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Specific intracellular Ca2+ signal in hepatocytes after 70% partial hepatectomy in rats

Zenei Taira

Institute for Foods & Kampo Medicines, 1443 Kamihachimancho, Tokushima 770-8041, Japan

E-mail : bhuvaneswari.bibleraaj@uhsm.nhs.uk

Hiroshi Monmasu

Faculty of Pharmaceutical Sciences, Tokushima Bunri University, Tokushima, Japan

Yukari Ueda

Faculty of Pharmaceutical Sciences, Tokushima Bunri University, Tokushima, Japan

DOI: 10.15761/PMRR.1000221

Article
Article Info
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Key words

Partial hepatectomy, ratio of liver regeneration (Rr), intracellular Ca2+, S100A4, termination signal

Mini Review

New intracellular Ca2+ signal consisting of two successive peaks in hepatocytes is found during liver regeneration after 70% partial hepatectomy in rats [1,2].

1. That is, to study the regeneration mechanism of livers in male Donryu rats were subjected to the 70% PH method of Higgins and Anderson [3] at a scheduled time during 5:00 pm and 7:00 pm in Japan time, and the intracellular Ca2+ [Ca2+]i in hepatocytes was measured using a fluorescent Ca2+ indicator, fura-2 [4]. Hepatocytes (1×106 cells) were resuspended in 1 mL Ca2+- and Mg2+-free HBSS (pH 7.4) in a 10 mm quartz cuvette, and their fluorescence was measured at an emission wavelength of 500 nm and excitation of 340 or 380 nm using a spectrofluorometer. The proliferative phase restoring the liver volume after 70% PH were surrounding around a sustained increasing signal of [Ca2+]i in hepatocytes, consisting of two successive peaks with the first narrow peak at 1 hour and the second broad peak increasing by day 3 and then returning to normal by day 4. Then, the ratio (Rr) of the liver regeneration in rats after 70% PH was evaluated by the formula: Rr=100 × (total weight of the regenerated liver/total weight of the initially excised liver lobe pieces/0.7). Although the liver mass increased uniformly on the Rr curve after 70% PH and returned to the initial liver weight by day 10–14 except an abnormally high peak at around day 4 (P<0.05). Then, the Rr value had suddenly increased at around day 4 after 70% PH, temporarily exceeding 100%, and decreased steeply, followed by normal liver regeneration (P<0.05). Then, the Rr curve temporarily exceeded 100% and decreased steeply, followed by ordinary liver.

2. Various physiological activities after 70% PH were induced in response to promote liver regeneration. Indeed, susceptibility of hepatocytes against to cell death by intoxication switch from sensitivity to resistance between the two successive intracellular Ca2+ peaks, as confirmed in also low dose CCl4-induced liver injury, [5] and various physiological activities after 70% PH were induced to promote liver regeneration. Indeed, hepatocytes are resistant to intoxication for 2 days after 70% PH [6,7] and are the cytosolic Ca2+ increase [8]. The mRNA expression of genes encoding Ca2+-binding proteins S100A4 and calpain was increased by day 4, corresponding to the increase in Ca2+, and the hepatocytes proliferated synchronously. Thus, the number of cells in S phase increased strikingly with two divisions after 70% PH, hepatocytes underwent synchronous cell proliferation as the liver was restored from 30% to 70% at day 4, and significant expression of VEGF mRNA at around day 4 promoted angiogenesis to remodel the sinusoidal system. After the abnormal peak in the Rr curve occurred at day 4, liver regeneration was sustained in the Rr curve by liver swelling alone, as shown previously [9] and recovered transiently to the control level at day 4, returned to the decreased level, and then slowly recovered by day 10.

Conclusion

In conclusion, the increase in [Ca2+]i may be critical for the abnormal increase in Rr of liver regeneration at day 4 and the termination phase to complete liver regeneration after 70% PH. Even though, further study is in progress to precisely characterize the sustained increase in [Ca2+]i, consisting of two successive peaks. In this study, two novel signals were found that regulate liver regeneration after 70% PH in rats. The second finding was an abnormal and transient increase in the ratio Rr curve of liver regeneration at around day 4, and the two successive peaks [Ca2+]i signal.

Author contributions

All authors listed have made a substantial, direct and intellectual contribution to the work, and approved it for publication.

Disclosure

The authors report no conflicts of interest in this work.

References

  1. Taira Z, Ueda Y, Monmasu H, Yamase D, Miyake S, et al. (2016) Characteristics of intracellular Ca2+ signals consisting of two successive peaks in hepatocytes during liver regeneration after 70% partial hepatectomy in rats. J Exp Pharmacol 8: 21-33. [Crossref]
  2. Oliva-Vilarnau N, Hankeova S, Vorrink SU, Mkrtchian S, Andersson ER, et al. (2018) Calcium Signaling in Liver Injury and Regeneration. Front Med (Lausanne) 5: 192. [Crossref]
  3. Higgins GM, Anderson RM (1931) Restoration of the liver of the white rat following partial surgical removal. Arch Pathol 12: 186-202.
  4. Han AY, Zhang MH, Zuo XL, Zheng SS, Zhao CF, et al. (2010) Effect of acute heat stress on calcium concentration, proliferation, cell cycle, and interleukin-2 production in splenic lymphocytes from broiler chickens. Poult Sci 89: 2063-2070. [Crossref]
  5. Tachibana T, Kusumoto A, Ueda Y, Taira Z (2005) A cytoprotection of rat hepatocytes mediated by the intracellular calcium. J Hard Tissue Biol 14: 359-360.
  6. Thakore KN, Mehendale HM (1991) Role of hepatocellular regeneration in CCl4 autoprotection. Toxicol Pathol 19: 47-58. [Crossref]
  7. Collins F, Schmidt MF, Guthrie PB, Kater SB (1991) Sustained increase in intracellular calcium promotes neuronal survival. J Neurosci 11: 2582-2587. [Crossref]
  8. Roberts E, Ahluwalia MB, Lee G, Chan C, Sarma DS, et al. (1983) Resistance to hepatotoxins acquired by hepatocytes during liver regeneration. Cancer Res 43: 28-34. [Crossref]
  9. Miyaoka Y, Ebato K, Kato H, Arakawa S, Shimizu S, et al. (2012) Hypertrophy and unconventional cell division of hepatocytes underlie liver regeneration. Curr Biol 22: 1166-1175. [Crossref]

Editorial Information

Editor-in-Chief

Martin Grabois
Baylor College of Medicine

Article Type

Mini Review

Publication history

Received: February 09, 2021
Accepted: February 15, 2021
Published: February 25, 2021

Copyright

©2021 Taira Z. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Citation

Taira Z, Monmasu H, Ueda Y (2021) Specific intracellular Ca2+ signal in hepatocytes after 70% partial hepatectomy in rats. Phys Med Rehabil Res. 6. DOI: 10.15761/PMRR.1000221

Corresponding author

Zenei Taira

Institute for Foods & Kampo Medicines, 1443 Kamihachimancho, Tokushima 770-8041, Japan

E-mail : bhuvaneswari.bibleraaj@uhsm.nhs.uk

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