Changes in mitochondrial cytochrome c oxidase mRNA levels with cataract severity in lens epithelia of Japanese patients

Nagai,Noriaki; Mano,Yu; Otake,Hiroko; Shibata,Teppei; Kubo,Eri; Sasaki,Hiroshi

doi:10.3892/mmr.2019.10214

Changes in mitochondrial cytochrome c oxidase mRNA levels with cataract severity in lens epithelia of Japanese patients

Authors:
- Noriaki Nagai
- Yu Mano
- Hiroko Otake
- Teppei Shibata
- Eri Kubo
- Hiroshi Sasaki
View Affiliations

Affiliations: Department of Pharmacy, Kindai University, Higashi‑Osaka, Osaka 577‑8502, Japan, Department of Ophthalmology, Kanazawa Medical University, Kanazawa, Ishikawa 920‑0293, Japan
Published online on: May 2, 2019 https://doi.org/10.3892/mmr.2019.10214
Pages: 5464-5472

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

We previously reported that the collapse of ATP production via mitochondrial damage causes ATPase dysfunction, resulting in the onset or progression of lens opacification in cataracts in model rats. In the present study, it was investigated whether the mRNA expression levels of the three subtypes of mitochondrial cytochrome c oxidase (MTCO)1, 2 and 3 and ATP content change with the type and severity of cataracts in human lens. Samples of lens epithelium were collected from Japanese patients during cataract surgery, and the type and severity of the cataracts (grade) were determined according to the WHO classification [cortical (COR), nuclear (NUC), posterior subcapsular (PSC) opacification]. The MTCO1‑3 mRNA expression levels in patients with grade‑1 COR, NUC and PSC opacification were significantly enhanced compared with those of normal patients. The enhanced MTCO1‑3 mRNA levels subsequently decreased in patients with COR, and the MTCO1‑3 mRNA levels and ATP levels in patients with grade‑3 COR were similar to those in normal patients. However, the mRNA expression levels of MTCO3 in patients with grade 3‑NUC opacification and MTCO1‑3 in patients with grade‑3 PSC opacification, along with the ATP content, were significantly lower than in patients without cataracts. In conclusion, it was revealed that ATP production in lens epithelium is enhanced in early‑stage cataracts (grade‑1) in Japanese patients with COR, NUC and PSC opacification. In addition, in severe cataracts (grade‑3), ATP production and content are strongly decreased in Japanese patients with PSC opacification. ATP depletion in human lens epithelium with PSC opacification may promote lens opacification by ATPase dysfunction.

View Figures

View References

1	Angra SK, Murthy GV, Gupta SK and Angra V: Cataract related blindness in India & its social implications. Indian J Med Res. 106:312–324. 1997.PubMed/NCBI
2	Ezegwui IR, Aghaji AE, Uche NJ and Onwasigwe EN: Challenges in the management of paediatric cataract in a developing country. Int J Ophthalmol. 4:66–68. 2011.PubMed/NCBI
3	Furtado JM, Lansingh VC, Carter MJ, Milanese MF, Peña BN, Ghersi HA, Bote PL, Nano ME and Silva JC: Causes of blindness and visual impairment in Latin America. Surv Ophthalmol. 57:149–177. 2012. View Article : Google Scholar : PubMed/NCBI
4	Leske MC, Chylack LT Jr and Wu SY: The lens opacities case-control study. Risk factors for cataract. Arch Ophthalmol. 109:244–251. 1991. View Article : Google Scholar : PubMed/NCBI
5	Hammond CJ, Snieder H, Spector TD and Gilbert CE: Genetic and environmental factors in age-related nuclear cataracts in monozygotic and dizygotic twins. N Engl J Med. 342:1786–1790. 2000. View Article : Google Scholar : PubMed/NCBI
6	Iyengar SK, Klein BE, Klein R, Jun G, Schick JH, Millard C, Liptak R, Russo K, Lee KE and Elston RC: Identification of a major locus for age-related cortical cataract on chromosome 6p12-q12 in the beaver dam eye study. Proc Natl Acad Sci USA. 101:14485–14490. 2004. View Article : Google Scholar : PubMed/NCBI
7	Duncan G and Bushell AR: Ion analyses of human cataractous lenses. Exp Eye Res. 20:223–230. 1975. View Article : Google Scholar : PubMed/NCBI
8	Maraini G and Mangili R: Differences in protein and in the water balance of the lens in nuclear and cortical types of senile cataract. The Human Lens in Relation to Cataract. CIBA Foundation Symposium. Elliott K and Fitzsimons DW: Elsevier; Amsterdam, Netherlands: pp. 79–95. 1973
9	Patmore L and Duncan G: The physiology of lens membranes. Mechanisms of Cataract Formation in the Human Lens. Duncan G: Academic Press; London, England: pp. 193–217. 1981
10	Davies PD, Duncan G, Pynsent PB, Arber DL and Lucas VA: Aqueous humour glucose concentration in cataract patients and its effect on the lens. Exp Eye Res. 39:605–609. 1984. View Article : Google Scholar : PubMed/NCBI
11	Iwata S and Takehana N: Biochemical studies on human cataract lens. II. Opacity-related changes of cations, ATP and GSH in various types of human senile cataracts. Yakugaku Zasshi. 102:940–945. 1982.(In Japanese). View Article : Google Scholar : PubMed/NCBI
12	Gupta PD, Johar K and Vasavada A: Causative and preventive action of calcium in cataracto-genesis. Acta Pharmacol Sin. 25:1250–1256. 2004.PubMed/NCBI
13	Iwata S: Crystalline Lens. Suishotai, in Japanease. Iwata S: Medical-Aoi Publication Press; Tokyo, Japan: pp. 355–360. 1986
14	Nagai N, Ito Y and Takeuchi N: Inhibitive effects of enhanced lipid peroxidation on Ca(2+)-ATPase in lenses of hereditary cataract ICR/f rats. Toxicology. 247:139–144. 2008. View Article : Google Scholar : PubMed/NCBI
15	Blaustein MP: Endogenous ouabain: Role in the pathogenesis of hypertension. Kidney Int. 49:1748–1753. 1996. View Article : Google Scholar : PubMed/NCBI
16	Beebe DC, Holekamp NM and Shui YB: Oxidative damage and the prevention of age-related cataracts. Ophthalmic Res. 44:155–165. 2010. View Article : Google Scholar : PubMed/NCBI
17	Nagai N, Ito Y, Takeuchi N Usui S and Hirano K: Comparison of the mechanisms of cataract development involving differences in Ca(2+) regulation in lenses among three hereditary cataract model rats. Biol Pharm Bull. 31:1990–1995. 2008. View Article : Google Scholar : PubMed/NCBI
18	Nagai N and Ito Y: Adverse effects of excessive nitric oxide on cytochrome c oxidase in lenses of hereditary cataract UPL rats. Toxicology. 242:7–15. 2007. View Article : Google Scholar : PubMed/NCBI
19	Nagai N and Ito Y: Dysfunction in cytochrome c oxidase caused by excessive nitric oxide in human lens epithelial cells stimulated with interferon-γ and lipopolysaccharide. Curr Eye Res. 37:889–897. 2012. View Article : Google Scholar : PubMed/NCBI
20	Nabekura T, Tomohiro M, Ito Y and Kitagawa S: Changes in plasma membrane Ca2+ -ATPase expression and ATP content in lenses of hereditary cataract UPL rats. Toxicology. 197:177–183. 2004. View Article : Google Scholar : PubMed/NCBI
21	Liang HL, Ongwijitwat S and Wong-Riley MT: Bigenomic functional regulation of all 13 cytochrome c oxidase subunit transcripts in rat neurons in vitro and in vivo. Neuroscience. 140:177–190. 2006. View Article : Google Scholar : PubMed/NCBI
22	Thylefors B, Chylack LT Jr, Konyama K, Sasaki K, Sperduto R, Taylor HR and West S; WHO Cataract Grading Group, : A simplified cataract grading system. Ophthalmic Epidemiol. 9:83–95. 2002. View Article : Google Scholar : PubMed/NCBI
23	Nagai N, Ito Y, Shibata T, Kubo E and Sasaki H: A positive feedback loop between nitric oxide and amyloid β (1–42) accelerates mitochondrial damage in human lens epithelial cells. Toxicology. 381:19–30. 2017. View Article : Google Scholar : PubMed/NCBI
24	Kadenbach B, Jarausch J, Hartmann R and Merle P: Separation of mammalian cytochrome c oxidase into 13 polypeptides by a sodium dodecyl sulfate-gel electrophoretic procedure. Anal Biochem. 129:517–521. 1983. View Article : Google Scholar : PubMed/NCBI
25	Kuhn-Nentwig L and Kadenbach B: Isolation and properties of cytochrome c oxidase from rat liver and quantification of immunological differences between isozymes from various rat tissues with subunit-specific antisera. Eur J Biochem. 149:147–158. 1985. View Article : Google Scholar : PubMed/NCBI
26	Taanman JW: Human cytochrome c oxidase: Structure, function, and deficiency. J Bioenerg Biomembr. 29:151–163. 1997. View Article : Google Scholar : PubMed/NCBI
27	Lenka N, Vijayasarathy C, Mullick J and Avadhani NG: Structural organization and transcription regulation of nuclear genes encoding the mammalian cytochrome c oxidase complex. Prog Nucleic Acid Res Mol Biol. 61:309–344. 1998. View Article : Google Scholar : PubMed/NCBI
28	Livingston PM, Carson CA and Taylor HR: The epidemiology of cataract: A review of the literature. Ophthalmic Epidemiol. 2:151–164. 1995. View Article : Google Scholar : PubMed/NCBI
29	Shearer TR, David LL, Anderson RS and Azuma M: Reviewof selenite cataract. Curr Eye Res. 11:357–369. 1992. View Article : Google Scholar : PubMed/NCBI
30	Dilsiz N, Olcucu A and Atas M: Determination of calcium, sodium, potassium and magnesium concentrations in human senile cataractous lenses. Cell Biochem Funct. 18:259–262. 2000. View Article : Google Scholar : PubMed/NCBI
31	Shun Shin GA, Bron AJ, Brown NP and Sparrow JM: The relationship between central nuclear scatter and perinuclear retrodots in the human crystalline lens. Eye (Lond). 6:407–410. 1992. View Article : Google Scholar : PubMed/NCBI
32	Fariss MW, Chan CB, Patel M, Van Houten B and Orrenius S: Role of mitochondria in toxic oxidative stress. Mol Interv. 5:94–111. 2005. View Article : Google Scholar : PubMed/NCBI
33	Skou JC and Esmann M: Effects of ATP and protons on the Na: K selectivity of the (Na+ + K+)-ATPase studied by ligand effects on intrinsic and extrinsic fluorescence. Biochim Biophys Acta. 601:386–402. 1980. View Article : Google Scholar : PubMed/NCBI
34	Fu YF, Schuurmans Stekhoven FM, Swarts HG, de Pont JJ and Bonting SL: The locus of nucleotide specificity in the reaction mechanism of (Na+ + K+)-ATPase determined with ATP and GTP as substrates. Biochim Biophys Acta. 817:7–16. 1985. View Article : Google Scholar : PubMed/NCBI
35	Yang YC and Yingst DR: Effects of intracellular free Ca and rate of Ca influx on the Ca pump. Am J Physiol. 256:C1138–C1144. 1989. View Article : Google Scholar : PubMed/NCBI