![]() ![]() ![]() The high molecular weight HSPs which range from 60 to 110 kDa are ATP-dependent and their primary cellular function is binding and folding of nascent proteins through ATP-dependent allosteric organization, even though assembling, transportation, vaccination against cancer metastasis, and degradation of improperly-folded peptides have also been reported. Molecular chaperones, which are found in all living cells and form part of the defence system against both internal and external stressors, are primarily grouped into two major groups according to their amino acid composition, molecular weight, as well as their specific cellular function as the high molecular weight and the small molecular weight HSPs. Upon discovering these proteins, it is not surprising that HSPs have made a very large impact in various areas of research, including medical and biological fields, because of their diverse functions in both pathological and normal conditions. Since the discovery of heat shock proteins in 1962 by Ritossa in the salivary glands of the Drosophila larvae, the important functions of heat shock proteins in response to various stressful signals including human cancer and cystic fibrosis, has been well elucidated. Some of these constitutively-expressed heat shock polypeptides are involved in protein folding and translocation of organelles across cellular membranes, prompting many authors to label them “molecular chaperones”. These responses enable cellular protection against protein denaturation and possible degradation of misfolded proteins, which may, in turn, result in protein aggregation and cancer. These stressors include heat, nutrient deficiency, oxidative stress, acute or chronic inflammatory diseases, viral infections, ischemia, heavy metals, exercise, gravity, and bacterial infections. We propose that careful induction of HSPs in HIDs and cancer, especially prior to inflammation, will provide good therapeutics in the management and treatment of HIDs and cancer.Īlthough some heat shock proteins (HSPs) are constitutively produced, most are molecular chaperones that are normally over-expressed by cells in response to inducible signals that may lead to protein denaturation. HSPs are known to modulate the effects of inflammation cascades leading to the endogenous generation of ROS and intrinsic apoptosis through inhibition of pro-inflammatory factors, thereby playing crucial roles in the pathogenesis of HIDs and cancer. Hence, there is a need to maintain careful balance between the oxidant-antioxidant inflammatory status in the human body. Therefore, it becomes apparent that the interplay between oxidant-apoptosis-inflammation is critical in the dysfunction of the antioxidant system and, most importantly, in the progression of HIDs. Under normal physiological conditions, ROS levels and inflammatory reactions are kept in check for the cellular benefits of fighting off infectious agents through antioxidant mechanisms however, this balance can be disrupted under pathological conditions, thus leading to oxidative stress and massive cellular destruction. Excessive apoptosis, resulting from increased reactive oxygen species (ROS) cellular levels and subsequent amplified inflammatory reactions, is well known in the pathogenesis and progression of several human inflammatory diseases (HIDs) and cancer. Heat shock proteins (HSPs) play cytoprotective activities under pathological conditions through the initiation of protein folding, repair, refolding of misfolded peptides, and possible degradation of irreparable proteins. ![]()
0 Comments
Leave a Reply. |