Melatonin protects hippocampal HT22 cells from the effects of serum deprivation specifically targeting mitochondria

Abstract

Neurons contain a high number of mitochondria, these neuronal cells produce elevated levels of oxidative stress and live for a long time without proliferation; therefore, mitochondrial homeostasis is crucial to their health. Investigations have recently focused on mitochondrial dynamics revealing the ability of these organelles to change their distribution and morphology. It is known that mitochondrial fission is necessary for the transmission of mitochondria to daughter cells during mitosis and mitochondrial fragmentation has been used as an indicator of cell death and mitochondrial dysfunction. Oxidative stress is a trigger able to induce changes in the mitochondrial network. The aim of the present study was to determine the effects of melatonin on the mitochondrial network in HT22 serum-deprived cells. Our results showed that serum deprivation increased reactive oxygen species (ROS) content, promoted the activation of plasma membrane voltage-dependent anion channels (VDACs) and affected the expression of pDRP1 and DRP1 fission proteins. Moreover, parallel increases in apoptotic and autophagic features were found. Damaged and dysfunctional mitochondria are deleterious to the cell; hence, the degradation of such mitochondria through mitophagy is crucial to cell survival. Our results suggest that melatonin supplementation reduces cell death and restores mitochondrial function through the regulation of autophagy.

Novel Multifunctional Ascorbic Triazole Derivatives for Amyloidogenic Pathway Inhibition, Anti-Inflammation, and Neuroprotection

“…Serum is necessary for cell growth in cell culture systems because it contains essential growth elements. Therefore, when cultured cells are exposed to serum-deprivation conditions, this induces oxidative stress, leading to apoptosis [ 38 ]; this can be used as an in vitro model to assess neuroprotective activity. All ascorbic derivatives ( 2a – 2c and 5a – 5c ) showed significantly higher percentages of cell survival than that of 0.5% DMSO in the toxic conditions, which was the absence of fetal bovine serum (FBS; Figure 4 ; p < 0.05).…”

Reduction of Mitophagy-Related Oxidative Stress and Preservation of Mitochondria Function Using Melatonin Therapy in an HT22 Hippocampal Neuronal Cell Model of Glutamate-Induced Excitotoxicity

“…Mitophagy exerts a dual function; it promotes cell survival or death depending on the cellular context and microenvironment (54). The degradation of mitochondria via the mitophagy pathway is critical for cell survival under physiological conditions (55). However, hyperactivated mitophagy impairs mitochondrial function.…”

“…However, hyperactivated mitophagy impairs mitochondrial function. For example, Cesarini et al (55) showed that melatonin supplementation reduced cell death and restored mitochondrial function via autophagy regulation in hippocampal HT22 cells from the effects of serum deprivation. Feng et al (56) found that the myocardium was protected from ischemia/reperfusion injury via a reduction in mitochondrial dysfunction and mitophagy.…”

Calbindin regulates Kv4.1 trafficking and excitability of dentate granule cells via CaMKII-dependent phosphorylation

“…HT22 (Sigma-Aldrich #SCC129) and HEK293T (ATCC CRL-3216) cells were cultured as previously described (Cesarini et al, 2018;Pyun et al, 2018). HT22 and HEK293T cells were culture in DMEM medium containing 10% fetal bovine serum (FBS, Gibco) and transiently transfected with a combination of DNA plasmids by using lipofectamine 3000 (Invitrogen).…”