Propofol induces the elevation of intracellular calcium via morphological changes in intracellular organelles, including the endoplasmic reticulum and mitochondria

mitochondria- and ER-medicated pathways in neonatal rat cardiomyocytes.

Apoptosis : Int. J. Program. Cell Death 22, 639–646.

Miyahara, T., Adachi, N., Seki, T., Hide, I., Tanaka, S., Saito, N., Irifune, M., Sakai, N.,

2018. Propofol induced diverse and subtype-specific translocation of PKC families.

J. Pharmacol. Sci. 137, 20–29.

Nakajima, A., Tsuji, M., Inagaki, M., Tamura, Y., Kato, M., Niiya, A., Usui, Y., Oguchi, K.,

2014. Neuroprotective effects of propofol on ER stress-mediated apoptosis in

neuroblastoma SH-SY5Y cells. Eur. J. Pharmacol. 725, 47–54.

Nishimoto, R., Kashio, M., Tominaga, M., 2015. Propofol-induced pain sensation

involves multiple mechanisms in sensory neurons. Pflueg. Arch. Eur. J. Physiol. 467,

2011–2020.

Nobukuni, M., Mochizuki, H., Okada, S., Kameyama, N., Tanaka, A., Yamamoto, H.,

Amano, T., Seki, T., Sakai, N., 2009. The C-terminal region of serotonin transporter is

important for its trafficking and glycosylation. J. Pharmacol. Sci. 111, 392–404.

Partovian, C., Zhuang, Z., Moodie, K., Lin, M., Ouchi, N., Sessa, W.C., Walsh, K.,

Simons, M., 2005. PKCalpha activates eNOS and increases arterial blood flow in

vivo. Circ. Res. 97, 482–487.

Qiao, H., Li, Y., Xu, Z., Li, W., Fu, Z., Wang, Y., King, A., Wei, H., 2017. Propofol affects

neurodegeneration and neurogenesis by regulation of autophagy via effects on

intracellular calcium homeostasis. Anesthesiology 127, 490–501.

Subramanian, K., Meyer, T., 1997. Calcium-induced restructuring of nuclear envelope

and endoplasmic reticulum calcium stores. Cell 89, 963–971.

Sumi, C., Okamoto, A., Tanaka, H., Nishi, K., Kusunoki, M., Shoji, T., Uba, T., Matsuo, Y.,

Adachi, T., Hayashi, J.I., Takenaga, K., Hirota, K., 2018. Propofol induces a

metabolic switch to glycolysis and cell death in a mitochondrial electron transport

chain-dependent manner. PloS One 13, e0192796.

Sun, B., Ou, H., Ren, F., Huan, Y., Zhong, T., Gao, M., Cai, H., 2018. Propofol inhibited

autophagy through Ca(2þ)/CaMKKbeta/AMPK/mTOR pathway in OGD/R-induced

neuron injury. Mol. Med. 24, 58.

Tsuchiya, H., Ueno, T., Tanaka, T., Matsuura, N., Mizogami, M., 2010. Comparative

study on determination of antioxidant and membrane activities of propofol and its

related compounds. Eur. J. Pharmaceut. Sci. : Off. J. Eur. Fed. Pharmaceut. Sci. 39,

97–102.

Vasile, B., Rasulo, F., Candiani, A., Latronico, N., 2003. The pathophysiology of propofol

infusion syndrome: a simple name for a complex syndrome. Intensive Care Med. 29,

1417–1425.

Velly, L.J., Guillet, B.A., Masmejean, F.M., Nieoullon, A.L., Bruder, N.J., Gouin, F.M.,

Pisano, P.M., 2003. Neuroprotective effects of propofol in a model of ischemic

cortical cell cultures: role of glutamate and its transporters. Anesthesiology 99,

368–375.

Vollmer, J.P., Haen, S., Wolburg, H., Lehmann, R., Steiner, J., Reddersen, S., Fend, F.,

Fallier-Becker, P., 2018. Propofol related infusion syndrome: ultrastructural

evidence for a mitochondrial disorder. Crit. Care Med. 46, e91–e94.

Wang, H., Zheng, S., Liu, M., Jia, C., Wang, S., Wang, X., Xue, S., Guo, Y., 2016. The

effect of propofol on mitochondrial fission during oxygen-glucose deprivation and

reperfusion injury in rat hippocampal neurons. PloS One 11, e0165052.

Wang, L., Wu, B., Sun, Y., Xu, T., Zhang, X., Zhou, M., Jiang, W., 2010. Translocation of

protein kinase C isoforms is involved in propofol-induced endothelial nitric oxide

synthase activation. Br. J. Anaesth. 104, 606–612.

Yang, M., Wang, Y., Liang, G., Xu, Z., Chu, C.T., Wei, H., 2019. Alzheimer’s disease

presenilin-1 mutation sensitizes neurons to impaired autophagy flux and propofol

neurotoxicity: role of calcium dysregulation. J. Alzheim. Dis. : JAD 67, 137–147.

Zhou, X., Wei, Y., Qiu, S., Xu, Y., Zhang, T., Zhang, S., 2016. Propofol decreases

endoplasmic reticulum stress-mediated apoptosis in retinal pigment epithelial cells.

PloS One 11, e0157590.

Alkire, M.T., Hudetz, A.G., Tononi, G., 2008. Consciousness and anesthesia. Science 322,

876–880.

Asano, M., Motoike, S., Yokota, C., Usuki, N., Yamamoto, H., Urabe, T., Katarao, K.,

Hide, I., Tanaka, S., Kawamoto, M., Irifune, M., Sakai, N., 2019. SKF-10047, a

prototype Sigma-1 receptor agonist, augmented the membrane trafficking and

uptake activity of the serotonin transporter and its C-terminus-deleted mutant via a

Sigma-1 receptor-independent mechanism. J. Pharmacol. Sci. 139, 29–36.

Cox, C.E., Reed, S.D., Govert, J.A., Rodgers, J.E., Campbell-Bright, S., Kress, J.P.,

Carson, S.S., 2008. Economic evaluation of propofol and lorazepam for critically ill

patients undergoing mechanical ventilation. Crit. Care Med. 36, 706–714.

Felix, L.M., Correia, F., Pinto, P.A., Campos, S.P., Fernandes, T., Videira, R., Oliveira, M.

M., Peixoto, F.P., Antunes, L.M., 2017. Propofol affinity to mitochondrial

membranes does not alter mitochondrial function. Eur. J. Pharmacol. 803, 48–56.

Finsterer, J., Frank, M., 2016. Propofol is mitochondrion-toxic and may unmask a

mitochondrial disorder. J. Child Neurol. 31, 1489–1494.

Fleming, I., Fisslthaler, B., Dimmeler, S., Kemp, B.E., Busse, R., 2001. Phosphorylation of

Thr(495) regulates Ca(2þ)/calmodulin-dependent endothelial nitric oxide synthase

activity. Circ. Res. 88, E68–E75.

Franks, N.P., 2006. Molecular targets underlying general anaesthesia. Br. J. Pharmacol.

147 (Suppl. 1), S72–S81.

Gao, J., Peng, S., Xiang, S., Huang, J., Chen, P., 2014. Repeated exposure to propofol

impairs spatial learning, inhibits LTP and reduces CaMKIIalpha in young rats.

Neurosci. Lett. 560, 62–66.

Han, L., Fuqua, S., Li, Q., Zhu, L., Hao, X., Li, A., Gupta, S., Sandhu, R., Lonart, G.,

Sugita, S., 2016. Propofol-induced inhibition of catecholamine release is reversed by

maintaining calcium influx. Anesthesiology 124, 878–884.

Hemphill, S., McMenamin, L., Bellamy, M.C., Hopkins, P.M., 2019. Propofol infusion

syndrome: a structured literature review and analysis of published case reports. Br. J.

Anaesth. 122, 448–459.

Irifune, M., Takarada, T., Shimizu, Y., Endo, C., Katayama, S., Dohi, T., Kawahara, M.,

2003. Propofol-induced anesthesia in mice is mediated by gamma-aminobutyric

acid-A and excitatory amino acid receptors. Anesth. Analg. 97, 424–429 table of

contents.

Kirkpatrick, T., Cockshott, I.D., Douglas, E.J., Nimmo, W.S., 1988. Pharmacokinetics of

propofol (diprivan) in elderly patients. Br. J. Anaesth. 60, 146–150.

Kotani, Y., Shimazawa, M., Yoshimura, S., Iwama, T., Hara, H., 2008. The experimental

and clinical pharmacology of propofol, an anesthetic agent with neuroprotective

properties. CNS Neurosci. Ther. 14, 95–106.

Lawton, B.K., Brown, N.J., Reilly, C.S., Brookes, Z.L., 2012. Role of L-type calcium

channels in altered microvascular responses to propofol in hypertension. Br. J.

Anaesth. 108, 929–935.

Li, X., Yao, L., Liang, Q., Qu, H., Cai, H., 2018. Propofol protects hippocampal neurons

from hypoxia-reoxygenation injury by decreasing calcineurin-induced calcium

overload and activating YAP signaling. Oxid. Med. Cell. Longevity 2018, 1725191.

Liang, W.Z., Jan, C.R., Lu, C.H., 2012. Investigation of 2,6-diisopropylphenol (propofol)evoked Ca2þ movement and cell death in human glioblastoma cells. Toxicol. Vitro :

an international journal published in association with BIBRA 26, 862–871.

Liu, Q.Z., Hao, M., Zhou, Z.Y., Ge, J.L., Wu, Y.C., Zhao, L.L., Wu, X., Feng, Y., Gao, H.,

Li, S., Xue, L., 2019. Propofol reduces synaptic strength by inhibiting sodium and

calcium channels at nerve terminals. Protein Cell 10, 688–693.

Liu, X.R., Cao, L., Li, T., Chen, L.L., Yu, Y.Y., Huang, W.J., Liu, L., Tan, X.Q., 2017.

Propofol attenuates H2O2-induced oxidative stress and apoptosis via the

10

...