PMID- 34597723 OWN - NLM STAT- MEDLINE DCOM- 20211222 LR - 20211222 IS - 1872-8006 (Electronic) IS - 0304-4165 (Linking) VI - 1865 IP - 12 DP - 2021 Dec TI - PACAP-derived mutant peptide MPAPO protects trigeminal ganglion cell and the retina from hypoxic injury through anti-oxidative stress, anti-apoptosis, and promoting axon regeneration. PG - 130018 LID - S0304-4165(21)00177-X [pii] LID - 10.1016/j.bbagen.2021.130018 [doi] AB - The purpose of this study was to determine whether the MPAPO, derived peptide of pituitary adenylate cyclase-activating polypeptide (PACAP), would protect trigeminal ganglion cells (TGCs) and the mice retinas from a hypoxic insult. The nerve endings of the ophthalmic nerve of the trigeminal nerve are widely distributed in eye tissues. In TGCs after hypoxia exposure, we discovered that reactive oxygen species level, the contents of cytosolic cytochrome c and cleaved-caspase-3 were significantly increased, in the meanwhile, m-Calpain was activated and cytoskeleton proteins (alphaII-spectrin and Synapsin) were degraded, neurites of TGCs disappeared, but these effects were reversed in TGCs treated with MPAPO. The structure of the mice retinas after hypoxic exposure was disordered. Increased lipid peroxidation (LPO), decreased glutathione (GSH) levels, and decreased superoxide dismutase (SOD) activity, positive cells of terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL), the disintegration of nerve fibers was examined in the retinas following a hypoxic insult. Disordered retina was attenuated with MPAPO eye drops, as well as hypoxia-induced apoptosis in the developing retina, increase in LPO, and decrease in GSH levels and SOD activity of the retina. Moreover, the disintegrated retinal nerve fibers were reassembled after MPAPO treatment. These results suggest that hypoxia induces oxidative stress, apoptosis, and neurites disruption, while MPAPO is remarkably protective against these adverse effects of hypoxia in TGCs and the developing retinas by specifically activating PAC1 receptor. CI - Copyright (c) 2021 Elsevier B.V. All rights reserved. FAU - Li, Hui-Xian AU - Li HX AD - Institute of Biomedicine, Department of Cellular Biology, National Engineering Research Center of Genetic Medicine, Key Laboratory of Bioengineering Medicine of Guangdong Province, The national Demonstration center for Experimental Education of Life Science and Technology, Jinan University, 601 Huangpu Ave West, Guangzhou, 510632, Guangdong, People's Republic of China. FAU - Feng, Jia AU - Feng J AD - Institute of Biomedicine, Department of Cellular Biology, National Engineering Research Center of Genetic Medicine, Key Laboratory of Bioengineering Medicine of Guangdong Province, The national Demonstration center for Experimental Education of Life Science and Technology, Jinan University, 601 Huangpu Ave West, Guangzhou, 510632, Guangdong, People's Republic of China. FAU - Liu, Qian AU - Liu Q AD - Institute of Biomedicine, Department of Cellular Biology, National Engineering Research Center of Genetic Medicine, Key Laboratory of Bioengineering Medicine of Guangdong Province, The national Demonstration center for Experimental Education of Life Science and Technology, Jinan University, 601 Huangpu Ave West, Guangzhou, 510632, Guangdong, People's Republic of China. FAU - Ou, Bi-Qian AU - Ou BQ AD - Institute of Biomedicine, Department of Cellular Biology, National Engineering Research Center of Genetic Medicine, Key Laboratory of Bioengineering Medicine of Guangdong Province, The national Demonstration center for Experimental Education of Life Science and Technology, Jinan University, 601 Huangpu Ave West, Guangzhou, 510632, Guangdong, People's Republic of China. FAU - Lu, Shi-Yin AU - Lu SY AD - Institute of Biomedicine, Department of Cellular Biology, National Engineering Research Center of Genetic Medicine, Key Laboratory of Bioengineering Medicine of Guangdong Province, The national Demonstration center for Experimental Education of Life Science and Technology, Jinan University, 601 Huangpu Ave West, Guangzhou, 510632, Guangdong, People's Republic of China. FAU - Ma, Yi AU - Ma Y AD - Institute of Biomedicine, Department of Cellular Biology, National Engineering Research Center of Genetic Medicine, Key Laboratory of Bioengineering Medicine of Guangdong Province, The national Demonstration center for Experimental Education of Life Science and Technology, Jinan University, 601 Huangpu Ave West, Guangzhou, 510632, Guangdong, People's Republic of China. Electronic address: tmayi@jnu.edu.cn. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20210928 PL - Netherlands TA - Biochim Biophys Acta Gen Subj JT - Biochimica et biophysica acta. General subjects JID - 101731726 RN - 0 (Pituitary Adenylate Cyclase-Activating Polypeptide) SB - IM MH - Axons MH - Nerve Regeneration MH - *Pituitary Adenylate Cyclase-Activating Polypeptide OTO - NOTNLM OT - Apoptosis OT - Axon regeneration OT - Oxidative stress OT - PAC1 receptor OT - PACAP-derived mutant peptide (MPAPO) OT - Repair of hypoxia-injured trigeminal ganglion cells and the retinas EDAT- 2021/10/02 06:00 MHDA- 2021/12/24 06:00 CRDT- 2021/10/01 20:15 PHST- 2021/01/07 00:00 [received] PHST- 2021/08/30 00:00 [revised] PHST- 2021/09/20 00:00 [accepted] PHST- 2021/10/02 06:00 [pubmed] PHST- 2021/12/24 06:00 [medline] PHST- 2021/10/01 20:15 [entrez] AID - S0304-4165(21)00177-X [pii] AID - 10.1016/j.bbagen.2021.130018 [doi] PST - ppublish SO - Biochim Biophys Acta Gen Subj. 2021 Dec;1865(12):130018. doi: 10.1016/j.bbagen.2021.130018. Epub 2021 Sep 28.