Cheng, Y., Takano, T., & Liu, S. (2006). rHsp90 gene expression in response to several environmental stresses in rice (Oryza sativa L.). Plant Physiology and Biochemistry, 44(5-6), 380-386.
32. Liyanagamage, D. S. N. K., & Martinus, R. D. (2020). Role of mitochondrial stress protein HSP60 in diabetes‐ induced neuroinflammation. Mediators of inflammation, 2020(1), 8073516.
33. Macario, A. J., & de Macario, E. C. (2005). Sick chaperones, cellular stress, and disease. New England Journal of Medi-cine, 353(14), 1489-1501.
34. Mymrikov, E. V., Seit-Nebi, A. S., & Gusev, N. B. (2011). Large potentials of small heat shock proteins. Physiological reviews, 91(4), 1123-1159.
35. Nakhjavani, M., Morteza, A., Khajeali, L., Esteghamati, A., Khalilzadeh, O., Asgarani, F., & Outeiro, T. F. (2010). In- creased serum HSP70 levels are associated with the duration of diabetes. Cell Stress and Chaperones, 15(6), 959-964.
36. Nowak Jr, T. S., Bond, U., & Schlesinger, M. J. (1990). Heat shock RNA levels in brain and other tissues after hyper-thermia and transient ischemia. Journal of neurochemistry, 54(2), 451-458.
37. Ogawa, K., Seta, R., Shimizu, T., Shinkai, S., Calderwood, S. K., Nakazato, K., & Takahashi, K. (2011). Plasma adeno-sine triphosphate and heat shock protein 72 concentrations after aerobic and eccentric exercise. Exerc Immu-nol Rev, 17, 136-149.
38. Pantzartzi, C. N., Kourtidis, A., Drosopoulou, E., Yiangou, M., & Scouras, Z. G. (2009). Isolation and characterization of two cytoplasmic hsp90s from Mytilus galloprovincialis (Mollusca: Bivalvia) that contain a complex promoter with a p53 binding site. Gene, 431(1-2), 47-54.
39. Park, J., Lee, J., & Shim, K. (2023). Effects of heat stress exposure on porcine muscle satellite cells. Journal of Thermal Biology, 114, 103569.
40. Petrof, E. O., Ciancio, M. J., & Chang, E. B. (2004). Role and regulation of intestinal epithelial heat shock proteins in health and disease. Chinese journal of digestive diseases, 5(2), 45-50.
41. Pockley, A. G. (2001). Heat shock proteins in health and disease: therapeutic targets or therapeutic agents? Expert re-views in molecular medicine, 3(23), 1-21.
42. Ricaniadis, N., Kataki, A., Agnantis, N., Androulakis, G., & Karakousis, C. (2001). Long-term prognostic significance of HSP-70, c-myc and HLA-DR expression in patients with malignant melanoma. European Journal of Surgical Oncology (EJSO), 27(1), 88-93.
43. Ritossa, F. (1962). A new puffing pattern induced by temperature shock and DNP in Drosophila. Experientia, 18(12), 571-573.
44. Rossi, M. R., Somji, S., Garrett, S. H., Sens, M. A., Nath, J., & Sens, D. A. (2002). Expression of hsp 27, hsp 60, hsc 70, and hsp 70 stress response genes in cultured human urothelial cells (UROtsa) exposed to lethal and sublethal concentrations of sodium arsenite. Environmental health perspectives, 110(12), 1225-1232.
45. Rousch, J., Bingham, S., & Sommerfeld, M. (2000). PROTEIN EXPRESSION DURING HEAT STRESS IN THER-MO‐ INTOLERANT AND THERMO‐TOLERANT DIATOMS. Journal of Phycology, 36, 59-59.
46. Rylander, M. N., Feng, Y., Bass, J., & Diller, K. R. (2006). Thermally induced injury and heat‐shock protein expression in cells and tissues. Annals of the New York Academy of Sciences, 1066(1), 222-242.
47. Sayed, K. M., & Mahmoud, A. A. (2016). Heat shock protein‐70 and hypoxia inducible factor‐1α in type 2 diabetes mellitus patients complicated with retinopathy. Acta ophthalmologica, 94(5), e361-e366.
48. Schirmer, E. C., Glover, J. R., Singer, M. A., & Lindquist, S. (1996). HSP100/Clp proteins: a common mechanism ex-plains diverse functions. Trends in biochemical sciences, 21(8), 289-296.
49. Sergio, E., Cobianchi, R. C., Sorbo, S., Conte, B., & Basile, A. (2007). Ultrastructural alterations and HSP 70 induction in Elodea ca-nadensis Michx. exposed to heavy metals. Caryologia, 60(1-2), 115-120.
50. Shevtsov, M., & Multhoff, G. (2016). Heat shock protein–peptide and HSP-based immunotherapies for the treatment of cancer. Frontiers in immunology, 7, 171.
51. Sørensen, J. G., Kristensen, T. N., & Loeschcke, V. (2003). The evolutionary and ecological role of heat shock proteins. Ecology letters, 6(11), 1025-1037.
52. Sun, Y., & MacRae, T. (2005). Small heat shock proteins: molecular structure and chaperone function. Cellular and Molecular Life Sciences CMLS, 62, 2460-2476.
53. Tissiéres, A., Mitchell, H. K., & Tracy, U. M. (1974). Protein synthesis in salivary glands of Drosophila melanogaster: relation to chromosome puffs. Journal of molecular biology, 84(3), 389-398.
54. Trivedi, V., Gadhvi, P., Chorawala, M., & Shah, G. (2010). Role of heat shock proteins in immune response and immu-notherapy for human cancer. Int J Pharm Sci Rev Res, 2, 57-62.
55. Tsan, M.-F., & Gao, B. (2009). Heat shock proteins and immune system. Journal of Leucocyte Biology, 85(6), 905-910.
56. Tutar, L., & Tutar, Y. (2010). Heat shock proteins; an overview. Current Pharmaceutical Biotechnology, 11(2), 216-222.
57. Tytell, M., & Hooper, P. L. (2001). Heat shock proteins: new keys to the development of cytoprotective therapies. Emerging Therapeutic Targets, 5(2), 267-287.
58. Vickers, N. J. (2017). Animal communication: when i’m calling you, will you answer too? Current biology, 27(14), R713-R715.
59. Voss, M. R., Stallone, J. N., Li, M., Cornelussen, R. N., Knuefermann, P., & Knowlton, A. A. (2003). Gender differences in the expression of heat shock proteins: the effect of estrogen. American Journal of Physiology- Heart and Cir-culatory Physiology, 285(2), H687-H692.
60. Walker, V. E., Wong, M. J., Atanasiu, R., Hantouche, C., Young, J. C., & Shrier, A. (2010). Hsp40 chaperones promote degradation of the HERG potassium channel. Journal of Biological Chemistry, 285(5), 3319-3329.
61. Wang, W., Vinocur, B., Shoseyov, O., & Altman, A. (2004). Role of plant heat-shock proteins and molecular chaperones in the abiotic stress response. Trends in plant science, 9(5), 244-252.
62. Wang, X., Zhang, H., Xie, Q., Liu, Y., Lv, H., Bai, R.,…Guo, Y.-D. (2020). SlSNAT interacts with HSP40, a molecular chaperone, to regulate melatonin biosynthesis and promote thermotolerance in tomato. Plant and Cell Physi-ology, 61(5), 909-921.
63. Wu, J., Liu, T., Rios, Z., Mei, Q., Lin, X., & Cao, S. (2017). Heat shock proteins and cancer. Trends in pharmacological sciences, 38(3), 226-256.
64. Wu, S., Zhao, Y., Wang, D., & Chen, Z. (2023). Mode of action of heat shock protein (HSP) inhibitors against viruses through host HSP and virus interactions. Genes, 14(4), 792.
65. Xu, Y., Hu, W., & Zhou, G. (2025). Role of heat shock protein in radiation-induced effect and related potential clinical application. Radiation Medicine and Protection, 6(01), 51-60.
66. Young, D. B., & Garbe, T. R. (1991). Heat shock proteins and antigens of Mycobacterium tuberculosis. Infection and immunity, 59(9), 3086-3093.
67. Zininga, T., Ramatsui, L., & Shonhai, A. (2018). Heat shock proteins as immunomodulants. Molecules, 23(11), 2846.
68. Zuo, D., Subjeck, J., & Wang, X.-Y. (2016). Unfolding the role of large heat shock proteins: new insights and therapeutic implications. Frontiers in immunology, 7, 75.