Reviews in Agricultural Science
Online ISSN : 2187-090X
Heat Shock Protein 70 and Its Role in Alleviating Heat Stress and Improving Livestock Performance
Israa L. AL-Jaryan, Tahreer M. AL-Thuwaini, Hashim H. AL-Jebory
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Keywords: heat shock protein 70, heat stress, livestock, thermoregulation
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2023 Volume 11 Pages 234-242

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Abstract

Varieties of proteins are induced in livestock when exposed to environmental stress, among them are heat shock proteins (HSPs). HSPs are proteins that provide antioxidant protection in cells as well as thermotolerance. They function as chaperones, helping to fold, unfold, and refold stress-denatured proteins. Further, HSPs represent one of the most important physiological parameters for thermotolerance in livestock. This review aims to highlight the importance of heat shock protein 70 in livestock performance under heat stress. HSP types and functions are reviewed briefly with a focus on HSP70. Furthermore, this review examines the relationship between HSP70 and thermal adaptation to heat stress. Also discussed is the correlation of a high concentration of HSP70 with improved performance in livestock. HSP70 can improve animal performance by serving as a crucial factor in the adaptation process for livestock. Identifying and utilizing thermotolerant genotypes is imperative for improving livestock productivity and reproduction. For this reason, highlighting the importance of HSP70 for increasing livestock performance is valuable, and further molecular studies are necessary to determine their effectiveness.

1. Introduction

Livestock provides livelihood and food security to more than a million people globally, although climate change has become one of the most significant threats to livestock [1, 2]. A body responds to hot stimuli by altering its homeostasis and modifying the physio-biochemical characteristics of livestock [3, 4]. This extreme heat can adversely affect animal performance and welfare [5, 6], reducing food security, and having restrictive effects on productive and reproductive traits in livestock [7]. It triggers apoptosis in poultry intestinal epithelial cells by accumulating free radicals that cause reduced feed efficiency and suppress nutrient transporters that negatively affect growth performance and cause severe poultry production losses [8]. In cattle, increasing the temperature during the follicular growth or maturation phase may accelerate the aging process and reduce the fertility of the bovine oocytes [9]. Moreover, heat stress makes lactating bovine utilize systemic amino acids more efficiently, resulting in a limited supply of amino acids to the mammary gland for milk protein synthesis, hence, altering protein synthesis [10].

Animals under heat stress preferentially express several proteins, including heat shock proteins (HSPs) [6]. Upon discovery, HSP synthesis appeared to be triggered not only by heat but also by inflammatory and cold stress, along with salinity [11]. HSP represents one of the crucial physiological parameters for livestock under stress and is essential for making animals more adaptive [12]. By activating heat and other stresses, HSP confers thermotolerance on cells and the ability to survive during injury and oxidative stress, prevent apoptosis and transform heat into heat resistance [13]. The HSPs perform these functions by interacting with denatured proteins and preventing the accumulation of toxic protein aggregates in the cells [13]. Additionally, it is critical for proper protein folding and can protect proteins from misfolding without becoming part of their final structure [15]. Changing the configuration of proteins can alter critical processes and exacerbate protein misfolding [16]. Misfolded proteins can clump together and become aggregates that prevent them from moving into their proper conformation, cause cellular toxicity and contribute to cellular proteostatic collapse that negatively impacts livestock production and reproduction [17]. As a result, an effort is being made in this review to signify the importance of heat shock proteins 70 in alleviating heat stress and improving livestock performance under heat stress.

2. Heat shock protein 70 and thermotolerance of livestock

Heat stress affects many parts of the world, which reduces animal production and reproduction and makes them more susceptible to disease [18]. When cells are stressed, their membrane fluidity may be disturbed, causing the activation of various signal transduction pathways, which in turn can trigger heat shock responses [19]. Heat shock factor-1 (HSF-1) is the primary transcription factor activated by stress in vertebrates that appears to be activated by denatured proteins in the cytosol as the first step in the stress response. When phosphorylated HSF-1 forms triplicates, it moves into the nucleus, which binds to the heat shock element and induces the expression of HSP genes [20]. Heat shock proteins encoded by these genes protect cells against heat stress through a variety of mechanisms including regulating cellular redox conditions, modulating apoptosis, antiapoptosis signaling and developing thermotolerance. These functions depend on HSPs’ ability to act as molecular chaperones to prevent misfolded and non-native proteins from aggregating [21]. A chaperone function of HSPs is to ensure that denatured proteins fold, unfold, and refold in response to stress [22]. By reducing damage or abnormal accumulation of polypeptides and instructing newly synthesized polypeptides to be packaged, degraded, or repaired [23], it provides a cell with thermotolerance and the ability to deal with injury and oxidative stress. As a result of these activities, misfolded proteins can be detected and corrected, and nascent polypeptides could assemble post-translationally [24]. Additionally, HSP70’s function in redox homeostasis interplays with its protective function, preventing oxidative stress through interaction with protein substrates involved in the process [25]. Varieties of HSPs families are characterized by their molecular weights and their biological functions (HSP110, HSP100, HSP90, HSP70, HSP60, HSP40, HSP10 and small HSP families), in which thermotolerance development in livestock animals is associated primarily with HSP70 [26].

The HSP70 is one of the most abundant HSP families in livestock that plays a vital role in coping with environmental stress and achieving thermal comfort [27]. Most eukaryotic genomes contain the conserved HSP70 family with 52–99% amino acid identity [28]. HSP70 proteins have three domains: an N-terminal nucleotide-binding domain, a substrate-binding domain that binds hydrophobic amino acids, and an α-helical domain at the C-terminus (the least conserved region) [29]. HSP70s perform all their functions through transient interactions with substrate proteins via their C-terminal substrate-binding domains (SBDs) [30]. Additionally, HSP70 interacts with the HSP90 system to regulate eukaryotic heat shock responses [31] and regulates apoptosis [13]. These proteins protect against hyperthermia and other stressful conditions by balancing protein production and degradation [32]. Besides, HSP70 is required to maintain optimal growing conditions, remove protein aggregates via solubilization, degrade proteins via proteasomes and autophagy, assemble and disassemble protein complexes [33] and plays a crucial role in protein unfolding in the cytosol and membrane-bound organelles [34]. Moreover, HSP70 proteins mediate the release of endocytosed clathrin-coated vesicles and the transfer of organelle-specific proteins to the appropriate translocation machinery [30]. HSP70 has also been shown to serve as a molecular chaperone for quantifying livestock’s heat stress response [35], maintaining a balance between protein synthesis and degradation [32] while protecting hyperthermia and other stressors [23, 36, 37]. Various studies have examined the role of HSP70 in preventing the denaturation of proteins by serving as a molecular chaperone and a cell protector [22, 38]. Sheep, buffaloes, cattle, broilers, goats and pigs exhibit elevated HSP70 expression under heat stress, thus improving their adaptation [22, 38, 39, 40, 41]. This elevated HSP70 expression is necessary to maintain homeostasis and contribute to adaptation to heat [7, 42]. Redox homeostasis is closely related to HSP70 in several ways, including functional regulation of HSP70 by cysteine modifications, oxidative stress-induced HSP70 expression, proteostasis involving Hsp70 under oxidative stress, and redox-related signaling pathways [43]. Animals living in tropical and arid climates are protected from heat stress by these proteins. Without this protective shield, animals become vulnerable to the adverse effects of heat stress [42, 43].

3. Heat shock protein 70 polymorphism and livestock performance

There is genetic evidence that sheep [44, 45], goats [46], cattle [47], pigs [48] and poultry [49] can adapt to living in heat-stressed environments. When cells undergo extreme heat stress, heat shock factors (HSFs) activate thermo-resistant genes such as HSPs, and their expression increases [50]. The HSP70 gene is one of the most conserved and abundant genes in the HSP family associated with stress response [51], and a change in this gene expression is among the genetic adaptations shown by animals to adapt to heat stress [52]. A key concern for researchers is finding genetic polymorphism associated with heat tolerance. A study by Singh et al. [53] evaluated the association between polymorphisms of HSP70 and HSP90 genes and adaptive traits among Indian sheep (Ovis aries) in peripheral blood mononuclear cells. In addition, several HSP genes, including HSP32, HSP40, HSP60, HSP70, HSP90, HSP110, and others, are also expressed during hyperthermic stress in peripheral blood mononuclear cells of goats [27, 38, 42]. A study conducted on dairy cattle by Cai et al. [54] revealed that cattle with AC genotype expressed more HSP70 mRNA at 37.5 °C and showed lower levels of apoptosis in lymphocytes of peripheral blood. The effect may occur because HSP repairs proteins and inhibits apoptosis in damaged cells by preventing caspase 3 activation and reducing cellular protein synthesis [55, 56]. In addition, single nucleotide polymorphisms (SNPs) (g.895 C/- and g.1128 G/T) in the 5’-UTR region of inducible HSP70.1 alleviate heat stress response during the exposure to heat stress at 43 °C in lactating Holstein cows [57]. In this regard, studying promoter variants of the HSP70.1 gene in Frieswal crossbred cattle by Deb et al. [58] revealed that the HSP70.1 gene is polymorphic and could be used to select dairy cattle with higher milk production and better thermotolerance. The CC genotypes of the HSP70.1 gene showed a decrease in the average rectal temperature and the respiratory rate and a substantial increase in heat tolerance coefficient (HTC) for C−genotypic variants. A possible explanation is that heat stress results in a negative energy balance, causing dairy cattle to produce less milk because their normal secretory functions are affected [59]. Thus, mammary glands produce more HSPs under heat stress to protect and maintain their cells. Bhat et al. [23] reported that genotype AA of Tharparkar cattle demonstrated the greatest thermotolerance and HTC with a G > T SNP in the HSP70 gene at position 149th. Additionally, 43 SNPs and three indels found within the 5’ UTR region of the HSP70.1 gene in Holstein Friesian cattle breeds revealed an association with stress tolerance [60]. Further, there is an association between genetic polymorphism in the promoter region of HSP70 at positions 895, 1,125 and 1,128 and calving traits in crossbred Brahman cattle [47]. Cattle with increased HSP70 expression exhibit higher pregnancy and calf weaning weights and higher fertility scores [24]. These could indicate that the HSP70 protein plays a role in the post-translational folding and transport of proteins through the membrane, which is crucial in the development of early embryos and the fertilization processes. Besides, Murrah buffaloes have significantly higher levels of HSP70 following dry heat exposure (42 °C with existing relative humidity) than those in control conditions [40]. Based on a study by Jin et al. [48], HSP70 genotypes K1-AB and K3-BB have been associated with increased carcass weight and backfat thickness in Korean pigs. The increased expression of HSP70 could have significantly contributed to the ability of pig tissues in preserving the quality and functionality of their proteins, thus demonstrating their remarkable ability to adapt to heat stress with better productivity [41].

In chicken, HSP25, HSP70, HSP90AA1, and HSPA2 show increased expression in the testes of heat-stressed chickens [49]. SNPs in the 5’-flanking region (C.-69A>G) of the HSP70 gene and their association with heat tolerance (15 °C) are reported in local chickens in which only chickens with genotype GG showed heat stress resistance [61]. In Mazandaran native breeder poultry, a novel SNP (A179C) is identified in the coding region of the HSP70 gene that has shown a significant effect on growth traits, fertility, and hatchability [62]. Poultry carrying specific HSP70 genotypes are heat tolerant and have higher growth performance and production of eggs [63]. The reason may be that HSP70 enhances antioxidant status and growth performance and prevents lipid peroxidation in broiler chickens subjected to thermal stress [23]. Cells that possess elevated levels of HSP70 demonstrate enhanced resistance to heat by suppressing the formation of harmful oxygen-free radicals, diminishing the expression of death receptors and decreasing mitochondrial cascade signals. Consequently, they effectively prevent cell death triggered by heat-induced stress [64]. Moreover, HSP70 is involved in several physiological functions in the ovary, including cell growth, programmed cell death and hormonal pathways. This molecular chaperone participates in steroid signal transduction initiated by the estrogen nucleus and negatively regulates the expression of genes associated with ovarian development [65]. Laying poultry granulosa and theca cells that produce sex steroids are strongly associated with higher HSP70 expression under heat stress [66]. Additionally, HSP70 levels in small yellow follicles of broiler chickens in Taiwan are elevated due to intense heat stress. These responses could potentially serve as a vital protective mechanism. They help preserve follicle cells’ integrity and survival, ensuring an ample supply of small yellow follicles. This, in turn, ensures a successful ovulation selection and ultimately leads to successful egg production [67]. Thus, it is imperative to identify and use thermotolerant genotypes to maximize livestock productivity and reproduction. Figure 1 summarized the elevated HSP70 expression and livestock performance under heat stress.

Figure 1: Elevated HSP70 expression and livestock performance under heat stress. ↑, increase, ↓ decrease

4. Conclusions and future direction

Many types of HSPs are classified according to their molecular weight and act to protect the cells from various stresses. The HSP70 is one of the most crucial HSPs that protects cells from stress by preventing or mitigating damage to essential proteins and facilitating the continuation of protein regeneration. Furthermore, HSP70 plays a critical role in improving animal performance. Improving livestock productivity and reproduction requires identifying and exploiting thermotolerant genotypes. Therefore, highlighting the importance of HSP 70 is valuable for increasing livestock performance, and further molecular studies are needed for a better understanding of the effects of these proteins.

References
 
© 2023 The Uniited Graduate Schools of Agricultural Sciences, Japan
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