Archives

  • 2018-07
  • 2019-04
  • 2019-05
  • 2019-06
  • 2019-07
  • 2019-08
  • 2019-09
  • 2019-10
  • 2019-11
  • 2019-12
  • 2020-01
  • 2020-02
  • 2020-03
  • 2020-04
  • 2020-05
  • 2020-06
  • 2020-07
  • 2020-08
  • 2020-09
  • 2020-10
  • 2020-11
  • 2020-12
  • 2021-01
  • 2021-02
  • 2021-03
  • 2021-04
  • 2021-05
  • 2021-06
  • 2021-07
  • 2021-08
  • 2021-09
  • 2021-10
  • 2021-11
  • 2021-12
  • 2022-01
  • 2022-02
  • 2022-03
  • 2022-04
  • 2022-05
  • 2022-06
  • 2022-07
  • 2022-08
  • 2022-09
  • 2022-10
  • 2022-11
  • 2022-12
  • 2023-01
  • 2023-02
  • 2023-03
  • 2023-04
  • 2023-05
  • 2023-06
  • 2023-08
  • 2023-09
  • 2023-10
  • 2023-11
  • 2023-12
  • 2024-01
  • 2024-02
  • 2024-03
  • 2024-04

    • Researchers demonstrated that mitochondria are the main prod

    2022-11-18

    Researchers demonstrated that mitochondria are the main producers of ROS and are the most sensitive to the effects of ROS. Mitochondria-mediated apoptosis may not be limited to the role of cytochrome c in the activation of caspase-3 and ROS may provide an alternate mitochondrial signaling pathway (Houstis, Rosen & Lander, 2006). The generation of ROS is an inevitable event that can be significantly enhanced by functional impairment of the mitochondrial membrane. Our studies revealed that the cellular ROS content decreased from 0 h to 6 h but significantly increased from 6 h to 168 h during postmortem aging. The decrease in the ROS level at 6 h may be related to the presence of antioxidant enzymes in muscle cells. Glutathione redox system and superoxide dismutase in the cell sap can partially remove ROS during the early postmortem period. With intracellular environment deterioration, antioxidant enzyme activities are decreased and the redox system is broken, thereby leading to ROS accumulation in Cyprodime hydrochloride (Wedgwood, Dettman & Black, 2001). Therefore, we reasoned that ROS generation might be due to increased oxidative stress caused by postmortem aging. Cai, Yang & Jones (1998) showed that AIF release and inhibitor treatment of cells result in stimulated mitochondrial generation of ROS. Meanwhile, Ricci, Gottlieb & Green (2003) concluded that after outer mitochondrial membrane permeabilization and AIF release, activated caspases might target the permeabilized mitochondria. This result alters mitochondrial functional activity and generates ROS through the effects of caspases on complexes I and II in the electron transport chain. As a result, the generation of ROS is initiated, leading to AIF release. Recent observations have proposed the importance of Ca2+ concentration under apoptotic conditions. Ca2+ is one of the key regulators that control cell survival or apoptosis. Along with further research on Ca2+ and apoptosis, Ca2+ has been established as a fundamental cellular messenger and considered a trigger of apoptosis under cellular calcium overload conditions (Orrenius, Zhivotovsky & Nicotera, 2003). To elucidate how cellular Ca2+ affect AIF release during postmortem bovine aging of apoptosis, observation of cellular Ca2+ concentration after apoptotic stimulation is absolutely necessary. Therefore, an increase in cellular Ca2+ concentration was observed in this study. Postmortem aging can result in a depression in the sarcolemmal Ca2+ – pump ATPase and Na+ – K+ ATPase activities, leading to decreased Ca2+ – efflux and increased Ca2+ – influx (Jing et al., 2012). Subsequently, the opening of mitochondrial membrane permeability transition pore increased with the accumulation of cellular Ca2+, mitochondrial membrane swelling and AIF released from mitochondria to nuclei. In addition, the increase in cellular Ca2+ concentration can alter the membrane phospholipid concentrations and induce a calcium homeostasis disorder. Daugas et al., 2000, Daugas et al., 2000 showed that AIF mediates cell apoptosis associated with an increased cellular Ca2+ concentration. The above evidence showed that cellular Ca2+ concentration indirectly influence the AIF release, that is, cellular Ca2+ concentration affects AIF release through acting on the mitochondrial membrane. Furthermore, the elevation of Ca2+ concentration could result in the activation of a series of Ca2+ – sensitive enzymes to initiate apoptosis (Sharma & Rohrer, 2004). We primarily focused on the apoptotic pathway triggered by activated calpain I and cathepsins in this study. These enzymes produce signaling molecules for activating the caspase system and are directly connected to mitochondrial apoptotic proteins. Upon exposure to Ca2+ in cells, calpain I undergoes auto-cleavage and becomes active. At this time, the N-terminal amino acid of AIF in mitochondria becomes sensitive due to calpain I activation, wherein 62 kDa of AIF is cleavaged into mature 57 kDa of AIF with apoptotic activity and is released into cytoplasm and to nucleus, triggering apoptosis (Norberg, Gogvadze, Vakifahmetoglu, Orrenius & Zhivotovsky, 2010). Wang et al. (2017) demonstrated that Ca2+ concentration elevation acts as a pro-apoptotic signal, triggers calpain I, and induces cell apoptosis. Therefore, the AIF release might be influenced by activating of calpain I. Unfortunately, authors in this study did not investigate the effect of calpain I inhibitor on AIF release. Thus, the influence of calpain I on the release of AIF requires further study.