Interaction of exercise training with taurine attenuates infarct size and cardiac dysfunction via Akt–Foxo3a–Caspase-8 signaling pathway

Abstract

The purpose of this research was to investigate the synergistic protective effect of exercise training and taurine on Akt-Foxo3a-Caspase-8 signaling related to infarct size and cardiac dysfunction. 25 Male Wistar rats with MI were divided into ve groups sham (Sh), control-MI(C-MI), exercise training-MI(Exe-MI), taurine supplementation-MI(Supp-MI), exercise training + taurine-MI(Exe + Supp-MI). The taurine groups were given a 200 mg/kg/day dose of taurine by drinking water. Exercise training was conducted for 8 weeks (5d/wk), each session alternated 2 min with 25-30% VO2peak and 4 min with 55-60% VO2peak for 10 alternations. Then, the left ventricle tissue samples were taken from all groups. Exercise training and taurine activated Akt and decreased Foxo3a. Expression of the caspase-8 gene was increased in cardiac necrosis after MI, While, after 12 weeks of intervention decreased. Results exhibited that exercise training combined with taurine has a greater effect than either alone on activating the Akt-Foxo3acaspase signaling pathway (P < 0.001). MI-induced myocardial injury leads to increase collagen deposition (P < 0.001) and infarct size and results in cardiac dysfunction via reduced stroke volume, ejection fraction, and fractional shortening (P < 0.001). Exercise training and taurine improved cardiac function parameters (SV, EF, FS) and infarct size (P < 0.001) after 8 weeks of intervention in rats with MI. Also, the interaction of exercise training and taurine has a greater effect than alone on these variables. Interaction of exercise training with taurine supplementation induces a general amelioration of the cardiac histopathological pro les and improves cardiac remodeling via activating Akt-Foxo3a-Caspase-8 signaling with protective effects against MI.

Cognitive Impairment in Multiple Sclerosis

“…Given that mammalian forkhead transcription factors (FoxOs) can have an important relationship to cell death pathways during neurodegenerative disorders [2,5,49,259,260,[299][300][301][302][303][304], they are increasingly being recognized as potential therapeutic targets for MS (Figure 1). In particular, the mammalian FOXO proteins of the O class can lead to neuronal cell death through apoptosis and autophagy activation [5,49,50,68,128,203,250,301,[305][306][307][308][309][310][311][312][313][314][315]. Other studies suggest that the progressive course of MS may be associated with epigenetic changes of DNA methylation that are dependent upon genetic variations of FOXOs, such as FoxO1 and FoxO3a [128] (Table 1).…”

Cornerstone Cellular Pathways for Metabolic Disorders and Diabetes Mellitus: Non-Coding RNAs, Wnt Signaling, and AMPK

“…If the second phase of apoptotic cell death is reached, it is usually not reversible and involves the degradation of nuclear deoxyribonucleic acid (DNA) [136,137,167,169,[290][291][292][293][294]. The second stage of apoptosis consists of mitochondrial membrane depolarization, cytochrome c release, and caspase activation [136,193,252,290,[295][296][297][298][299][300]. Apoptosis during DM can lead to atherosclerotic plaque generation [296,301,302], foster processes associated with infection, such as COVID-19 [59,71,303,304], promote joint degenerative diseases [152,293,[305][306][307], and enhance stem cell demise and inflammatory pathway activation [26,103,129,132,291,[308][309][310][311][312][313][314].…”

“…In the absence of AMPK activity, cell senescence, cell death, and mitochondrial injury can ensue [3,137]. WISP1 controls the phosphorylation of AMPK by differentially limiting phosphorylation of tuberous sclerosis 2 (TSC2) at serine 1387 , a target of AMPK, and promoting phosphorylation of TSC2 at threonine 1462 , a target of Akt [103,300,310,345,396,490,501] that has been shown to mediate protection of pancreatic cells [502] and neuroprotection [60,455,503] through glucagon-like peptide-1 (GLP-1). This ability of WISP1 to target and control AMPK may improve cell survival and metabolic homeostasis [168] since AMPK at times can reduce oxidative stress, limit insulin resistance [369], and lower lipid accumulation [504].…”

The impact of aging and oxidative stress in metabolic and nervous system disorders: programmed cell death and molecular signal transduction crosstalk

“…Treatments directed to restore PS membrane asymmetry for injured cells can then prevent microglial attraction and preserve the function of these necessary cells in the nervous system (66, [511][512][513]. In contrast, the later phase of apoptotic cell death that consists of the destruction of nuclear deoxyribonucleic acid (DNA) (18, 96, 113, 229, 483, 514-518) and a cascade of caspase activation (65, 96, 130,143,347,348,405,425,483,519) is not reversible.…”

“…Microglia account for about fifteen percent of the cells in the central nervous system and as noted can remove injured cells during apoptosis (97, 120,133,134,152,155,425,430,502,503). These inflammatory cells can release ROS to generate oxidative stress (7,18,62,121,282,(526)(527)(528) through pathways that involve Wnt signaling (2, 6, 97, 122, 181, 529-531), mammalian forkhead transcription factors (17,67,68,117,426,519,532), and growth factors with EPO (6,145,159,482,(533)(534)(535)(536). During cognitive dysfunction, microglial activity may lead to increased risk for the development of AD (141, 537) as well as endothelial dysfunction (119).…”