Fig. 1: Cacna1c downregulation preserved mitochondrial function in glutamate-challenged neuronal HT22 cells. | Cell Death & Disease

Fig. 1: Cacna1c downregulation preserved mitochondrial function in glutamate-challenged neuronal HT22 cells.

From: Psychiatric risk gene Cacna1c determines mitochondrial resilience against oxidative stress in neurons

Fig. 1

As mouse hippocampal HT22 cells do not express functional ionotropic glutamate receptors, glutamate toxicity is mediated via an oxidative stress-dependent pathway, including inhibition of the glutamate/cystine antiporter, a subsequent depletion of glutathione and a consecutive impairment of mitochondrial function, which ultimately leads to neuronal cell death (left panel). This glutamate-induced cascade is positively affected by Cacna1c knockdown (siRNA) and pharmacological LTCC inhibition (Nimodipine), which both mediate substantial protective effects on lipid peroxidation, mitochondrial integrity and function, and cell viability (right panel). XC−, glutamate/cystine antiporter; CaV1.2, voltage-gated l-type calcium channel; MCU, mitochondrial calcium uniporter; ROS, reactive oxygen species; ΔΨm, mitochondrial membrane potential; ATP, adenosine triphosphate

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