ASSOCIATIONS OF BIOCHEMICAL CHANGES AND MATERNAL TRAITS WITH MUTATION 1843 (C>T) IN THE RYR1 GENE AS A COMMON CAUSE FOR PORCINE STRESS SYNDROME
Popovski ZT, Tanaskovska B, Miskoska-Milevska E, Andonov S, Domazetovska S
*Corresponding Author: Professor Zoran T. Popovski, Ph.D., Faculty of Agriculture and Food Sciences, Bld “Aleksandar Makedonski,” bb PB 297, 1000 Skopje, Republic of Macedonia. Tel: +389-70-252-731. Fax: +389-2-3134-310. E-mail: zoran_popovski@yahoo.com
page: 75

INTRODUCTION

Porcine stress syndrome (PSS) is a hypermetabolic and hypercontractile syndrome triggered by anesthesia or various stressors that cause a sustained increase in sarcoplasmic calcium ion (Ca2+) [1]. The main consequence of PSS in humans and swine is the appearance of malignant hyperthermia (MH). Susceptibility to PSS is inherited as an autosomal dominant disease. Human MH is a lifethreatening, acute pharmacogenetic disorder of the skeletal muscle cells. Its manifestations are normally silent and only made evident when susceptible patients receive general anesthesia with volatile anesthetic agents or succinyldicholine [2]. The ryanodine receptor gene (ryr1) is the primary locus for stress susceptibility, but also other genes may be involved [3,4]. Predominantly, stress susceptibility in humans has been linked to the ryr1 gene and four other loci related to skeletal muscle excitation contraction coupling [2]. Most of the families with a familial history of stress syndrome have linkage to one of 175 mutations within ryr1 located on 19q13.1 [5]. Most frequent is a G>T transition mutation that results in the replacement of a conserved arginine at position 614 by leucine. A similar mutation occurs at position 1843 (C>T) resulting in replacement of arginine by cystine at position 615 in the swine genome in the ryr1 gene at locus 6p11-q21 [6]. Malignant hyperthermia occurs infrequently in humans (about one in 50,000), but PSS is common in pigs [7,8]. The similarity of the human and swine ryr1 gene is 91.2%. How this mutation affects the function in myotubes is not understood [9], but recent studies have shown that mutations in the ryr1 gene alter bidirectional signalling between 6,7-dihydropyeridine reductase (DHPR) and ryr1, even in the absence of triggering agents [10]. Malignant hyperthermia exhibits a hypermetabolic response with the release of lactic acid, potassium, and proteins (e.g., myoglobin and enzymes) from muscle cells. Their release accompanied with massive increase of blood catecholamines can result in death [1]. The pathophysiology of the crisis involves an uncontrolled release of cytoplasmic free calcium from the sarcoplasmic reticulum, leading to activation of energy-producing biochemical pathways [3]. In individuals susceptible to stress, it is generally accepted that increased level of either sarcoplasmic or myofibrillar-free calcium is the biochemical cause of the syndrome [11]. Thus, the main biochemical expression of PSS is intracellular deficit of Ca2+ that is mainly stored in terminal cisternae of sarcoplasmic reticulum where it is bound to the calcium-binding protein calsequestrin [12]. Total plasma calcium concentrations increase during a PSS crisis. Sarcoplasmic proteins also leak from muscle fibers during an acute episode. For instance, it is well-known that myoglobin, which has a low molecular weight (ca. 16,000 Da), leaks into the circulation, resulting in myoglobinemia [13]. The conversion of lactate, alanine and aspartate to glucose and oxidation of each to carbon dioxide (CO2), are processes that can be influenced by PSS [14]. Also, the stress causes a depletion of adenosine triphosphate (ATP) and extensive glycolysis in muscles [15], which can affect the activity of alkaline phosphatase (AP) responsible for removing the phosphate groups from several molecules, including nucleotides. Another interesting parameter closely related to ATP conversion is creatine phospho-kinase (CPK) that is associated with PSS [16]. It was suggested that fewer proteins are catabolized during the alanine cycle in stress-susceptible pigs; thus, total proteins were also included in this study [14]. Regarding that fact the accumulation of degradation metabolites (creatinine and bilirubin) generated by increased metabolic activity could be expected as possible biochemical markers of MH. The effects of PSS have been investigated on maternal performances. Heterozygous PSS (Nn) females farrowed more pigs in first pig birth than normal (NN) and homozygous (nn) females. The proportion of pigs born alive that survived was not different between females of differing PSS genotypes. Normal and Nn females had nearly identical adjusted number of live-born piglets [17]. The goal of this study was to determine the differences in nine biochemical parameters associated with PSS genotypes, and matching the PSS genotype with maternal traits in selected sows.



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